Klarskov, Louise; Holck, Susanne; Bernstein, Inge
BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...
Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history
Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.
Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within
Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM
Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of
Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.
... before 50). Dave has Lynch syndrome and had colorectal cancer at 28. Amy found out she has Lynch syndrome when she was diagnosed with colorectal cancer days after turning 47. Why is it Important ...
Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.
Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised
M. H. Sun
Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.
Wu, Y; Berends, MJW; Sijmons, RH; Mensink, RGJ; Verlind, E; Kooi, KA; van der Sluis, T; Kempinga, C; van der Zee, AGJ; Hollema, H; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW
We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations,
Full Text Available Introduction: Colorectal cancer (CRC is the third leading cause of cancer deaths in the world, and hereditary factors and family history are responsible for the incidence and development of the disease in 20 to 30% of cases. Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC, is the most common hereditary form of CRC that is inherited in an autosomal dominant manner. This study consisted of a systematic literature review of research articles that described the prevalence of HNPCC in Iranian patients with CRC. Methods: A systematic literature search was conducted in the PubMed, Scopus, IranMedex, and Google Scholar databases to identify relevant articles that describe HNPCC or Lynch syndrome in patients with CRC in Iran. For this purpose, a keyword search of the following terms was employed: (((Hereditary nonpolyposis colorectal cancer OR HNPCC OR Lynch syndrome AND (colorectal cancer OR familial colorectal cancer OR colon cancer OR rectal cancer OR bowel cancer AND IRAN. All eligible documents were collected, and the desired data were qualitatively analyzed.Result: Of the 67 articles that were found via the initial database search, only 12 were deemed to be of relevance to the current study. These articles included a total population of 3237 and this sample was selected and qualitatively analyzed. The findings of the review revealed that the frequency of mutation in MLH1, MSH2, PMS2, and MSH6 genes varied between 23.1% and 62.5% among the studied families. This indicated that HNPCC is linked with up to 5.5% of the total cases of colorectal cancers in Iran.Conclusion: The results of this study revealed that the hereditary form of HNPCC or Lynch syndrome is significantly high among patients with CRC in Iran
Diergaarde, B.; Braam, H.; Vasen, H.F.; Nagengast, F.M.; Muijen, van G.N.P.; Kok, F.J.; Kampman, E.
Background & Aims: Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) are at increased risk for colorectal cancer. Environmental factors might play a role in HNPCC-associated carcinogenesis. The aim of this study was to gain insight into the effects of environmental factors on
Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH
Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations
Vos tot Nederveen Cappel, W.H. de; Nagengast, F.M.; Griffioen, G.; Menko, F.H.; Taal, B.G.; Kleibeuker, J.H.; Vasen, H.F.
PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive
Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF
PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive
Vasen, H. F.; Offerhaus, G. J.; den Hartog Jager, F. C.; Menko, F. H.; Nagengast, F. M.; Griffioen, G.; van Hogezand, R. B.; Heintz, A. P.
The hereditary colonic cancer syndrome without polyposis, hereditary non-polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site-specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II).
Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.
Reyes, J; Ginard, D; Barranco, L; Escarda, A; Vanrell, M; Mariño, Z; Garau, I; Llompart, A; Gayà, J; Obrador, A
Identification of patients with hereditary nonpolyposis colorectal cancer (HNPCC) can allow colorectal cancer (CRC) prevention through colonoscopy and polypectomies. The purpose of this study was to report the clinical characteristics of HNPCC families in our registry. HNPCC was identified using the Amsterdam criteria. Familial clustering of CRC and extracolonic cancers were investigated in families. Individuals at risk were offered annual colonoscopy, starting from the age of 25 years. Twelve HNPCC families were identified. There were 46 cases of CRC in 38 patients. The mean age at diagnosis of CRC was 45.4 +/- 12.7 years (range 25-73 years). In patients with documented disease, right-sided tumors predominated. Eleven patients with extracolonic cancer were identified (six tumors located in the endometrium). Of 43 at-risk individuals, 29 accepted surveillance. Our data confirm the importance of the family history in identifying HNPCC. This study confirms previously described characteristics in HNPCC, namely, early age at onset of CRC, right-sided predominance, multiple synchronous and metachronous neoplasms, and increased extracolonic cancers. This is the first study of clinical data in a Spanish HNPCC registry.
Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie
Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...
Sijmons, RH; Kiemeney, LALM; Witjes, JA; Vasen, HFA
Purpose: We investigate the risk of the different types of urinary tract cancer in hereditary nonpolyposis colorectal cancer families and review screening options. Materials and Methods: We retrospectively calculated the relative and cumulative risks of developing urinary tract cancer by comparing
Berends, MJW; Wu, Y; Sijmons, RH; Hofstra, RMW; van der Zee, AGJ; Buys, CHCM; Kleibeuker, JH
Hereditary non-polyposis colorectal cancer is an autosomal dominant inherited disorder that predisposes its carriers to an almost 100% lifetime risk of cancer, in particular colorectal and endometrial cancer. Germline mutations, resulting in a deficient DNA mismatch repair system. are responsible
Garry N. Hannan
Full Text Available Hereditary non-polyposis colorectal cancer (HNPCC is the commonest form of inherited colorectal cancer (CRC predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.
Wang, Xu-Lin; Yuan, Ying; Zhang, Su-Zhan; Cai, Shan-Rong; Huang, Yan-Qin; Jiang, Qiang; Zheng, Shu
AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.
Domanska, K; Nilbert, Mef; Soller, M
to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1......Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10...... year prior to the study reported higher, albeit not significantly, perceived risks of colorectal cancer. Higher perceived risks were also reported by individuals who had lost a parent to HNPCC-related cancer at early age, whereas individuals with a personal history of cancer did not report a higher...
Domanska, K; Nilbert, Mef; Soller, M
Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10...... to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1...... year prior to the study reported higher, albeit not significantly, perceived risks of colorectal cancer. Higher perceived risks were also reported by individuals who had lost a parent to HNPCC-related cancer at early age, whereas individuals with a personal history of cancer did not report a higher...
Full Text Available Background: There is a lack of data on familial aggregation of colorectal cancer (CRC in Iran. We aimed to deter-mine the frequency of hereditary nonpolyposis colorectal cancer (HNPCC and familial colorectal cancer (FCC and to determine the frequency of extracolonic cancers in these families in Isfahan. Methods: We reviewed documents of all patients with a pathologically confirmed diagnosis of CRC admitted to Isfa-han referral hospitals between 1995 and 2006. We also studied our CRC registry at Poursina Hakim Research Institute from 2003 to 2008. We found HNPCC and FCC families based on the Amsterdam II criteria and interviewed them for family history of CRC and extracolonic tumors. The family history was taken at least up to the second-degree relatives. Results: During 1996 to 2008, a total of 2580 CRC cases have been diagnosed. We found 14 HNPCC and 53 FCC families. Mean age of CRC at diagnosis was 48.0 14.6 and 49.0 13.9 years in the HNPCC and FCC families, re-spectively (p > 0.05. The total numbers of observed extracolonic tumors were 70 (21.6%; mean age = 53.6 11.0 years and 157 (13.8%; mean age = 54.8 18.0 years in HNPCC and FCC families, respectively (p > 0.05. CRC was respectively found in 52 and 76 members of the HNPCC and FCC families, revealing the frequency of HNPCC and FCC as 2.0% (52/2580 and 2.9% (76/2580, respectively. Conclusions: We found a relative high frequency of HNPCC (2.0% and FCC (2.9% among CRC cases in our socie-ty and high incidence of extracolonic tumors in their families. Further studies focusing on molecular basis in this field and designing a specific screening and national cancer registry program for HNPCC and FCC families should be con-ducted.
Umar, Asad; Boland, C. Richard; Terdiman, Jonathan P.; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M.; Burgart, Lawrence J.; Hamelin, Richard; Hamilton, Stanley R.; Hiatt, Robert A.; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T.
Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to...
Domanska, Katarina; Carlsson, Christina; Bendahl, Pär-Ola
questions about cancer risks and surveillance strategies. RESULTS: Both groups answered questions on colorectal cancer risk, surveillance and genetic testing well, whereas answers about inheritance and risks for HNPCC associated cancer were less accurate. Only half of the family members and one third......BACKGROUND: Identification and adequate management of individuals at risk for hereditary nonpolyposis colorectal cancer (HNPCC) is crucial since surveillance programmes reduce morbidity and mortality. We investigated knowledge about key features of HNPCC in at risk individuals and physicians...
Chu Annie TW; Bonanno George A; Ho Judy WC; Ho Samuel MY; Chan Emily MS
Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer R...
Movahedi, Mohammad; Bishop, D Timothy; Macrae, Finlay
PURPOSE: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk...... was 25.0 months, and mean follow-up was 55.7 months. RESULTS: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg....../m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation...
Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen
BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients...... were compared with 870 patients with sporadic colorectal cancer. RESULTS: The median age at CRC diagnosis was 41 years in the HNPCC group. HNPCC patients had significantly more carcinomas located to the right colon (68% against 49% in controls), more synchromous tumours (7% versus 1%), more...
Rohlin, Anna; Rambech, Eva; Kvist, Anders
Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel...
The human DNA mismatch repair (MMR) system functions to repair mispaired bases in DNA that result from DNA replication errors and thereby prevents the accumulation of mutations due to such replication errors. Hereditary nonpolyposis colorectal cancer (HNPCC), the most common form of inherited colon
Ketabi, Zohreh; Gerdes, Anne-Marie; Mosgaard, Berit
Objective. We aimed to estimate the incidence rate of endometrial cancer (EC) and to evaluate the results of EC-surveillance in hereditary nonpolyposis colorectal cancer (HNPCC) families. Methods. All at-risk women recommended for EC-surveillance by the HNPCC-register-2959 women (19,334 women yea...... of having Lynch syndrome. We conclude that EC surveillance should only be targeted at MMR-mutation carriers. (C) 2014 Elsevier Inc. All rights reserved....
Full Text Available A disproportionately large number of young (<50 years black patients present with colorectal cancer (CRC in South Africa. Although a phenomenon previously described elsewhere in Africa, its specificmolecular basis,whether sporadic or hereditary, has not been established. Molecular analysis of these tumours could link them to the features known to be associated with specific types of hereditary colorectal cancer, specifically through examination of levels of microsatellite instability, promoter methylation and the presence or absence of KRAS and BRAF mutations. The molecular features of cancer tissue samples from 44 CRC cases of black and white patients in South Africa were accordingly retrospectively analysed without knowledge of family history. Compared with samples from older blacks (>50 years, those from young black patients presented more often with a low methylation phenotype (CIMP-L and high levels of microsatellite instability (MSI-H. Furthermore, as determined by real-time PCR using probe technology, the tissues from35%of young blacks showed mutations within exon 1 of the KRAS gene. The BRAF-V600E mutation was only evident in the case of a single young black patient. Based on these results it seems likely that a proportion of CRC cases in young black patients from South Africa develop through the accumulation of mutations resulting in a mismatch repair deficiency linked to MSI-H and, possibly, germline mutations in the mismatch repair genes. The features in these patients are consistent with a diagnosis of the Hereditary Non-Polyposis Colorectal Cancer (HNPCC syndrome. This finding has important implications for patient management and suggests that family members may be at high risk for CRC.
Full Text Available Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation.
Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC
Umar, Asad; Boland, C. Richard; Terdiman, Jonathan P.; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M.; Burgart, Lawrence J.; Hamelin, Richard; Hamilton, Stanley R.; Hiatt, Robert A.; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T.; Peltomaki, Païvi; Ramsey, Scott D.; Rodriguez-Bigas, Miguel A.; Vasen, Hans F. A.; Hawk, Ernest T.; Barrett, J. Carl; Freedman, Andrew N.; Srivastava, Sudhir
Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to the development of the Bethesda Guidelines for the identification of individuals with HNPCC who should be tested for MSI. To consider revision and improvement of the Bethesda Guidelines, another HNPCC workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In this commentary, we summarize the Workshop presentations on HNPCC and MSI testing; present the issues relating to the performance, sensitivity, and specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines for identifying individuals at risk for HNPCC; and recommend criteria for MSI testing. PMID:14970275
Hendriks, Yvonne M. C.; Wagner, Anja; Morreau, Hans; Menko, Fred; Stormorken, Astrid; Quehenberger, Franz; Sandkuijl, Lodewijk; Møller, Pal; Genuardi, Maurizio; van Houwelingen, Hans; Tops, Carli; van Puijenbroek, Marjo; Verkuijlen, Paul; Kenter, Gemma; van Mil, Anneke; Meijers-Heijboer, Hanne; Tan, Gita B.; Breuning, Martijn H.; Fodde, Riccardo; Wijnen, Juul Th; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans
BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20
Kravochuck, Sara E; Church, James M
Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.
Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola
Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC......). We specifically addressed anticipation in phenotypic HNPCC families without disease-predisposing mismatch repair (MMR) defects since risk estimates and age at onset are particularly difficult to determine in this cohort. The national Danish HNPCC register was used to identify families who fulfilled...... the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated...
Vasen, HFA; Stormorken, A; Menko, FH; Nagengast, FM; Kleibeuker, JH; Griffioen, G; Taal, BG; Moller, P; Wijnen, JT
Purpose: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and
Vasen, H.F.; Stormorken, A.; Menko, F.H.; Nagengast, F.M.; Kleibeuker, J.H.; Griffioen, G.; Taal, B.G.; Moller, P.; Wijnen, J.T.
PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and
Sarroca, C.; Della Valle, A.; Fresco, R.; Peltomaki, P.; Lynch, H.
Full text: Colonic Cancer Family Polipótic not (CCFNP) is a syndrome transmission autosomal dominant characterized by the aggregation of colorectal cancer (CCR), frequently associated with other solid tumors. Few studies have investigated CCFNP frequency in colorectal cancer patients. these have shown marked geographic variation (0.3% to 13%). The objective of this study is to estimate the frequency of a population CCFNP CCR carriers Uruguayan cancer patients. All patients consecutively operated CRC were included in the Hospital Central Armed Forces (Montevideo, Uruguay) between 1987 and 2003. The cases were classified into 3 groups: 1) those who met the criteria Amsterdam (CCFNP), 2) those who did not meet these criteria but considered as a population of increased risk of cancer based on family history / staff (PRI), and 3) sporadic CRC. Genetic analysis was performed for Detection of mutations in hMLH1, hMSH2 and hMSH6 gene in patients subgroup 1. 461 patients were included, with a median age of 66 years. The subgroup 1 represented 2.5% 2 5.6% and 91.8% sporadic CRC. 75% of cases CCFNP were classified as under 55. Mutations in hMLH1 / hMSH2/hMSH6 were found in 16.6% of cases included in the subgroup 1 (2 in hMLH1, 1 in hMSH2, hMSH6 none). The proportion of patients who met the Amsterdam criteria matches with that observed by other authors. However, the percentage of cases classified CCFNP identified as carriers of mutations is lower than that reported (16.6% vs. ~ 70%). This may reflect a different genetic profile Uruguayan population
Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based
Ekstrand, Anna Isinger; Jönsson, Mats; Lindblom, Annika
The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT......, and PTEN in colorectal cancers linked to hereditary nonpolyposis colorectal cancer (HNPCC). Sequencing was used to identify mutations in PIK3CA, a real-time PCR-based method to identify KRAS mutations, and immunohistochemical staining was used to evaluate the expression of PIK3CA, phosphorylated AKT...... and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59...
Full Text Available Over 1.900 colorectal tumors will arise in association with a hereditary colorectal cancer syndrome in Spain in 2009. The genetic defects responsible for the most common syndromes have been discovered in recent years. Genetic testing helps diagnose affected individuals and allows identification of individuals at-risk. Colonoscopy and prophylactic colectomy decrease colorectal cancer incidence and overall mortality in patients with hereditary colon cancer. Extracolonic tumors are frequent in these syndromes, so specific surveillance strategies should be offered.
... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...
Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study
Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won
PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...
de Jong, Andrea E.; van Puijenbroek, Marjo; Hendriks, Yvonne; Tops, Carli; Wijnen, Juul; Ausems, Margreet G. E. M.; Meijers-Heijboer, Hanne; Wagner, Anja; van Os, Theo A. M.; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans F. A.; Morreau, Hans
Immunohistochemistry (IHC) and microsatellite instability (MSI) analysis can be used to identify patients with a possible DNA mismatch repair defect [hereditary nonpolyposis colorectal carcinoma (HNPCC)]. The Bethesda criteria have been proposed to select families for determination of MSI. The aims
Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.
The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...
Shi, Zumin; Johnstone, Daniel; Talseth-Palmer, Bente A; Evans, Tiffany-Jane; Spigelman, Allan D; Groombridge, Claire; Milward, Elizabeth A; Olynyk, John K; Suchy, Janina; Kurzawski, Grzegorz; Lubinski, Jan; Scott, Rodney J
Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild-type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log-rank test p = 0.026, Wilcoxon p = 0.044, Tarone-Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power-prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC.
Yu, Li; Yin, Bo; Qu, Kaiying; Li, Jingjing; Jin, Qiao; Liu, Ling; Liu, Chunlan; Zhu, Yuxing; Wang, Qi; Peng, Xiaowei; Zhou, Jianda; Cao, Peiguo; Cao, Ke
In the present study, hereditary non-polyposis colorectal cancer (HNPCC) susceptibility genes were screened for using whole exome sequencing in 3 HNPCC patients from 1 family and using single nucleotide polymorphism (SNP) genotyping assays in 96 other colorectal cancer and control samples. Peripheral blood was obtained from 3 HNPCC patients from 1 family; the proband and the proband's brother and cousin. High-throughput sequencing was performed using whole exome capture technology. Sequences were aligned against the HAPMAP, dbSNP130 and 1,000 Genome Project databases. Reported common variations and synonymous mutations were filtered out. Non-synonymous single nucleotide variants in the 3 HNPCC patients were integrated and the candidate genes were identified. Finally, SNP genotyping was performed for the genes in 96 peripheral blood samples. In total, 60.4 Gb of data was retrieved from the 3 HNPCC patients using whole exome capture technology. Subsequently, according to certain screening criteria, 15 candidate genes were identified. Among the 96 samples that had been SNP genotyped, 92 were successfully genotyped for 15 gene loci, while genotyping for HTRA1 failed in 4 sporadic colorectal cancer patient samples. In 12 control subjects and 81 sporadic colorectal cancer patients, genotypes at 13 loci were wild-type, namely DDX20, ZFYVE26, PIK3R3, SLC26A8, ZEB2, TP53INP1, SLC11A1, LRBA, CEBPZ, ETAA1, SEMA3G, IFRD2 and FAT1 . The CEP290 genotype was mutant in 1 sporadic colorectal cancer patient and was wild-type in all other subjects. A total of 5 of the 12 control subjects and 30 of the 81 sporadic colorectal cancer patients had a mutant HTRA1 genotype. In all 3 HNPCC patients, the same mutant genotypes were identified at all 15 gene loci. Overall, 13 potential susceptibility genes for HNPCC were identified, namely DDX20, ZFYVE26, PIK3R3, SLC26A8, ZEB2, TP53INP1, SLC11A1, LRBA, CEBPZ, ETAA1, SEMA3G, IFRD2 and FAT1 .
Kallenberg, F G J; Aalfs, C M; The, F O; Wientjes, C A; Depla, A C; Mundt, M W; Bossuyt, P M M; Dekker, E
Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.
Meiser, B; Collins, V; Warren, R; Gaff, C; St John, D J B; Young, M-A; Harrop, K; Brown, J; Halliday, J
The psychological impact of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non-carriers) attending familial cancer clinics, using mailed self-administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post-notification of result (t = -3.98; p depression scores 2 weeks, 4 months and 12 months post-notification. Significant decreases from baseline for mean state anxiety scores were also observed for non-carriers 2 weeks post-notification (t = -3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non-carriers, and no adverse psychological outcomes were observed amongst carriers.
Campacci, N; de Lima, J O; Ramadan, L; Palmero, E I
Usually, the mass media do not address hereditary cancer and their risk factors, nor are these topics discussed at the community level. We used an informative guide on cancer and hereditary cancer, followed by a questionnaire on these topics to investigate the relevant knowledge among women at high risk for hereditary breast and/or colorectal cancer from a population-based cohort. The cohort was composed of 81 Brazilian women with positive family histories of breast and/or colorectal cancer. Strauss and Corbin's Grounded Theory was used for qualitative analysis. The average age of the cohort was 49.9 years old. Three participants (3.9%) were illiterate, 45 (59.2%) had attended elementary school, 14 (18.4%) had secondary school, and 14 (18.4%) held higher education degrees. A total of 47 (54.3%) volunteers were unable to fully understand the information provided in the guide because they did not know the meaning of words such as metastasis, malignant, hereditary, sporadic, or oncogenetics. Notwithstanding, the acceptance of the educational tool utilized was satisfactory, and it enhanced the volunteers' interest in a better understanding of cancer and heredity. Thereby, we concluded that the low knowledge of this important subject and the unawareness about fundamental terms required for the comprehension of this specific type of neoplasm made us believe that the use of the informative guide can provide a great value when used previously to the genetic counseling consultations. Besides, educational tools of easy understanding should be part of everyday clinical practice, from primary to specialized patient care.
Rau, T T; Dawson, H; Hartmann, A; Rüschoff, J
The pathologist can contribute to recognizing hereditary causes of colorectal cancer via morphology. By identifying so-called index patients, it is possible to take preventive measures in affected families. The precise definition of the clinical presentation and the histopathological phenotype help to narrow the spectrum of expected genetic alterations. Novelties within Lynch syndrome include the recognition of EPCAM as a fifth gene locus, as well as the newly defined Lynch-like syndrome with evidence of somatic mismatch repair (MMR) mutations. With regard to polyposis-associated syndromes, the spectrum of polyps, whether serrated, hamartomatous or classic adenoma, is of crucial importance. The resulting differential diagnosis includes (attenuated) familial adenomatous polyposis ([a]FAP), MUTYH-associated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), Peutz-Jeghers syndrome and juvenile polyposis, each with a specific genetic background.
Hasenbring, Monika I; Kreddig, Nina; Deges, Gabriele; Epplen, Joerg T; Kunstmann, Erdmute; Stemmler, Susanne; Schulmann, Karsten; Willert, Joerg; Schmiegel, Wolf
We prospectively examined the impact of an initial interdisciplinary genetic counseling (human geneticist, oncologist, and psycho-oncologist) on feelings of anxiety with a special focus on subgroups related to personal cancer history, gender, age, and education. At baseline, cancer-affected men revealed a significantly higher level of anxiety than unaffected men (pDepression Scale-A cases can be predicted by general distress (Brief Symptom Inventory) as well as by hereditary nonpolyposis colorectal cancer-related cognitions of intrusion and avoidance (impact of event scale) with a correct classification of 86%. Although initial hereditary nonpolyposis colorectal cancer counseling leads to an overall reduction of anxiety, differential effects of cancer history, gender, and age focus on subgroups of cancer-affected men, who may display unexpectedly high anxiety scores at baseline. Especially younger men do not seem to reduce this high anxiety level. Baseline anxiety was mainly determined by maladaptive situation-specific cognitions. Therefore, consulters should be more aware of anxiety-related cognitions in cancer-affected younger men.
Kessels, Koen; Eisinger, Joey D; Letteboer, Tom G; Offerhaus, G Johan A; Siersema, Peter D; Moons, Leon M G
To investigate whether sending a family history questionnaire to patients prior to undergoing colonoscopy results in an increased availability of family history and better genetic counseling. A questionnaire was mailed to patients before they underwent outpatient colonoscopy at a university hospital in 2013. These patients' additional characteristics and referral for genetic evaluation were retrieved from the electronic medical records. Patients undergoing inpatient coloboscopy, with confirmed hereditary colorectal cancer (CRC) or inflammatory bowel disease were excluded. All study patients from 2010 to 2013 were matched with the database of the genetics department to determine who consulted a geneticist. A total of 6163 patients underwent colonoscopy from 2010 to 2013. Of 1421 who underwent colonoscopy in 2013, 53 (3.7%) consulted a geneticist, while 75 (1.6%) of 4742 patients undergoing colonoscopy between 2010 and 2012 did so (P history was not recorded in the electronic medical records of 393 (40.3%). In 129 (32.8%), family history was obtained from the completed questionnaire. In 2013, 49 (60.5%) out of 81 patients referred for genetic counseling were referred based on their family history. Eight (9.9%) patients were referred based on the completed questionnaire. Screening for hereditary CRC in a population undergoing outpatient colonoscopy with a questionnaire sent by mail resulted in an increased availability of family histories and genetic counseling. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
Full Text Available HNPCC (Hereditary non-polyposis colorectal cancer development is caused by mutation of genes included in system of mismatch repair genes. The mutation exists at 60% of patients in hMSH2 gene, 30% in hMLH1 and 10% both in hPMS1and hPMS2 genes. RER+ exists in about 90% in hereditary non-polyposis colorectal cancer and about 15-28% in sporadic cancers.The purpose of the study was to determine highly sensitive microsatellite markers which can be fast and efficient way of microsatellite screening for detection of HNPCC patients. Moreover, we have analysed the loss of heterozygosity of tumour suppressor genes which could have the diagnostic value in detection of HPNCC patients.
Jonas, Susanna; Wild, Claudia; Schamberger, Chantal
The aim of this health technology assessment was to analyse the current scientific and genetic counselling on predictive genetic testing for hereditary breast and colorectal cancer. Predictive genetic testing will be available for several common diseases in the future and questions related to financial issues and quality standards will be raised. This report is based on a systematic/nonsystematic literature search in several databases (e.g. EmBase, Medline, Cochrane Library) and on a specific health technology assessment report (CCOHTA) and review (American Gastroenterological Ass.), respectively. Laboratory test methods, early detection methods and the benefit from prophylactic interventions were analysed and social consequences interpreted. Breast and colorectal cancer are counted among the most frequently cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gene is responsible for the increased cancer risk. In these families, high tumour frequency, young age at diagnosis and multiple primary tumours are remarkable. GENETIC DIAGNOSIS: Sequence analysis is the gold standard. Denaturing high performance liquid chromatography is a quick alternative method. The identification of the responsible gene defect in an affected family member is important. If the test result is positive there is an uncertainty whether the disease will develop or not, when and in which degree, which is founded in the geno-/phenotype correlation. The individual risk estimation is based upon empirical evidence. The test results affect the whole family. Currently, primary prevention is possible for familial adenomatous polyposis (celecoxib, prophylactic colectomy) and for hereditary mamma carcinoma (prophylactic mastectomy). The so-called preventive medical check-ups are early detection examinations. The evidence about early detection methods for colorectal cancer is better than for breast cancer. Prophylactic
Collins, Veronica R; Meiser, Bettina; Ukoumunne, Obioha C; Gaff, Clara; St John, D James; Halliday, Jane L
To fully assess predictive genetic testing programs, it is important to assess outcomes over periods of time longer than the 1-year follow-up reported in the literature. We conducted a 3-year study of individuals who received predictive genetic test results for previously identified familial mutations in Australian Familial Cancer Clinics. Questionnaires were sent before attendance at the familial cancer clinic and 2 weeks, 4 months, 1 year, and 3 years after receiving test results. Psychological measures were included each time, and preventive behaviors were assessed at baseline and 1 and 3 years. Psychological measures were adjusted for age, gender, and baseline score. The study included 19 carriers and 54 non-carriers. We previously reported an increase in mean cancer-specific distress in carriers at 2 weeks with a return to baseline levels by 12 months. This level was maintained until 3 years. Non-carriers showed sustained decreases after testing with a significantly lower level at 3 years compared with baseline (P depression and anxiety scores did not differ between carriers and non-carriers and, at 3 years, were similar to baseline. All carriers and 7% of non-carriers had had a colonoscopy by 3 years, and 69% of 13 female carriers had undergone gynecological screening in the previous 2 years. Prophylactic surgery was rare. This report of long-term data indicates appropriate screening and improved psychological measures for non-carriers with no evidence of undue psychological distress in carriers of hereditary nonpolyposis colorectal cancer mutations.
Ricker, Charité N; Hanna, Diana L; Peng, Cheng; Nguyen, Nathalie T; Stern, Mariana C; Schmit, Stephanie L; Idos, Greg E; Patel, Ravi; Tsai, Steven; Ramirez, Veronica; Lin, Sonia; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz-Josef; Figueiredo, Jane C
The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of
Mathers, John C; Movahedi, Mohammad; Macrae, Finlay
have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer. METHODS: In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo...
Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G
Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.
Chu Annie TW
Full Text Available Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. Results - Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 ± 9.2 years from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%, recovery (0% and 4.3%, delayed dysfunction (13% and 15.9% and resilience (76.8% and 66.7%. Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant
Ho, Samuel M Y; Ho, Judy W C; Bonanno, George A; Chu, Annie T W; Chan, Emily M S
Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 +/- 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression
Foster, L.; Jeon, P. [Health Sciences Center, Diagnostic Imaging, St. John' s, Newfoundland (Canada)]. E-mail: firstname.lastname@example.org; Green, J. [Health Sciences Center, Discipline of Genetics, Faculty of Medicine, St. John' s, Newfoundland (Canada)
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant trait characterized by presentation of colorectal cancer (CRC) at an early age and by an increased risk of other primary malignancies, including those of the endometrium. ovaries, stomach, small bowel, upper biliary tract, skin, and brain, as well as by transitional cell carcinoma (TCC) that especially involves the renal pelvis and ureter. Because specific genetic mutations causing HNPCC have been recently discovered, genetic screening options have been developed for some families. Subsequently, radiology has an increasing role in surveillance for and management of these HNPCC-associated tumours. Although colonoscopy is the mainstay of a screening regimen for colon cancer, the barium enema has been a standard radiologic investigation. Further, computed tomography (CT) colonography (now practised in various centres) will, with further refinement, prove to be of increasing value. Ultrasonography is a standard investigation for endometrial and ovarian cancer, with CT and magnetic resonance (MR) imaging often playing a central role. As for TCC, intravenous urography (IVU) had been a standard investigation tool. However, with continued evolution of multidetector row CT with postprocessing manipulation (CT urography [CTU]), the role of IVU is diminishing in most centres. Newfoundland has a high prevalence of HNPCC exhibiting a broad range of manifestations. In this article, radiologic images of various tumours from individuals with HNPCC demonstrate a radiologic spectrum of this fascinating hereditary disease. Screening implications and specific screening methods are reviewed. (author)
Ekstrand, Anna Isinger; JÃ¶nsson, Mats; Lindblom, Annika
The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT...... and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59...... and 75% and were strongly associated (P = 0.005). Reduced/lost PTEN expression was found in 63% of the tumors. Though HNPCC-associated colorectal cancers show simple genetic profiles with few chromosomal alterations, we demonstrate frequent and repeated targeting of the PI3K/AKT/mTOR pathway, which...
Lindberg, Lars Joachim; Ladelund, Steen; Frederiksen, Birgitte Lidegaard
BACKGROUND: Individuals with hereditary non-polyposis colorectal cancer (HNPCC) have a high risk of colorectal cancer (CRC). The benefits of colonic surveillance in Lynch syndrome and Amsterdam-positive (familial CRC type X familial colorectal cancer type X (FCCTX)) families are clear; only...... in the Lynch subgroup (2.0%) than in any other subgroup (0.0-0.4%, pLynch (3.6%) and non-Lynch (2.3-3.9%, p=0.28) subgroups. Non-Lynch Amsterdam-positive and Amsterdam-negative families were similar in their CRC (0.1-0.4%, p=0.......072), advanced adenoma (2.3-3.3%, p=0.32) and simple adenoma (8.4-9.9%, p=0.43) incidence. In moderate-risk families, no CRC and only one advanced adenoma was found. CONCLUSIONS: The risk of CRC in Lynch families is considerable, despite biannual surveillance. We suggest less frequent and more individualised...
Zhu, Viola W; Hinduja, Sanjay; Knezevich, Stevan R; Silveira, William R; DeLozier, Celia D
Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by a significant risk of colorectal and endometrial cancers. A variety of other epithelial cancers may be associated with this syndrome. Brian tumors are infrequent, but have been reported in series. Here, we report a case of a 34-year-old Caucasian woman with WHO grade III choroid plexus carcinoma (CPC). Comprehensive genomic profiling of the patient's resected brain tumor revealed mutations in six genes: PTEN, VHL, MSH6, NOTCH1, RB1, and TP53. Family history is significant for endometrial cancer in her mother and sister as well as colon cancer in her maternal grandfather suggestive of Lynch syndrome. Site-specific mutational analysis showed the MSH6 mutation (p.R482*) in peripheral lymphocytes. Subsequently we performed immunohistochemical staining of the tumor tissue which demonstrated widespread loss of MSH6 with intact MSH2, MLH1, and PMS2. The diagnosis of Lynch syndrome due to a mutation in MSH6 was therefore established. Our patient elected to have adjuvant radiation to the surgical bed only followed by prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy and is doing very well. To our knowledge, this is the first case report of CPC in an adult patient with a germline MSH6 mutation. We believe our data have provided molecular evidence to suggest that CPC could potentially be part of the Lynch syndrome spectrum. Published by Elsevier B.V.
Ripa, R S; Katballe, N; Wikman, F P
The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions......, identified after mutation screening of MSH2 and MLH1. All patients in the families were haplotyped using markers flanking the MSH2 gene. The haplotypes revealed that the five families with high probability descended from only two founders. The N596del segregated with the HNPCC phenotype with lod scores of 3.......2 and 2.0 at the recombination fraction of 0.0 in the two founder families. Sequencing of MSH2 and MLH1 did not reveal other pathogenic mutations, and N596del was not identified in 50 healthy controls. The mutation has previously been found expressed in mRNA, and is located in a conserved domain...
Ross, Emily; Broer, Tineke; Kerr, Anne; Cunningham-Burley, Sarah
Sociological literature has explored how shifts in the point at which individuals may be designated as diseased impact upon experiences of ill health. Research has shown that experiences of being genetically "at risk" are shaped by and shape familial relations, coping strategies, and new forms of biosociality. Less is known about how living with genetic risk is negotiated in the everyday and over time, and the wider forms of identity, communities and care this involves. This article explores these arrangements drawing on online bloggers' accounts of Familial Adenomatous Polyposis (FAP). We show how accounts of genetic risk co-exist with more palpable experiences of FAP in everyday life, notably the consequences of prophylactic surgeries. We consider how the act of blogging represents but also constitutes everyday experiences of hereditary cancer syndrome as simultaneously ordinary and exceptional, and reflect on the implications of our analysis for understanding experiences of genetic cancer risk.
Ghorbanoghli, Zeinab; Jabari, Carol; Sweidan, Walid; Hammoudeh, Wail; Cortas, George; Sharara, Ala I; Abedrabbo, Amal; Hourani, Ijad; Mahjoubi, Bahareh; Majidzadeh, Keivan; Tözün, Nurdan; Ziada-Bouchaar, Hadia; Hamoudi, Waseem; Diab, Osama; Khorshid, Hamid Reza Khorram; Lynch, Henry; Vasen, Hans
Colorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (Middle East was discussed and the idea was conceived to establish a network on hereditary colorectal cancer (HCCN-ME) with the goal of improving care for high-risk groups in the Middle East and (Eastern) Mediterranean Countries.
Vasen, H F A; Möslein, G; Alonso, A
of individuals at high risk for CRC prevents the development of advanced CRC. About 1 million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires...... recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum...... for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC...
Imyanitov Evgeny N
Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.
Jensen, Uffe Birk; Sunde, Lone; Timshel, Susanne
of MLH1, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33-66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though...
Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge
, clinical and MMR gene mutation data were retrieved. RESULTS: In a total of 105 cases of endometrial cancer, there was no significant difference in MSH2, MSH6 and MLH1 mutation carrier frequency. Compared to the general population, mutation carriers had a 20 times increase in lifetime risk of endometrial...
... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...
Pan, Min; Cong, Peikuan; Wang, Yue; Lin, Changsong; Yuan, Ying; Dong, Jian; Banerjee, Santasree; Zhang, Tao; Chen, Yanling; Zhang, Ting; Chen, Mingqing; Hu, Peter; Zheng, Shu; Zhang, Jin; Qi, Ming
The Human Variome Project (HVP) is an international consortium of clinicians, geneticists, and researchers from over 30 countries, aiming to facilitate the establishment and maintenance of standards, systems, and infrastructure for the worldwide collection and sharing of all genetic variations effecting human disease. The HVP-China Node will build new and supplement existing databases of genetic diseases. As the first effort, we have created a novel variant database of BRCA1 and BRCA2, mismatch repair genes (MMR), and APC genes for breast cancer, Lynch syndrome, and familial adenomatous polyposis (FAP), respectively, in the Chinese population using the Leiden Open Variation Database (LOVD) format. We searched PubMed and some Chinese search engines to collect all the variants of these genes in the Chinese population that have already been detected and reported. There are some differences in the gene variants between the Chinese population and that of other ethnicities. The database is available online at http://www.genomed.org/LOVD/. Our database will appear to users who survey other LOVD databases (e.g., by Google search, or by NCBI GeneTests search). Remote submissions are accepted, and the information is updated monthly. © 2011 Wiley Periodicals, Inc.
Frequency of hereditary colorectal cancer in Uruguayans patients with non polipotic colorectal cancer; Frecuencia de cancer colorrectal hereditario no polipotico en pacientes uruguayos con cancer colorrectal
Sarroca, C.; Della Valle, A.; Fresco, R.; Peltomaki, P.; Lynch, H. [Hospital Central de las Fuerzas Armadas, Montevideo (Uruguay)
Full text: Colonic Cancer Family Polipótic not (CCFNP) is a syndrome transmission autosomal dominant characterized by the aggregation of colorectal cancer (CCR), frequently associated with other solid tumors. Few studies have investigated CCFNP frequency in colorectal cancer patients. these have shown marked geographic variation (0.3% to 13%). The objective of this study is to estimate the frequency of a population CCFNP CCR carriers Uruguayan cancer patients. All patients consecutively operated CRC were included in the Hospital Central Armed Forces (Montevideo, Uruguay) between 1987 and 2003. The cases were classified into 3 groups: 1) those who met the criteria Amsterdam (CCFNP), 2) those who did not meet these criteria but considered as a population of increased risk of cancer based on family history / staff (PRI), and 3) sporadic CRC. Genetic analysis was performed for Detection of mutations in hMLH1, hMSH2 and hMSH6 gene in patients subgroup 1. 461 patients were included, with a median age of 66 years. The subgroup 1 represented 2.5% 2 5.6% and 91.8% sporadic CRC. 75% of cases CCFNP were classified as under 55. Mutations in hMLH1 / hMSH2/hMSH6 were found in 16.6% of cases included in the subgroup 1 (2 in hMLH1, 1 in hMSH2, hMSH6 none). The proportion of patients who met the Amsterdam criteria matches with that observed by other authors. However, the percentage of cases classified CCFNP identified as carriers of mutations is lower than that reported (16.6% vs. ~ 70%). This may reflect a different genetic profile Uruguayan population.
Shiloh, S; Koehly, L; Jenkins, J; Martin, J; Hadley, D
The emotional effects of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) provided within a counseling program were assessed among 253 individuals. Assessments were scheduled at baseline before testing, and again after 6 and 12 months post-test. Negative emotional reactions were evaluated using the Revised Impact of Event Scale and the Center for Epidemiological Studies-Depression Scale. Monitoring coping style was assessed at baseline using the Miller Behavioral Style Scale. Mean reductions were indicated in distress and depression levels within the first 6 months after counseling and testing. High monitors were generally more distressed than low monitors, specifically if they had indeterminate or positive results. Genetic counseling and testing for HNPCC do not result in long-term distress for most people. Of the variables investigated, only time and coping style have main effects on emotional reactions, and the impacts of mutation status are moderated by coping style. Psychological interventions, aimed to alleviate adverse emotional effects, were suggested for certain participants, i.e. recipients of positive or indeterminate results who are high monitors.
... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...
... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...
Bülow, Steffen; Kronborg, O
Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....
Okkels, Henrik; Larsen, K.L.; Thorlacius-Ussing, O.
INTRODUCTION:: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 2% to 4% of all colorectal cancer cases worldwide. Families with germ line mutations in 1 of 6 mismatch repair genes are known as Lynch syndrome families. The largest number...... this approach in Lynch families carrying mutations in MSH6. MATERIALS AND METHODS:: Results of the screening of the MSH6 gene in HNPCC families were compared with those obtained on immunohistochemical protein analysis. RESULTS:: In 56 (7%) of 815 families, at least 1 MSH6 mutation, 23 definitively pathogenic...... be detected, whereas in 34.5% pMSH6 was present and pMLH1/pPMS2 was absent. CONCLUSIONS:: If genetic screening of HNPCC families depended on immunohistochemical results, a substantial number of families harboring a pathogenic mutation in MSH6 and the vast majority of families harboring an MSH6 unclassified...
Montazer Haghighi, Mahdi; Radpour, Ramin; Aghajani, Katayoun; Zali, Narges; Molaei, Mahsa; Zali, Mohammad Reza
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found. The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing. We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient. In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutations.
Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie
Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...
Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola
the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated...
Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina
Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention....
... possible. Research will help us better understand whether chemotherapy can benefit elderly colorectal cancer patients. Such patients often do not receive chemotherapy due to concerns about side effects. We will ...
Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas
Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....
Bülow, Steffen; Kronborg, O
Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing with a w......Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....
Domanska, Katarina; Malander, Susanne; Staaf, Johan
(HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....
Burn, John; Gerdes, Anne-Marie; Macrae, Finlay
Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of as...
Katballe, Niels; Juul, Svend; Christensen, M.
was rejected in three of 14 cases (false-positive rate 21 per cent). Furthermore, seven of 18 probands whose families met the Amsterdam criteria I or II after verification were identified by further exploration in families who, according to the probands, met weaker criteria (false-negative rate 39 per cent......). CONCLUSION: The present study suggests that family studies on HNPCC are not reliable unless the diagnoses of family members are verified from official sources. If endoscopic screening is offered entirely on the basis of unverified information from patients with colorectal cancer, there is a risk that a large...
Olsen, Kim R.; Bojesen, Stig E.; Gerdes, Anne-Marie M.
for the group at high risk. The aim of the present study is to determine cost-effectiveness of surveillance programs where families at both high and moderate risk of HNPCC participate. METHODS: A decision analytic model (Markov model) is developed to assess surveillance programs where families at high......OBJECTIVES: Surveillance programs are recommended to both families at high risk (Amsterdam-positive families with known- and unknown mutation) and moderate risk (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost-effectiveness has so far only been estimated...
Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)
This paper describes colorectal cancer risk in relation to A-bomb radiation. The RERF Life Span Study has revealed the incidence of colorectal cancer to be significantly high in the group of A-bomb survivors than the control group. With regard to relative risk or excess relative risk, there is no definitive difference among sites in the colon. Risk for colon cancer is found to be linearly increased with increasing radiation doses, and in younger A-bomb survivors at the time of exposure. Risk associated with one Gy is estimated to be increased by double. There is no definitive variation between sex and between Hiroshima and Nagasaki. Excess relative risk would be increased rapidly with aging in the whole group of A-bomb survivors and with the cancer-prone age in younger A-bomb survivors at the time of exposure. (N.K.)
Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.
... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...
Wood, N J; Munot, S; Sheridan, E; Duffy, S R
Screening programs can reduce the burden of disease, however, they can be associated with raised levels of anxiety. The risk of endometrial and ovarian cancer is increased in hereditary nonpolyposis colorectal cancer (HNPCC). There is no prospective evidence to support screening for gynecological disease in HNPCC, however, current recommendations include the use of ultrasound and endometrial biopsy. This study assesses the impact of screening for gynecological cancer on self-reported symptoms of anxiety, depression, and perceptions of health. Women from HNPCC families attending gynecological screening (n = 26) completed the Hospital Anxiety and Depression Scale and the ShortForm36v2 questionnaires prior to screening with transvaginal ultrasound, outpatient/office hysteroscopy, endometrial biopsy, and ovarian tumor marker assessment (CA125). The same questionnaires were completed at 3 and 6 months following screening (15/26). Women in HNPCC families attending for gynecological screening did not have excess symptoms of anxiety or depression at baseline in subjective comparison to other populations. The process of screening and false positive screening results had no significant impact on symptoms of anxiety and depression or perceptions of health. We conclude that within the limitations of analysis in this small study group, screening for gynecological disease in HNPCC does not appear to be associated with any psychological morbidity.
van der Groep, P.
Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may
Yu, Hong; Li, Hui; Cui, Yongan; Xiao, Wei; Dai, Guihong; Huang, Junxing; Wang, Chaofu
Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by functional defects in mismatch repair (MMR) genes, including mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2). This study aimed to assess whether the mRNA expression of MLH1 in peripheral blood could be used as a biomarkers for the diagnosis of HNPCC. The mRNA level of MLH1 was determined in 19 HNPCC families (46 members) using real-time quantitative polymerase chain reaction (qPCR). The mRNA levels of MLH1 in HNPCC were significantly lower than controls (P MLH1 for the diagnosis of HNPCC with the area under curve of 0.858. At an optimal cut-off value (0.511), the mRNA level of MLH1 had a sensitivity of 81.3% and a specificity of 86.7% for distinguishing HNPCC from controls. In conclusion, the mRNA expression of MLH1 in peripheral blood may serve as a biomarker for the diagnosis of HNPCC.
Angele Martin K
Full Text Available Abstract Background Pulmonary sclerosing hemangioma (SH is a rare tumor of the lung predominantly affecting Asian women in their fifth decade of life. SH is thought to evolve from primitive respiratory epithelium and mostly shows benign biological behavior; however, cases of lymph node metastases, local recurrence and multiple lesions have been described. Case Presentation We report the case of a 21-year-old Caucasian male with a history of locally advanced and metastatic rectal carcinoma (UICC IV; pT4, pN1, M1(hep that was eventually identified as having hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome. After neoadjuvant chemotherapy followed by low anterior resection, adjuvant chemotherapy and metachronous partial hepatectomy, he was admitted for treatment of newly diagnosed bilateral pulmonary metastases. Thoracic computed tomography showed a homogenous, sharply marked nodule in the left lower lobe. We decided in favor of atypical resection followed by systematic lymphadenectomy. Histopathological analysis revealed the diagnosis of SH. Conclusions Cases have been published with familial adenomatous polyposis (FAP and simultaneous SH. FAP, Gardner syndrome and Li-Fraumeni syndrome, however, had been ruled out in the present case. To the best of our knowledge, this is the first report describing SH associated with Lynch syndrome.
... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...
He, J X; Jiang, Y F
Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.
... Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview What to Expect ... section Overview 2 of 6 sections The Basics: Colorectal Cancer What is colorectal cancer? Colorectal cancer is a ...
Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard
Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....
Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique
Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.
Hereditary colorectal cancer syndromes include Lynch syndrome and several polyposis syndromes (familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, and serrated polyposis syndrome). Learn about the genetics, clinical manifestations, management, and psychosocial aspects of these and other hereditary colon cancer syndromes in this expert-reviewed summary.
... for BRCA2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic ... and PALB2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic ...
Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra
The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.
Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David
Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
van der Post, Rachel S; Vogelaar, Ingrid P; Carneiro, Fátima
Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects......, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3...... the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic...
Lao, Victoria Valinluck; Grady, William M.
Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203
Zambirinis, Constantinos Pantelis; Theodoropoulos, George; Gazouli, Maria
Colorectal cancer (CRC), one of the most common cancers of the world, is actually a spectrum of several subtypes, with different molecular profiles, clinico-pathological characteristics and possibly separate pathways of progression. It is estimated that in approximately 25%-35% of cases, a familial component exists, so they are classified as familial CRC (fCRC). However the known hereditary CRC syndromes justify only up to 5%. The rest are attributed to some inherited genetic predisposition passed to offspring through low-penetrance genes, which in the proper environmental setting can bring on tumorigenesis. Furthermore, part of the familial clustering may be attributed to chance. Because of the complexity regarding the etiology of CRC, the clinician is sometimes faced with obscure patient data, and cannot be sure if they are dealing with fCRC or sporadic CRC. The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis, classification and treatment of CRC, but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.
... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...
Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.
Na, Soo-Young; Myung, Seung-Jae
Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.
Sidana, Abhinav; Srinivasan, Ramaprasad
The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.
Stol, Y.; Menko, F.H.; Westerman, M.J.; Janssens, M.J.P.A.
If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic
Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.
Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....
Jørgensen, Torben; Rafaelsen, Søren Rafael
The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship........59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...
Data have been accumulating to support an increased role for combined radiation therapy and surgery in the initial treatment of many rectal and some colonic carcinomas. These include the following findings: 1. Improvements in surgical survival rates have been minimal in the past 25 to 30 years and are the result of an increase in operability with little change by stage of disease in those patients who have survived a ''curative resection.'' 2. The incidence of local recurrence after potentially curative surgery is high in more advanced stages of disease for both rectal and colon cancer. Although palliation of local recurrence can frequently be obtained, its duration is often limited and the curative potential is low. Therefore, prevention of local recurrence with adjuvant radiation with or without chemotherapy is imperative. 3. When patients present with fixed, unresectable tumors, aggressive treatment combinations appear to improve both local control and survival. Close interaction is required between the surgeon and the radiation oncologist to achieve these results with an acceptable risk of complications
Plumb, A. A.; Halligan, S.
Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can...
He, Jin; Efron, Jonathan E
March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.
Middeldorp, Janneke Willemijn
Colorectal cancer (CRC) is one of the most common cancers in the Western world and in about 30% hereditary factors play a role. Although several genetic factors that predispose families to CRC are known, in many families affected with CRC the underlying genetics remain elusive. The work described in
Giglia, Matthew D; Chu, Daniel I
While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for < 5% of all CRCs, have identifiable germline mutations and phenotypes, such as Lynch syndrome and familial adenomatous polyposis (FAP). Familial CRCs, which account for up to 30% of CRCs, have no identifiable germline mutation or specific pattern of inheritance, but higher-than-expected incidence within a family. Since the discovery that certain genotypes can lead to development of CRC, thousands of mutations have now been implicated in CRC. These new findings have enhanced our ability to identify at-risk patients, initiate better surveillance, and take preventative measures. Given the large number of genes now associated with hereditary and familial CRCs, clinicians should be familiar with the alphabet soup of genes to provide the highest quality of care for patients and families.
McLoughlin, Monica Ramona
Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...
Frank Ulrich Weiss
Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.
A Comparison Between Denaturing Gradient Gel Electrophoresis and Denaturing High Performance Liquid Chromatography in Detecting Mutations in Genes Associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC and the Identification of 9 New Mutations Previously Unidentified by DGGE
Meldrum Cliff J
Full Text Available Abstract Denaturing high performance liquid chromatography is a relatively new method by which heteroduplex structures formed during the PCR amplification of heterozygote samples can be rapidly identified. The use of this technology for mutation detection in hereditary non-polyposis colorectal cancer (HNPCC has the potential to appreciably shorten the time it takes to analyze genes associated with this disorder. Prior to acceptance of this method for screening genes associated with HNPCC, assessment of the reliability of this method should be performed. In this report we have compared mutation and polymorphism detection by denaturing gradient gel electrophoresis (DGGE with denaturing high performance liquid chromatography (DHPLC in a set of 130 families. All mutations/polymorphisms representing base substitutions, deletions, insertions and a 23 base pair inversion were detected by DHPLC whereas DGGE failed to identify four single base substitutions and a single base pair deletion. In addition, we show that DHPLC has been used for the identification of 5 different mutations in exon 7 of hMSH2 that could not be detected by DGGE. From this study we conclude that DHPLC is a more effective and rapid alternative to the detection of mutations in hMSH2 and hMLH1 with the same or better accuracy than DGGE. Furthermore, this technique offers opportunities for automation, which have not been realised for the majority of other methods of gene analysis.
... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English (US) ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...
Christensen, Mariann; Katballe, Niels; Wikman, Friedrik
BACKGROUND: Germline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high...... carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty-five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced. RESULTS: Ninety-two percent of patients...... the three methods was found in 74 % of the tumors. CONCLUSIONS: The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated....
Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.
This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131 I at a total dose of at least 1.0 μCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131 I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131 I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures
Cox, Thomas R; Erler, Janine T
Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... advancements in the field of colorectal cancer....
Quintero, Enrique; Saito, Yutaka; Hassan, Cessare; Senore, Carlo
Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should wo...
Full Text Available Colorectal cancer (CRC is the third most common cause of cancer death in the world. The incidence rate (ASR and age distribution of this disease differ between most of African-Middle-Eastern (AMAGE and North America and Europe for many reasons. However, in all areas, “CRC” is considered as one of the most preventable cancers, because it might develop from variant processes like polyps and IBD in addition to the genetic pathogenesis which became very well known in this disease. We tried in this paper to review all the possible reasons of the differences in incidence and age between the west and AMAGE. Also we reviewed all the mutations that lead to the hereditary and familiar clustering of this disease with the correlations with the surrounding food and environment of different areas. Then, we focused on the precancerous pathology of this disease with special focusing on early detection depending on new endoscopy technology and most important genetic studies. We lastly reviewed the evidence of some of the surveillance and put suggestions about future surveillance programs and how important those programs are on the psychological aspect of the patients and their families.
Surgical management of hereditary colorectal cancer: surgery based on molecular analysis and family history Manejo quirúrgico del cáncer colorrectal hereditario: cirugía basadas en el análisis molecular y los antecedentes familiares
Full Text Available The importance of colorectal cancer (CRC is increasing. A proportion show a hereditary component, as in Lynch syndrome and Familial Adenomatous Polyposis, and a recently defined entity as well, namely, Familial Colorectal Cancer type X. The high probability to develop CRC in these groups may, at the time of recognition, change surgical management, including its timing or even the surgical technique. In some cases prophylactic surgery can play an important role. The possibility of using tools that allow recognition of the aforementioned syndromes, including microsatellite instability, immunohistochemistry for DNA mismatch repair system proteins, and especially their mutations, is on the basis of therapeutic strategies that differ from those employed in sporadic CRC cases.
Full Text Available Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.
Weiss, Frank U.
Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...
Cascorbi, Ingolf; Werk, Anneke Nina
Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Moreover, the association between genetic variants of drug transporters with the clinical outcome is comprehensively discussed. Expert opinion: Precision therapy in the field of oncology is developing tremendously. There are a number of somatic tumor genetic markers that are indicative for treatment with anti-cancer drugs. By contrast, for some hereditary variants, recommendations have been developed. Although we have vast knowledge on the association between drug transporter variants and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. Further developments in research may lead to the discovery of rare, but functionally relevant single nucleotide polymorphisms and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.
Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.
Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen
There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.
Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard
We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.
Full Text Available El cáncer colorrectal hereditario no poliposo (CCHNP se relaciona con mutaciones en los genes reparadores de ADN (MLH1, MSH2 y MSH6. La mayoría de estas alteraciones son familia-específicas y su detección suele requerir la secuenciación completa de los genes relacionados. Se detectó una mutación puntual (2269-2270insT en el último codón del gen MLH1 en familias de un área del norte de Italia (Reggio Emilia y su origen se considera debido a un efecto fundador. En este trabajo presentamos una familia mendocina con CCHNP portadora de la misma mutación, cuyos ancestros eran oriundos de Reggio Emilia. Para la detección de la mutación se diseñó una estrategia basada en PCR y posterior corte enzimático. La mutación fue hallada en tres integrantes de la familia estudiada, dos de los cuales no presentaban sintomatología clínica. Estos pacientes fueron seguidos preventivamente mediante colonoscopias. La metodología utilizada en nuestro laboratorio fue específica y sensible para la detección de una mutación previamente registrada y permitió realizar el diagnóstico genético molecular en el país, evitando el envío de muestras al extranjero. Es de importancia destacar que el diagnóstico genético pre-sintomático de cáncer hereditario, enfocado desde un grupo multidisciplinario de profesionales, permite un mejor seguimiento y apoyo a las familias afectadas.Hereditary non polyposis colorectal cancer (HNPCC has been related to mutations in the DNA mismatch repair genes (MLH1, MSH2 y MSH6. Mutation detection analysis requires the complete sequencing of these genes, given the high frequency of family-specific alterations. A point mutation (2269- 2270insT in the last codon of the MLH1 gene has been detected in families from a northern region of Italy (Reggio Emilia.Given that this alteration was registered only in people from this region, it has been considered a founder mutation. In this work, we present an Argentine HNPCC family
Moreno, Courtney; Kim, David H; Bartel, Twyla B; Cash, Brooks D; Chang, Kevin J; Feig, Barry W; Fowler, Kathryn J; Garcia, Evelyn M; Kambadakone, Avinash R; Lambert, Drew L; Levy, Angela D; Marin, Daniele; Peterson, Christine M; Scheirey, Christopher D; Smith, Martin P; Weinstein, Stefanie; Carucci, Laura R
This review summarizes the relevant literature regarding colorectal screening with imaging. For individuals at average or moderate risk for colorectal cancer, CT colonography is usually appropriate for colorectal cancer screening. After positive results on a fecal occult blood test or immunohistochemical test, CT colonography is usually appropriate for colorectal cancer detection. For individuals at high risk for colorectal cancer (eg, hereditary nonpolyposis colorectal cancer, ulcerative colitis, or Crohn colitis), optical colonoscopy is preferred because of its ability to obtain biopsies to detect dysplasia. After incomplete colonoscopy, CT colonography is usually appropriate for colorectal cancer screening for individuals at average, moderate, or high risk. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.
Li-song TENG; Yi ZHENG; Hao-hao WANG
Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.
Background. In families with hereditary cancer, at-risk individuals can benefit from genetic counselling and testing. General practitioners (GPs) are ideally placed to identify such families and refer them appropriately. Objective. To assess the practices, knowledge and attitudes of GPs regarding common hereditary cancers.
Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Gómez García, Encarna; Ruijs, Mariëlle; Verhoef, Senno
The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.
Quirke, P; Morris, E
The management of colorectal cancer is a team process. High-quality reporting of colorectal cancer is very important as the whole team relies upon the skill of the pathologist. Failure to report key features can lead to undertreatment of this disease. The use of a proforma has been demonstrated to be beneficial and we recommend staying with TNM5 due to scientific and reproducibility issues with TNM6. Important features in stage II/Dukes' B cases are extramural vascular invasion, peritoneal involvement, extent of extramural spread, incomplete resection and perforation. All of these may lead to adjuvant therapy being administered. The surgically created circumferential resection margin (CRM) and the mode of its creation are important features and the CRM retains its value after preoperative therapy. Regression grading should be applied only to fully resected tumours and the dissection and sampling must be standardized to allow comparison of results between trials and centres. When reporting local resections of early-stage cancers we need to look for features that predict spread to local lymph nodes to allow a full resection to be considered.
Cognitive Impairment; Stage 0 Colorectal Cancer; Stage I Colorectal Cancer; Stage II Colorectal Cancer; Stage IIA Colorectal Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage III Colorectal Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer
Porteous, M; Dunckley, M; Appleton, S; Catt, S; Dunlop, M; Campbell, H; Cull, A
In this pilot study, the acceptability of approaching 111 newly diagnosed colorectal cancer patients with the offer of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) was assessed. A total of 78% of participants found it highly acceptable to have the information about HNPCC brought to their attention at that time.
Petersen, Sanne M; Dandanell, Mette; Rasmussen, Lene J
Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomi...
Landsbergen, K.M.; Prins, J.B.; Brunner, H.G.; Duijvendijk, P. van; Nagengast, F.M.; Krieken, J.H.J.M. van; Ligtenberg, M.J.; Hoogerbrugge-van der Linden, N.
According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second
Chan, Andrew T; Giovannucci, Edward L
Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence.
Myrhøj, T; Andersen, M-B; Bernstein, I
AIM: The aim of this study was to evaluate if Urine Cytology (UC) is an appropriate screening procedure for detecting urinary tract neoplasia at an early stage in persons at risk in Hereditary Non-Polyposis Colorectal Cancer families. METHOD: In the National Danish HNPCC-register persons at risk ...
Kruhøffer, M; Jensen, J L; Laiho, P
The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI...... of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated...... is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression...
Valentina S. Vysotskaia
Full Text Available The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs, short insertions and deletions (indels, and copy number variants (CNVs in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA. We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.
Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N
Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.
Full Text Available After lung cancer colorectal cancer (Cc is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(µm thick were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16% with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.
Roberta Vasconcelos e Silva
Full Text Available Hereditary nonpolyposis colorectal cancer is an autosomal dominant condition caused by highly penetrant gene mutations. It is characterized by increased susceptibility for a specific group of cancer, mainly colorectal cancer. The syndrome originates from the inheritance of mutations in DNA mismatch repair genes. The most commonly affected genes in hereditary nonpolyposis colorectal cancer are hMLH1 and hMSH2. Their deficient expression renders the cell susceptible to the accumulation of many molecular defects, a condition which can be evaluated by the instability in sections of base repeats in the genoma known as microsatellite instability. The molecular detection of hereditary nonpolyposis colorectal cancer is possible in most of the highly suspicious cases. Genetic tests for hereditary nonpolyposis colorectal cancer also allow characterization of the individual that bears the mutation within a family. The high cost and restricted availability of these tests hamper their use for every person presenting colorectal cancer. Due to this fact, some clinical criteria have been developed by a hereditary nonpolyposis colorectal cancer international organization to select families with a high probability of carrying the mutation. Once families at risk are identified, they are encouraged to join a screening program that aims at early detection of hereditary nonpolyposis colorectal cancer-related cancers, increasing the possibility of its prevention and early detection.O câncer colo-retal hereditário não polipose é uma síndrome genética caracterizada por uma susceptilidade aumentada para certos tipos específicos de câncer, especialmente o câncer colo-retal. Ao nível molecular, a síndrome caracteriza-se pela herança autossômica dominante de mutações em genes envolvidos em um mecanismo de reparo do DNA dirigido para defeitos em trocas, ganhos ou perdas de um número de pequeno de bases, chamado de sistema de reparo de erros de pareamento. Os
Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H
AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long...
Hano Garcia, Olga Marina; Wood Rodriguez, Lisette; Villa Jimenez, Oscar Manuel
Obesity is a chronic and multifactor disease characterized by presence of excess body fat harmful for health. Several studies have been conducted to assess the possible risk character of different factors for colorectal cancer including the following modifying factors: a diet rich in saturated fats, a diet low in vegetables, physical inactivity, alcohol consumption and obesity. A case-control study was conducted to include 276 adult patients (93 cases and 184 controls) consecutively seen from May, 2008 to May, 2009 in the Institute of Gastroenterology determining a possible association between obesity as risk factor and colorectal cancer. Variables measures included: sex, age, skin color, body mass index, hip-waist circumference and endoscopic location of cancer. We conclude that the colorectal cancer with predominance in female sex and in white people in both groups. Obesity according to a great relation hip-waist had an strong relation with colorectal cancer, which had predominance towards distal colon in both sexes
Yu, Jiekai; Huang, Yanqin; Lin, Chen; Li, Xiaofen; Fang, Xuefeng; Zhong, Chenhan; Yuan, Ying; Zheng, Shu
The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85.0% accuracy. The model distinguishing CRA-H from healthy individuals was established with 90.0% specificity and 86.7% sensitivity. Additionally, five peaks (2202, 5821, 3260, 2480, and 2218) showing differential expression in advanced colorectal adenoma patients with a family history of colorectal cancer were selected. The protein Kininogen 1 (KNG1) was identified in colorectal adenoma patients and validated using Western Blotting. KNG1 may be a biomarker for colorectal adenoma patients with a family history of colorectal cancer. PMID:29535795
... Products For Consumers Home For Consumers Consumer Updates Colorectal Cancer: What You Should Know Share Tweet Linkedin Pin ... with—and more than 50,000 died from—colorectal cancer, according to the National Cancer Institute. It is ...
Murakami, Yoshie; Okamura, Hitoshi; Sugano, Kokichi; Yoshida, Teruhiko; Kazuma, Keiko; Akechi, Tatsuo; Uchitomi, Yosuke
To the authors' knowledge, there have been few studies of the psychologic distress after disclosure of genetic test results for hereditary nonpolyposis colorectal carcinoma (HNPCC). The objectives of this study were to identify the prevalence rates and predictors of psychologic distress and to evaluate the feelings of guilt after disclosure of the test results in Japanese probands and unaffected relatives. Probands and unaffected relatives were interviewed immediately after the first genetic counseling session for HNPCC and again 1 month after disclosure of the genetic test results. The prevalence of major and minor depression, acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and posttraumatic stress symptoms (PTSS) were assessed using the Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R) or the DSM-IV; feelings of guilt were investigated using a numeric scale and a semistructured interview. Among 47 participants who completed the baseline interview, 42 participants (89%) completed the 1-month follow-up interview. Although none of the participants met the criteria for major depression, ASD, or PTSD at the follow-up interview, 3 of 42 participants (7%) met the criteria for minor depression and 2 participants (5%) had PTSS. The only predictor of psychologic distress found was the presence of a history of major or minor depression (odds ratio, 19.41; 95% confidence interval, 1.42-264.95; P depression and PTSS. Copyright 2004 American Cancer Society.
Rafaelsen, Søren Rafael
SUMMARYBackground and purpose Colorectal cancer is a common disease in Denmark with considerable morbidity and mortality. Although survival in recent years has improved, Denmark still has the lowest 5-year survival compared to the other Nordic countries. The treatment of patients depends on local...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...... of 295 patients with primary colorectal cancer we found a sensitivity of preoperative ultrasound, surgical exploration, and intraoperative ultrasound of 70%, 84%, and 97%, respectively, based on a patient-by-patient comparison (p
B. Shafayan M. Keyhani
This study was carried out to analyze certain epidemiological variations in Iranian patients with colorectal cancer. (CRC): From March 1981 up to March 1993, 103 patients were analyzed retrospectively for age, gender, marital state, job, nutritional habits, presenting symptoms and histopathological features. Most of the patients with colorectal cancer were male, age range 20-75 (mean 56), 25.4 percent were long-term smokers and bleeding was the most common symptom. The rectum was the most com...
Freeman, H J
Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.
Hugh J Freeman
Full Text Available Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%. All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%, no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.
Kensuke Otani; Soichiro Ishihara; Keisuke Hata; Koji Murono; Kazuhito Sasaki; Koji Yasuda; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Kazushige Kawai; Hiroaki Nozawa; Hironori Yamaguchi; Toshiaki Watanabe
Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological ...
Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael
Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....
Albrethsen, Jakob; Knol, Jaco C; Piersma, Sander R
for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we......Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers...... with statistics, we identified proteins that are significantly enriched in the nuclear matrix fraction relative to two earlier fractions (the chromatin-binding and intermediate filament fractions) isolated from six colorectal tissue samples. The total data set contained 2,059 non-redundant proteins. Gene ontology...
I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)
textabstractColorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to
Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.
Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The
Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il
Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...
Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
An oncologist (cancer doctor) shares her medical and personal advice for people between the ages of 50 and 75 about getting screened for colorectal cancer. Created: 4/6/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP). Date Released: 4/6/2017.
Broek, Colette Bernadine Maria-Theresia van den
Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with
Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo
The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)
-, č. 3 (2011), s. 1421-1431 ISSN 1945-0524 R&D Projects: GA AV ČR IAA500200917 Institutional research plan: CEZ:AV0Z50200510 Keywords : colorectal cancer * inflammation * tumor Subject RIV: EC - Immunology
B. Shafayan M. Keyhani
Full Text Available This study was carried out to analyze certain epidemiological variations in Iranian patients with colorectal cancer. (CRC: From March 1981 up to March 1993, 103 patients were analyzed retrospectively for age, gender, marital state, job, nutritional habits, presenting symptoms and histopathological features. Most of the patients with colorectal cancer were male, age range 20-75 (mean 56, 25.4 percent were long-term smokers and bleeding was the most common symptom. The rectum was the most common site and moderately differentiated carcinoma was considered as the main common histopathological variety. In conclusion, increasing incidence of colorectal cancer in younger Iranian population, below 30 and late admission and diagnosis were the main findings in the present study necessitating screening programs with annual fecal occult blood tests in high risk families.
Skoglund, J; Djureinovic, T; Zhou, X-L
BACKGROUND: The best known hereditary colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), constitute about 2% of all colorectal cancers, and there are at least as many non-FAP, non-HNPCC cases where the family history suggests...... a dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2-31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. METHODS: Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had...... previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. RESULTS: In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32-31.1 with a multipoint LOD...
Ogino, Shuji; Goel, Ajay
Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...
A health economist talks about studies on figuring out the costs of running a colorectal cancer screening program, and how this can lead to better screening. Created: 4/4/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP). Date Released: 4/4/2017.
Larsen, Julie Mou; Christensen, Ib Jarle; Nielsen, Hans Jørgen
monoclonal syncytin antibody we have assessed syncytin expression in a retrospective series of 140 colorectal cancer patients. Variable degrees of syncytin expression were detected in both colonic and rectal tumors and the prognostic impact of such expression was analysed with the Kaplan-Meier method...... and the Cox proportional hazard model. Interestingly, increased syncytin expression was associated with decreased overall survival in rectal but not in colonic cancer patients. Thus, the prognostic impact of syncytin expression appears to vary with the tumor type....
Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie
Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...
Gu, Meng-Jia; Huang, Qiu-Chi; Bao, Cheng-Zhen; Li, Ying-Jun; Li, Xiao-Qin; Ye, Ding; Ye, Zhen-Hua; Chen, Kun; Wang, Jian-Bing
Background Colorectal cancer is the 4th common cancer in China. Most colorectal cancers are due to modifiable lifestyle factors, but few studies have provided a systematic evidence-based assessment of the burden of colorectal cancer incidence and mortality attributable to the known risk factors in China. Methods We estimated the population attributable faction (PAF) for each selected risk factor in China, based on the prevalence of exposure around 2000 and relative risks from cohort studies a...
Yao, Caroline; Nash, Guy F; Hickish, Tamas
Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and a...
P.G. van Putten (Paul)
textabstractColorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer in the Western world. Screening has been shown to reduce CRC incidence and mortality. The first evidence that colorectal cancer screening could effectively reduce mortality dates
Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P
The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.
Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder
Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...
Tan, D S P; Marchiò, C; Reis-Filho, J S
Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.
Full Text Available Neste trabalho relatamos o caso de um paciente portador de síndrome de Lynch (HNPCC que desenvolveu câncer retal metacrônico em curto intervalo de tempo após tratamento do tumor primário (câncer de cólon direito. O objetivo deste relato de caso é salientar a importância da suspeição clínica no diagnóstico de câncer colorretal hereditário e suas implicações terapêuticas.In this article we report the case of a patient with Lynch syndrome (HNPCC who developed metachronic rectal cancer in a short time interval after the primary tumor had been treated (right colon cancer. The objective of this case report is to point out the importance of clinical suspicion in the diagnosis of hereditary colorectal cancer and its therapeutics implications.
Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H
The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001-2003 to database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long
Carethers, John M; Stoffel, Elena M
Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352
Carethers, John M; Stoffel, Elena M
Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.
The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.
The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.
Full Text Available MAP (MUTYH-associated polyposis is a syndrome, described in 2002, which is associated with colorectal adenomas, with enhanced colorectal carcinogenesis. This review synthesizes the available literature on MAP and outlines its pathogenesis, association with colorectal tumorigenesis, screening, treatment, and the subtle differences between it and its close cousins—FAP and AFAP. The preponderance of data is collected using MAP guidelines. However, although AFAP and MAP appear similar, potentially important distinctions exist, warranting targeted diagnostic criteria and treatment approaches. We suggest that it may be prudent to screen for MAP earlier than in current clinical practice, as it has been shown that sequence variants are associated with more severe disease, presenting with an earlier onset of colorectal cancer. Finally, we issue a call-to-action for much-needed further data to establish clear clinical and diagnostic criteria.
Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.
Joana Pedro Lopes; Paula Manuela de Castro Cardoso Pereira; Ana Filipa dos Reis Baltazar Vicente; Alexandra Bernardo; María Fernanda de Mesquita
The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery...
Lee, Young Joong; Kang, Hee Tae; Kim, Jong Deok; Rhee, Hak Song
The incidence of colorectal cancer of Korea is much lower than that of Western countries, but has shown a tendency to a slight increase recently. Barium enema is the most valuable, noninvasive and inexpensive method available to evaluate the size, shape and site of colorectal cancer. The authors reviewed and radiologically classified barium enema studies of 232 cases of colorectal cancer from Aug. 1967 to July 1982 at Presbyterian Medical Center, Jeonju, Confirmed clinically, operatively and pathologically. The results were as follows; 1. The ratio of male and female was 1.3:1, and youngest was 13 year-old and the oldest 86 year-old. 2. The peak incidence occurred from 5th to 7th decades, accounting for 78% of all cases (181/232), and there was a relatively high incidence of the disease in patients below 30 years of age at 7.8% (18/232). 3. Rectum and rectosigmoid region are the most frequently involved regions (127/232:54.8%). 4. The positivity of barium enema examination was 4.0% (232/5807), and its accuracy was 96.5% (224/232). 5. The radiologic findings were classified into 4 groups, and they were annular encircling 62.9% (146/232). polypoid fungating 26.8% (62/232), infiltrating 8.6% (20/232), and primary ulcerating 1.7% (4/232) in order of frequency. 6. The linear length of the cancer ranged from 1.5 Cm to 15 Cm, and the average length was 5.5 Cm. 7. There was no statistical correlation between the length of lesion, the site, and the radiologic findings, and stages of the lesion (P:0.750-0.250). 8. The majority of colorectal cancers was adenocarcinoma (217/232:93.6%)
R.G.S. Meester (Reinier)
markdownabstractColorectal cancer is a leading cause of cancer deaths. Screening for colorectal cancer is implemented in an increasing number of settings, but performance of programs is often suboptimal. In this thesis, advanced modeling, informed by empirical data, was used to identify areas for
Tayyem, Reema F.; Bawadi, Hiba A.; Shehadah, Ihab; Agraib, Lana M.; AbuMweis, Suhad S.; Al-Jaberi, Tareq; Al-Nusairr, Majed; Bani-Hani, Kamal E.; Heath, Dennis D.
Summary Background & aimsDietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. MethodsDietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, g...
Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP
Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...
Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M; Jamieson, Saara H; Balachandran, Samanthy; Borowsky, Jennifer; Liu, John; Kawamata, Futoshi; Bond, Catherine E; Rosty, Christophe; Burge, Matthew E; Buchanan, Daniel D; Leggett, Barbara A; Whitehall, Vicki L J
The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers
Cancer Survivor; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8
Pedro J. Tárraga López
B6 is also associated with a higher risk of developing colon cancer with an overexpression of p53. Eating pulses at least three times a week lowers the risk of developing colon cancer by 33%, after eating less meat, while eating brown rice at least once a week cuts the risk of CRC by 40%. These associations suggest a dose–response effect. Frequently eating cooked green vegetables, nuts, dried fruit, pulses, and brown rice has been associated with a lower risk of colorectal polyps. High calcium intake offers a protector effect against distal colon and rectal tumors as compared with the proximal colon. Higher intake of dairy products and calcium reduces the risk of colon cancer. Taking an aspirin (ASA regularly after being diagnosed with colon cancer is associated with less risk of dying from this cancer, especially among people who have tumors with COX-2 overexpression. 16 Nonetheless, these data do not contradict the data obtained on a possible genetic predisposition, even in sporadic or non-hereditary CRC. CRC is susceptible to screening because it is a serious health problem given its high incidence and its associated high morbidity/mortality. Conclusions (1 Cancer is a worldwide problem. (2 A modification of diet and lifestyle could reduce morbidity and mortality. (3 Early detection through screening improves prognosis and reduces mortality.
Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.
Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, fo...
Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7
Matsukawa, M.; Usui, Y.; Kobayashi, S.
The incidence of colorectal cancer has been gradually increasing in Japan, and if the present rate of increase is maintained it has been estimated that it will become the most common of all malignant neoplasms by the year 2000. It has been proved that colorectal cancer can be completely cured, if it is treated in its early phase. Early cancer of the large bowel is defined as a cancer which is limited to the mucosal membrane or submucosal layer, regardless of lymph node and distant metastases. Detection of early cancer improves the overall curability of colorectal cancer. The greatest number of early cancers of the large bowel are polypoid lesions in their macroscopic form, and depressed lesions are rarely encountered. Accordingly, the first step in the detection of early cancer starts with the screening of polypoid lesion by radiology and endoscopy. This paper is concerned with diagnostic accuracy of radiology in the screening of colorectal cancer with endoscopic correlation
Nordholm-Carstensen, Andreas; Wille-Jørgensen, Peer A; Jorgensen, Lars N
This study aimed to estimate the prevalence of indeterminate pulmonary nodules and specific radiological and clinical characteristics that predict malignancy of these at initial staging chest computed tomography (CT) in patients with colorectal cancer. A considerable number of indeterminate...... pulmonary nodules, which cannot readily be classified as either benign or malignant, are detected at initial staging chest CT in colorectal cancer patients....
treatment and follow up were included. Patient ... and recurrence and the associated patient and disease ... The incidence of colorectal cancer (CRC) in the devel- ... therapy, disease stage and curative intent (table 3). ... through genetic and family analyses (4,6). ... Polite BN, Dignam JJ: A colorectal cancer model of health.
Harten-Gerritsen, van Suzanne; Balvers, Michiel G.J.; Witkamp, Renger F.; Kampman, Ellen; Duijnhoven, van F.J.B.
Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a
Palmero Edenir I
Full Text Available Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2 had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65. Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at
Brittain, Kelly; Pennings Kamp, Kendra J; Salaysay, Zachary
Colorectal cancer is the third leading cause of cancer death among U.S. women. Women report being screened for colorectal cancer less often than men, and if colorectal cancer screening guidelines were routinely followed, approximately 60% of colorectal cancer deaths could be prevented. Many colorectal cancer screening interventions have not used Facebook, which is the most popular social media site among women. Little is known about engaging women in colorectal cancer screening and risk reduction information using Facebook. The "Colorectal Cancer Screening Awareness for Women" Facebook page was created to promote colorectal cancer screening and risk reduction awareness among women. Facebook posts targeted women aged 45-64 years and highlighted colorectal cancer screening methods, guidelines, and colorectal cancer risk reduction strategies. Demographics and data about the women's interactions with the page were collected using Facebook analytics and analyzed. The majority of the 391 users of the Colorectal Cancer Screening Awareness for Women Facebook page were women aged 45-54 years (56.5%). The most "liked" posts were related to colorectal cancer risk reduction behaviors. In an effort to increase routine colorectal cancer screening and colorectal cancer risk reduction behaviors, gastroenterology nurses and practices should consider Facebook as a good method to regularly engage women in colorectal cancer screening and colorectal cancer risk reduction information.
Zanders, M. M. J.; Vissers, P. A. J.; Haak, H. R.; van de Poll-Franse, L.
Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes
Hochster, Howard S.
Colon cancer, though already metastatic, may still be curable through multi-modality approaches, which require combined planning between medical and surgical oncologists. Retrospective surgical series have historically shown 5-year survival or “cures” for 30% to 50% of patients with solitary or a few resectable liver metastases. The role of adjuvant chemotherapy in this setting has been poorly defined. A recent European Organization for Research and Treatment of Cancer (EORTC) study randomize...
This podcast is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer.
Tayyem, Reema F; Bawadi, Hiba A; Shehadah, Ihab; Agraib, Lana M; AbuMweis, Suhad S; Al-Jaberi, Tareq; Al-Nusairr, Majed; Bani-Hani, Kamal E; Heath, Dennis D
Dietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. Dietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, gender, occupation and marital status). The data was collected between January 2010 and December 2012, using interview-based questionnaires. Multivariate logistic regression was used to estimate the relationship between dietary choices and risk of developing colorectal cancer. Factor analysis revealed three major dietary patterns. The first pattern we identified as the "Healthy Pattern", the second was identified as "High Sugar/High Tea Pattern" and the third as "Western Pattern". In the Healthy Pattern group we found a 10.54% variation in food intake, while the intake variation was 11.64% in the Western Pattern. After adjusting for confounding factors, the Western Pattern food choice was found to be significantly associated with an increased risk of developing CRC (OR = 1.88; 95% CI = 1.12-3.16). The results for the Healthy and High-Sugar/High Tea Patterns showed a decrease, but the statistic was not significant for the risk of CRC development. The Western Pattern of dietary choice was directly associated with CRC. The association between the dietary food choice in the Healthy and High-Sugar/High Tea Patterns and colorectal cancer needs further study in our Jordanian population. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Wong, Ashley; Ma, Brigette B Y
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Several important scientific discoveries in the molecular biology of CRC have changed clinical practice in oncology. These included the comprehensive genome-wide profiling of CRC by the Cancer Genome Atlas Network, the discovery of mutations along the RAS-RAF signaling pathway as major determinants of response to antibodies against the epidermal growth factor receptor, the elucidation of new molecular subsets of CRC or gene signatures that may predict clinical outcome after adjuvant chemotherapy, and the innovative targeting of the family of vascular endothelial growth factor and receptors. These new data have allowed oncologists to individualize drug therapy on the basis of a patient's tumor's unique molecular profile, especially in the management of metastatic CRC. This review article will discuss the progress of personalized medicine in the contemporary management of CRC. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
Salama, Paul; Platell, Cameron
Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.
Yao, Caroline; Nash, Guy F; Hickish, Tamas
Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and addresses the issues that arise in diagnosing and treating this patient group. By highlighting these difficulties, this review aims to improve understanding and to provide clearer insight into both surgical and non-surgical management.
Garber, J E; Patenaude, A F
Genetic testing for hereditary susceptibility to disease is new. Much has been learned from experience with Huntington's disease and other non-malignant conditions. There are some differences in the case of predisposition testing for cancer: there is often the perception that cancer is preventable and sometimes curable, in contrast to other hereditary conditions. Testing raises many issues new to the medical community and to the public as well. There is great concern that the explosive technology be used responsibly, so that the potential benefits of genetic knowledge are not eclipsed by the risks to autonomy, privacy and justice. Practical concerns about insurability and discrimination may inhibit some at risk individuals from taking advantage of this powerful technology. There has been considerable effort already in the UK, Europe and the USA at the research and social levels to create protection for individuals found to carry genetic susceptibility to disease.
Bentzon, Diem Nguyen
A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....
Matro, Jennifer M; Ruth, Karen J; Wong, Yu-Ning; McCully, Katen C; Rybak, Christina M; Meropol, Neal J; Hall, Michael J
Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p testing (all p testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.
Hardiman, Karin M
Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.
Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.
Houlston, R S; Tomlinson, I P
The contribution of molecular genetics to colorectal cancer has been restricted largely to relatively rare inherited tumours and to the detection of germline mutations predisposing to these cancers. However, much is now also known about somatic events leading to colorectal cancer. A number of studies has been undertaken examining possible relations between genetic features and prognostic indices. While many of these studies are small and inconclusive, it is clear that a number of different pa...
Jensen, Lars Henrik; Rasmussen, Anders Aamann; Byriel, Lene
In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim...... of this study was to determine in detail how DNA methylation regulates MLH1 expression and impacts clinical management....
AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer ... Colorectal Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0273 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrea Burnett-Hartman 5d... cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s specific aims are as follows: 1) Estimate the risk of colorectal
Kune, G A; Kune, S; Watson, L F
The perceived or self-reported degree of 'religiousness' was obtained by interview from 715 colorectal cancer patients and 727 age/sex matched community controls, as part of a large, comprehensive population-based study of colorectal cancer incidence, aetiology and survival (The Melbourne Colorectal Cancer Study) conducted in Melbourne, Australia. Self-reported or perceived 'religiousness', as defined in the study, was a statistically significant protective factor [relative risk (RR) = 0.70, ...
Full Text Available Pneumatosis coli (PC is a rare condition of the gastrointestinal tract involving extraluminal gas confined within the bowel wall. We report the case of a 40-year-old gentleman presenting clinically and endoscopically with suspected colorectal cancer. In light of the patient’s red flag symptoms, and carpet of polyps seen endoscopically, surgical management by an anterior resection was performed with the patient making a successful recovery. Histological analysis of the resected specimen confirmed pneumatosis coli with no evidence of colonic neoplasia. Although PC can be an incidental finding in asymptomatic patients and considered a benign condition, it can also present as a life-threatening emergency with bowel necrosis and obstruction requiring emergency surgical intervention. Also, when PC mimics malignancy, surgical management is the most appropriate step to ensure that the diagnosis of cancer is not missed.
Bardram, Linda; Hansen, Thomas V O; Gerdes, Anne-Marie
Inactivating mutations in the CDH1 (E-cadherin) gene are the predisposing cause of gastric cancer in most families with hereditary diffuse gastric cancer (HDGC). The lifetime risk of cancer in mutation positive members is more than 80 % and prophylactic total gastrectomy is recommended. Not all...... mutations in the CDH1 gene are however pathogenic and it is important to classify mutations before this major operation is performed. Probands from two Danish families with gastric cancer and a history suggesting HDGC were screened for CDH1 gene mutations. Two novel CDH1 gene mutations were identified....... Hospital stay was 6-8 days and there were no complications. Small foci of diffuse gastric cancer were found in all patients-intramucosal in six and advanced in one. Preoperative endoscopic biopsies had revealed a microscopic cancer focus in two of the patients. Our data confirmed the pathogenic nature...
Song, Mingyang; Garrett, Wendy S; Chan, Andrew T
Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Hill, M J
In early epidemiological studies of diet and cancer the stress was on the search for causal factors. Population (ecological) studies tended to show a strong correlation between meat intake, particularly red meat, and the risk of colo-rectal cancer. They also tended to show meat to be strongly inversely correlated with cancers of the stomach and oesophagus and liver. Early case-control studies tended to support the postulated role for red meat in colo-rectal carcinogenesis, although more recent case-control studies, particularly those from Europe, have tended to show no relationship. The cohort studies in general failed to detect any relationship between meat intake and colo-rectal cancer risk. The available evidence points to the intake of protective factors such as vegetables and whole-grain cereals being the main determinants of colo-rectal cancer risk, with meat intake only coincidentally related.
Kampmeyer, Caroline; Nielsen, Sofie V.; Clausen, Lene
cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although...... by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes....
Pathological and biological aspects of colorectal cancer treatment. This thesis describes several pathological and biological aspects of colorectal cancer treatment. Different patient populations were investigated including patients with mobile rectal cancer enrolled in the Dutch TME trial, patients
Sijmons, Rolf H.; Hofstra, Robert M. W.
Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive
Yamada, T.; Ushio, K.; Hirota, T.
There is an increasing interest in the natural history of colorectal carcinoma, now that small polypoid lesions of the large intestine can be detected effectively by radiology and endoscopy. The problems of this histo- and morphogenesis of colorectal cancer have, however, remained unsettled because the observation of the sequential change of a lesion with time by follow-up radiology and/or endoscopy is impossible once its malignancy is proved. Clinically the retrospective review of radiographic findings in overlooked cases is the only means to evaluate the natural history of colorectal cancer. This paper attempts to estimate the growth rate of colorectal cancer, based on a retrospective review of radiographic findings of overlooked cases, and analyses of the radiographic features of small polypoid lesions which may develop into advanced cancers
M C Suresh Babu
Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.
Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F
BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....
Sarkar, Snigdha; Mukherjee, Ramanuj; Paira, Susil Kumar; Roy, Bipradas; Banerjee, Shubhabrata; Mukherjee, Saibal Kumar
Although colorectal cancer is a major cause of concern in the western population, recent studies are showing the incidence and mortality of colorectal cancer to be rapidly rising in Asia. The present study is an insight into the epidemiological profile of colorectal cancer of a representative Eastern Indian population. Over a period of three years, all histologically proved patients with colorectal cancer were assessed for age, sex, body mass index, dietary habits, socioeconomic status and stage of disease. Of a total of 168 patients male to female ratio was 1.7:1.The mean age of presentation was 47.01 years. Although colorectal cancer has been known as a disease of sedentary obese men, 41.66% of the patients were from a low socioeconomic rural set-up and 40.47% were involved in heavy physical labour with only 15% of being obese; 62% patients were harbouring a locally advanced disease at the time of presentation. The epidemiological pattern of colorectal cancer in India is different from that of the west as regards to earlier age of presentation, prevalence in low socio economic class with low fat diet and scanty meat intake.
Lashner, B.A.; Epstein, S.S.
Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. 143 references
Justin Timothy A
Full Text Available Abstract Background Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. Patients and methods A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. Results A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test. However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. Conclusion The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.
Joon, Aron; Brewster, Abenaa M.; Chen, Wei V.; Eng, Cathy; Shete, Sanjay; Casey, Graham; Schumacher, Fredrick; Lin, Yi; Harrison, Tabitha A.; White, Emily; Ahsan, Habibul; Andrulis, Irene L.; Whittemore, Alice S.; Ko Win, Aung; Schmidt, Daniel F.; Kapuscinski, Miroslaw K.; Ochs-Balcom, Heather M.; Gallinger, Steven; Jenkins, Mark A.; Newcomb, Polly A.; Lindor, Noralane M.; Peters, Ulrike; Amos, Christopher I.; Lynch, Patrick M.
Background Clustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype. Methods To identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at Pcolorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, Pdiscovery = 1.2E-04; rs7429100, Preplication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (P = 1.84E-06). Conclusion The results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of ROBO1, a potential tumor suppressor gene, merits further investigation. PMID:29698419
Pedro J. Tárraga López
developing colon cancer by 33% after eating less meat, while eating brown rice at least once a week reduces the risk of CRC by 40%. These associations suggest a dose-response effect. Frequently eating cooked vegetables, nuts, nuts, legumes and brown rice has been associated with a lower risk of colorectal polyps. High calcium intake provides a protective effect against distal colon and rectum tumors compared to the proximal colon. Increased intake of dairy and calcium reduces the risk of colon cancer. Regularly taking aspirin (ASA after being diagnosed with colon cancer is associated with less risk of dying from this cancer, especially among people who have COX-2 overexpressing tumors. However, these data do not contradict the data obtained on a possible genetic predisposition, even in sporadic or non-hereditary CRC. CRC is susceptible to detection because it is a serious health problem due to its high incidence and high associated morbidity / mortality. Conclusions: (1 Cancer is a global problem. (2 A modification of diet and lifestyle could reduce morbidity and mortality. (3 Early detection through screening improves prognosis and reduces mortality.
Colorectal cancer is one of the most common diagnosed cancers worldwide, and is the second most important cause of cancer mortality in Europe. The current TNM staging system used at the time of diagnosis is insufficient, as patients with the same tumor stage show wide variations in survival and
Colorectal cancer is predominantly a disease of the elderly. It is the second most common cancer in the UK and the third most common cause of cancer-related death. Surgical resection, either for cure or palliation, remains the mainstay of treatment.[1,2]. Long-term survival is related to the extent of disease at diagnosis.
Soemedi, Rachel; Maguire, Samantha; Murray, Michael F.; Monaghan, Sean F.
Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5′ and 3′ splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36%) of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing. PMID:29505604
Christy L Rhine
Full Text Available Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77% of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36% of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing.
This podcast is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer. Created: 7/5/2011 by Centers for Disease Control and Prevention (CDC). Date Released: 7/5/2011.
Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)
Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.
Bardhan, Kankana; Liu, Kebin
Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.
Bardhan, Kankana; Liu, Kebin
Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy
Full Text Available Colorectal cancer (CRC develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.
... in the colon and rectum is often called colorectal cancer. But in this brochure we use the term ... tests can be used to find polyps or colorectal cancer. Each can be used alone. Sometimes they are ...
Colorectal cancer prevention strategies can include avoiding known risk factors, having a healthy lifestyle, taking aspirin, and removing polyps. Learn more about preventing colorectal cancer in this expert-reviewed summary.
Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...
Bardi, G; Parada, L A; Bomme, L
Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....
A. R. Rama
Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.
Full Text Available Anuj Patel, Weijing Sun Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF-A, VEGF-B, and placental growth factor (PlGF; it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. Keywords: aflibercept, angiogenesis, colorectal cancer
Full Text Available Introduction: patients with sporadic colorectal cancer or cases associated with syndromes are at risk of having synchronous or metachronous cancer. Although it is an important subject, Brazilian data on the subject are scarce. Objective: to evaluate the incidence and epidemiological features in patients with synchro- nous and metachronous colorectal cancer in a reference service of proctology in the Rio Grande do Sul. Methods: cross-sectional observational study, performed between January and July 2012, analyzing all patients admitted in the service that met the inclusion criteria. A retrospective review of records was performed, noting demographic variables, comorbidi- ties and tumor-related variables. Results: 150 records were analyzed, of which 53.3% were males and mean age was 63 (± 13.01 years old. The most frequently found tumor location was the sigmoid colon and high rectum (50.67%, followed by the lower rectum (36%. Adenocarcinomas were the most prevalent histological subtype (88%, followed by epidermoid tumors (1.33%. Hereditary syndromes were identified in five patients (3.33%, with four being Familial adenomatous polyposis (FAP and one hereditary nonpolyposis colorectal cancer (HNPCC. Among the an- alyzed patients, four (2.67% had synchronous and one (0.67% had metachronous cancer. Conclusion: the incidence of synchronous and metachronous colorectal cancer was, respectively, 2.67% and 0.67%, results that corroborate those reported in international literature. Resumo: Introdução: pacientes com diagnóstico de câncer colorretal esporádico ou associado a sín- dromes correm risco de apresentar lesões sincrônicas ou metacrônicas. Embora seja rele- vante, há escassez de informações sobre o tema na literatura nacional. Objetivo: avaliar a incidência e o perfil epidemiológico dos pacientes com tumor colorretal sincrônico e metacrônico em um serviço de referência em proctologia do Rio Grande do Sul. Método: estudo
Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y
The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, pstatistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.
Bidel, S; Hu, G; Jousilahti, P; Antikainen, R; Pukkala, E; Hakulinen, T; Tuomilehto, J
The possible association between coffee consumption and risk of colorectal cancer has been extensively studied in the many populations. The aim of this study is to examine this relationship among Finns, who are the heaviest coffee consumers in the world. A total of 60 041 Finnish men and women who were 26-74 years of age and without history of any cancer at baseline were included in the present analyses. Their coffee consumption and other study characteristics were determined at baseline, and they were prospectively followed up for onset of colon and rectal cancer, emigration, death or until 30 June 2006. During a mean follow-up period of 18 years, 538 cases of colorectal cancer (304 cases of colon cancer and 234 cases of rectal cancer) were diagnosed. The multivariate-adjusted hazard ratio of colorectal cancer incidence for > or =10 cups of coffee per day compared with non-drinkers was 0.98 (95% CI, 0.47-2.03) for men (P for trend=0.86), 1.24 (95% CI, 0.49-3.14) for women (p for trend=0.83) and 1.03 (95% CI, 0.58-1.83) for men and women combined (P for trend=0.61). In this study, we found no association between coffee consumption and the risk of colorectal, colon and rectal cancer.
Colorectal cancer screening reduces deaths from the disease, yet about one-third of Americans aren’t up to date with screening. In this Cancer Currents blog post, learn what happened when people waiting for routine checkups could order their own screening test using a computer app.
Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...
Colorectal cancer (CRC) is one of the most common cancers in the Western world, with an estimated incidence of 148 810 cases in the USA in 2008, and about 50 000 deaths from this disease. If detected early, patients with disease localised to the colonic wall have a 5-year survival of 90%. The 5-year survival for patients ...
Colorectal cancer screening: World Gastroenterology Organisation/International Digestive Cancer Alliance Practice Guidelines. S Winawer, M Classen, R Lambert, M Fried, P Dite, K L Goh, F Guarner, D Lieberman, R Eliakim, B Levin, R Saenz, A G Khan, I Khalif, A Lanas, G Lindberg, M J O'Brien, G Young, J Krabshuis ...
Velculescu Victor E
Full Text Available Abstract Background Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Familial Adenomatous Polyposis (FAP. In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer. Methods Statistical analysis was performed using multipoint parametric and nonparametric linkage. Results Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL = 2.1. Conclusion The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.
Douglas K Rex
Full Text Available The two most recent guidelines for colorectal cancer screening are those of the Agency for Healthcare Policy and Research, and the American Cancer Society. The guidelines are similar in many regards and reflect current literature, consensus opinion and compromise between members of multidisciplinary panels. The emphasis of both guidelines is to increase the options available for colorectal cancer screening. Increasing choice should expand the attractiveness of colorectal cancer screening to more patients and physicians, and the development of guidelines should help compel payers to provide reimbursement for colorectal cancer screening. These guidelines are summarized and evaluated as they pertain to colorectal cancer screening.
Akbar, Fayyaz; Quyn, Aaron; Steele, Robert
Objectives Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons. Methods An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. Results Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area. Conclusions Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.
Nguyen, Kevin A; Syed, Jamil S; Shuch, Brian
The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals. Copyright © 2016 Elsevier Inc. All rights reserved.
Benson, Victoria S.; Atkin, Wendy S.; Green, Jane; Nadel, Marion R.; Patnick, Julietta; Smith, Robert A.; Villain, Patricia; Patnick, J.; Atkin, W. S.; Altenhofen, L.; Ancelle-Park, R.; Benson, V. S.; Green, J.; Levin, T. R.; Moss, S. M.; Nadel, M.; Ransohoff, D.; Segnan, N.; Smith, R. A.; Villain, P.; Weller, D.; Koukari, A.; Young, G.; López-Kostner, F.; Antoljak, N.; Suchánek, S.; Zavoral, M.; Holten, I.; Malila, N.; Salines, E.; Brenner, G.; Herszényi, L.; Tulassay, Z.; Rennert, G.; Senore, C.; Zappa, M.; Zorzi, M.; Saito, H.; Leja, M.; Dekker, E.; Jansen, J.; Hol, L.; Kuipers, E.; Kaminski, M. F.; Regula, J.; Sfarti, C.; Trifan, A.; Tang, C.-L.; Hrcka, R.; Binefa, G.; Espinàs, J. A.; Peris, M.; Chen, T. H.; Steele, R.; Pou, G.; Bisges, D.; Dwyer, D.; Groves, C.; Courteau, S.; Kramer, R.; Siegenthaler, K.; Lane, D.; Herrera, C.; Rogers, J.; Rojewski, M.; Wolf, Holly; Sung, J. J.; Ling, K.; Bryant, H.; Rabeneck, L.; Dale, J.; Sware, L.; Yang, H.; Viguier, J.; Von Karsa, L.; Kupcinskas, L.; Deutekom, M.; Törnberg, S.; Austoker, J.; Beral, V.; Monk, C.; Valori, R.; Watson, J.; Kobrin, S.; Pignone, M.; Taplin, S.
The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and
Shin, O. J.; Chin, S. Y.; Lee, K. S.; Park, S. S.
One hundred thirty two cases of the pathologically proven colorectal cancer at Korea Atomic Energy Research Institute Hospital in the period from January 1973 to June 1980 were analyzed radiologically and clinically. The results were as follows: 1. The colorectal cancer was prevalent in rectosigmoid area and in the fourth to seventh decade of life. 2. The clinical pictures were classified into two groups. The one was rectosigmoid cancer with bowel habit changes. The other was one with no specific symptoms or signs. The clinical pictures of the right colon cancer were rather indirected, chronic and systemic than those of the left one. 3. The roentgenological findings were classified into two groups. The one was rectum and left colon cancer with symmetrical annular narrowing and the other showed trumpet-like proximal dilatation. 4. The most frequent complication was intestinal obstruction. 5. The majority of colorectal cancer was adenocarcinoma. The squamous cell carcinoma and atypical cell carcinoma were most prevalent in rectum, but malignantly lymphoma often occurred in right colon. The rarest colorectal cancer was atypical cell carcinoma in rectum
Full Text Available Colorectal cancer (CRC is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA. Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6. Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3 had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.
Wang, Zhenjie; Uchida, Kazuhiro; Ohnaka, Keizo; Morita, Makiko; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.
Grady, William M.; Pritchard, Colin C.
The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577
Bouga, Helen; Tsouros, Isidoros; Bounias, Dimitrios; Kyriakopoulou, Dora; Stavropoulos, Michael S; Papageorgakopoulou, Nikoletta; Theocharis, Dimitrios A; Vynios, Demitrios H
Hyaluronidases belong to a class of enzymes that degrade, predominantly, hyaluronan. These enzymes are known to be involved in physiological and pathological processes, such as tumor growth, infiltration and angiogenesis, but their exact role in tumor promotion or suppression is not clear yet. Advanced colorectal cancer is associated with elevated amounts of hyaluronan of varying size. The aim of the present study was therefore to illuminate the importance of hyaluronidases in colon carcinoma progression. The patients' samples (macroscopically normal and cancerous) were subjected to sequential extraction with PBS, 4 M GdnHCl and 4 M GdnHCl - 1% Triton X-100. The presence of the various hyaluronidases in the extracts was examined by zymography and western blotting. Their expression was also examined by RT-PCR. Among hyaluronidases examined, Hyal-1, -2, -3 and PH-20 were detected. Their activity was higher in cancerous samples. Hyal-1 and Hyal-2 were overexpressed in cancerous samples, especially in advanced stages of cancer. Both isoforms were mainly extracted with PBS. Hyal-3 was observed only in the third extract of advanced stages of cancer. PH-20 was abundant in all three extracts of all stages of cancer. The expression of only Hyal-1 and PH-20 was verified by RT-PCR. A high association of hyaluronidases in colorectal cancer was observed. Each hyaluronidase presented different tissue distribution, which indicated the implication of certain isoforms in certain cancer stages. The results provided new evidence on the mechanisms involved in the progression of colorectal cancer
Lee, Bo In; Hong, Sung Pil; Kim, Seong Eun
Colorectal cancer is currently the second most common cancer among Korean males and the fourth most common among females. Since the majority of colorectal cancer case present following the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are vital methods in its prevention. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish national guidelines for colorectal cancer screening and polyp detection. The proposed guidelines have been developed by the Korean Multi-Society Task Force using evidence-based methods. Systematic reviews and meta-analyses have been used to form the statements contained in the guidelines. This paper discusses the epidemiology of colorectal cancers and adenomas in Korea as well as optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations.
Objective: To audit the completeness of histopathologic reports of Colorectal Cancer for prognostic information in a tertiary care hospital in the light of the minimum reporting standards for colorectal cancer resections recently proposed for use in Nigeria. Material and Methods: Twenty–five histopathology reports of colorectal ...
González-Acosta, Maribel; Del Valle, Jesús; Navarro, Matilde; Thompson, Bryony A; Iglesias, Sílvia; Sanjuan, Xavier; Paúles, María José; Padilla, Natàlia; Fernández, Anna; Cuesta, Raquel; Teulé, Àlex; Plotz, Guido; Cadiñanos, Juan; de la Cruz, Xavier; Balaguer, Francesc; Lázaro, Conxi; Pineda, Marta; Capellá, Gabriel
The clinical spectrum of germline mismatch repair (MMR) gene variants continues increasing, encompassing Lynch syndrome, Constitutional MMR Deficiency (CMMRD), and the recently reported MSH3-associated polyposis. Genetic diagnosis of these hereditary cancer syndromes is often hampered by the presence of variants of unknown significance (VUS) and overlapping phenotypes. Two PMS2 VUS, c.2149G>A (p.V717M) and c.2444C>T (p.S815L), were identified in trans in one individual diagnosed with early-onset colorectal cancer (CRC) who belonged to a family fulfilling clinical criteria for hereditary cancer. Clinico-pathological data, multifactorial likelihood calculations and functional analyses were used to refine their clinical significance. Likelihood analysis based on cosegregation and tumor data classified the c.2444C>T variant as pathogenic, which was supported by impaired MMR activity associated with diminished protein expression in functional assays. Conversely, the c.2149G>A variant displayed MMR proficiency and protein stability. These results, in addition to the conserved PMS2 expression in normal tissues and the absence of germline microsatellite instability (gMSI) in the biallelic carrier ruled out a CMMRD diagnosis. The use of comprehensive strategies, including functional and clinico-pathological information, is mandatory to improve the clinical interpretation of naturally occurring MMR variants. This is critical for appropriate clinical management of cancer syndromes associated to MMR gene mutations.
Petersen, Helle Vendel; Frederiksen, Birgitte Lidegaard; Lautrup, Charlotte Kvist; Lindberg, Lars Joachim; Ladelund, Steen; Nilbert, Mef
Dissemination of information on a genetically increased risk should according to guidelines primarily be family-mediated. Incomplete and incorrect information spread has, however, been documented and implies missed possibilities for prevention. In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer. To evaluate this approach, we investigated reactions and attitudes to unsolicited letters in 708 members of families with genetic predisposition and in 1600 individuals from the general population. Support for information letters was expressed by 78% of the family members and by 82% of the general population. Regarding route of information, 90% of family members preferred a letter to no information, 66% preferred information from the hospital rather than from family members and 40% preferred to obtain information from a close family member. Our results suggest that use of unsolicited information letters from the health care system may be a feasible and highly acceptable strategy to disseminate information to families at high risk of colorectal cancer.
Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian
Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion...... and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways. Newer aspects of microbiota and colorectal cancer include quorum sensing, biofilm formation, sidedness and effects/countereffects of microbiota...... and probiotics on chemotherapy. In the future, targeting the microbiota will probably be a powerful weapon in the battle against CRC as gut microbiology, genomics and metabolomics promise to uncover important linkages between microbiota and intestinal health....
Nakatsuka, H.; Ezaki, H.
Studies on autopsied and surgical cases of colorectal cancer in Hiroshima and Nagasaki atomic bomb (A-bomb) survivors have not shown a relationship to radiation. In a recent epidemiologic study made on a fixed population at the Radiation Effects Research Foundation (RERF), the risk of colon cancer was found to increase significantly with increasing radiation dose in both Hiroshima and Nagasaki, and also in both males and females. The dose effect for the cities and sexes combined was especially pronounced for cancer of the sigmoid colon. The effect of radiation was found to vary by age at the time of the bomb (ATB) and the effect was remarkable among those under age 20 ATB. The risk of rectal cancer was not found to increase significantly with radiation and the distribution of histological types for cancer of either the colon or rectum was unrelated to radiation dose. The effect of A-bomb exposure on the postoperative survival rate for colorectal cancer patients was studied. No difference by radiation dose could be demonstrated. In Japan, the incidence of colorectal cancer, and of colon cancer in particular, has been increasing. Therefore, close attention should be paid to changes occuring in A-bomb survivors
Nakatsuka, Hirofumi; Ezaki, Haruo.
Studies on autopsied and surgical cases of colorectal cancer in Hiroshima and Nagasaki atomic bomb (A-bomb) survivors have not shown a relationship to radiation. In a recent epidemiologic study made on a fixed population at the Radiation Effects Research Foundation (RERF), the risk of colon cancer was found to increase significantly with increasing radiation dose in both Hiroshima and Nagasaki, and also in both males and females. The dose effect for the cities and sexes combined was especially pronounced for cancer of the sigmoid colon. The effect of radiation was found to vary by age at the time of the bomb (ATB) and the effect was remarkable among those under age 20 ATB. The risk of rectal cancer was not found to increase significantly with radiation and the distribution of histological types for cancer of either the colon or rectum was unrelated to radiation dose. The effect of A-bomb exposure on the postoperative survival rate for colorectal cancer patients was studied. No difference by radiation dose could be demonstrated. In Japan, the incidence of colorectal cancer, and of colon cancer in particular, has been increasing. Therefore, close attention should be paid to changes occurring in A-bomb survivors. (author)
Beebe-Dimmer, Jennifer L; Yee, Cecilia; Paskett, Electra; Schwartz, Ann G; Lane, Dorothy; Palmer, Nynikka R A; Bock, Cathryn H; Nassir, Rami; Simon, Michael S
Evidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated. Analyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White). Of 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54). Our findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers.
Kurotani, Kayo; Budhathoki, Sanjeev; Joshi, Amit Man; Yin, Guang; Toyomura, Kengo; Kono, Suminori; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
Few studies have addressed the relation between dietary patterns and colorectal cancer in Japan. We investigated dietary patterns in relation to colorectal cancer risk in a community-based case-control study. The association with dietary patterns was also examined for different sites of colorectal cancer. Data were derived from the Fukuoka Colorectal Cancer Study, including 800 cases and 775 controls interviewed from September 2000 to December 2003. The cases were admitted to one of the participating hospitals for the first surgical treatment during this period. We identified dietary patterns using principal component analysis of intakes of twenty-nine items of food groups and specific foods. Quartile categories of each dietary pattern were used, and non-dietary lifestyle factors and total energy intake were adjusted for in the analysis. We identified three dietary patterns: prudent, high-fat and light-meal patterns. The prudent dietary pattern characterised by high intakes of vegetables, fruits, seafoods and soya foods showed a nearly significant protective association with the overall risk of colorectal cancer (trend P = 0.054), and it was statistically significantly related to a decreased risk of distal colon cancer (trend P = 0.002), but not to that of either proximal colon or rectal cancer. The high-fat and light-meal dietary patterns were not materially related to the overall or site-specific risk of colorectal cancer. In summary, a prudent dietary pattern was associated with a decreased risk of colorectal cancer, especially with that of distal colon cancer, in a fairly large case-control study in Japan.
D. Cruz-Bustillo Clarens
Full Text Available Colorectal tumours constitute an excellent system to study carcinogenesis and the molecular events implicated in the development of cancer. Attending to the way it is transmitted, colorectal cancer may appear in one of three forms: sporadic, familial, and hereditary. The sporadic form is most common and has no familial or hereditary associated factor thus far, while familial and hereditary forms show the same inheritance pattern. Hereditary colorectal cancers develop by means of defined stages that go from lesions in the crypt of the colon through adenomas to manifest cancer. They are characterised by the accumulation of multiple mutations in tumour suppressor genes and oncogenes that affect the balance between cell proliferation and apoptosis. The colorectal carcinogenesis pathway is not unique and there are probably several ways for the initiation, development and progression of colorectal tumours.Los tumores colorrectales constituyen un excelente sistema para estudiar la carcinogénesis y los eventos moleculares involucrados en el desarrollo de un tumor. El cáncer colorrectal puede presentarse en tres formas, según su forma de transmisión: esporádico, familiar y hereditario. La forma esporádica que es la mayoritaria, no tiene hasta el momento ningún factor familiar o hereditario asociado, mientras que las formas familiares y hereditarias siguen un patrón de herencia en la propensión familiar a padecerlo. Los cánceres colorrectales hereditarios se desarrollan mediante etapas definidas que van desde lesiones en la cripta del colon a través de adenomas hasta manifestar el cáncer y se caracterizan por la acumulación de múltiples mutaciones en genes supresores de tumor y oncogenes que afectan el balance entre la proliferación celular y la apoptosis. La vía de carcinogénesis colorrectal no es una sola y probablemente existan varios caminos para el inicio, desarrollo y progresión de un tumor colorrectal.
Svobodová, Š.; Topolčan, O.; Holubec jr., L.; Levý, M.; Pecen, Ladislav; Svačina, Š.
Roč. 31, č. 1 (2011), s. 373-378 ISSN 0250-7005 Institutional research plan: CEZ:AV0Z10300504 Keywords : colorectal cancer * biological activity * prognosis * tumor markers * angiogenetic factors * metalloproteinases * adhesion molecules Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011
Cintin, C; Johansen, J S; Christensen, Ib Jarle
related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three...
Pfeiffer, Per; Qvortrup, Camilla; Tabernero, Josep
Recent modalities and strategies have increased the complexity of treatment choice in patients with colorectal cancer (CRC), and therefore all cases should be assessed at a multidisciplinary conference. Adjuvant chemotherapy for 6 months increases the chance of cure by absolutely 5 % in stage II...
Tørring, Marie Louise; Frydenberg, Morten; Hamilton, William
Objective To test the theory of a U-shaped association between time from the first presentation of symptoms in primary care to the diagnosis (the diagnostic interval) and mortality after diagnosis of colorectal cancer (CRC). Study Design and Setting Three population-based studies in Denmark...
Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa
Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...
Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H
BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival...
CDCâs Dr. Lisa Richardson explains why she got tested for colorectal cancer when she turned 50 years old. . Created: 2/29/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP). Date Released: 2/29/2016.
Maiello, E; Giuliani, F; Gebbia, V; Piano, A; Agueli, R; Colucci, G
In recent years, the introduction of targeted therapies into clinical practice seems to offer incremental benefits in the treatment of metastatic colorectal cancer (mCRC), mainly when they are employed in combination with optimal chemotherapy and/or radiotherapy. In this paper, we focus on Cetuximab and its role in the treatment of mCRC.
Jagt, M.F.P. van der; Wobbes, T.; Strobbe, L.J.; Sweep, F.C.; Span, P.N.
Metalloproteinases (MPs) such as the matrix metalloproteinases (MMPs) and adamalysins (ADAMs and ADAMTS) are expressed in various stages of colorectal cancer (CRC), and some correlate with survival and prognosis. The MPs are regulated by various factors including EMMPRIN, TIMPs, and RECK. In
Full Text Available Background: Colorectal cancer is one of the most frequent cancers in developed countries and Slovenia, and the incidence is still rising. Groups of people with higher risk for colorectal cancer are well defined. Among them are patients with inflammatory bowel disease. The risk is highest in patients in whom whole large bowel is affected by inflammation, it rises after 8 to 10 years and increases with the duration of the disease. Precancerous lesion is a displastic, chronically inflammed mucosa and not an adenoma as in cases of sporadic colorectal carcinoma.Conclusions: Many studies suggest that the influence of genetic factors differs between sporadic and inflammatory bowel disease related colorectal cancer. Symptomatic patients at the time of diagnosis have a much worse prognosis. The goal of prevention programes is therefore discovering early precancerous lesions. Established screening protocols are based on relatively frequent colonoscopies which are inconvinient for the patient as well as the endoscopist. Use of specific genetic markers, mutations of candidate genes, as a screening method and a prognostic predictor could greatly lighten therapeutic decisions.
Chandel, Shammy; Akhtar, Reyhan; Sarotra, Pooja; Medhi, Bikash
The purpose of this study was the colonoscopic detection and removal of neoplasia from the colorectum to prevent the development of colorectal cancer. Various online medical databases were searched such as PubMed, ACS, NCI, NIH, WHO, etc. for relevant publications and clinical trials for new developments in colonoscopic devices that are intended for diagnostic visualization and therapeutic interventions of the digestive tract. HD colon and I-Scan both has shown to increase the detection of sporadic adenomas with high quality. Third Eye Retroscope confers the backward view of colon, but aeroscope screens the entire colon in 30-60 min. Narrow-band imaging enhances mucosal and vascular details through the color differentiation of precancerous or cancerous polyp, compared to white light colonoscopy. The PillCam Colon Capsule is another new technique which is easily inserted and painless. In case of chemotherapy, Therasphere with Yttrium-90 has good results in the treatment of colorectal adenocarcinoma metastasis. Radiofrequency ablation is a good technique for tumors ablation and Staple Line Reinforcement prevents the leak during and post-surgery of colon. FOBT is much more sensitive and cheaper test for colorectal cancer screening. Registered clinical trials have shown promising results for neoplasia detection by I-Scan, TER, and NBI imaging techniques will change current colonoscopic practice in colorectal cancer screening. However, more studies and inventions are required for improving the patient safety and efficacy.
Soldatkina, N V; Kit, O I; Gevorkyan, Yu A; Milakin, A G
to define some clinical characteristics of synchronous and metachronous colorectal cancer (CRC). The investigation was concerned with the data of 150 patients with T1-4N0-2M0-1 multiple primary CRC. The clinical, biological, and morphological characteristics of synchronous and metachronous tumors were analyzed. Multiple primary tumors were 6.01% of all the cases of CRC. There was a preponderance of synchronous CRC (63.75%) with the tumor localized in the sigmoid colon and rectum. In women, synchronous colorectal tumors were more often concurrent with breast tumors; metachronous ones were detected after treatment for genital tumors. In men, synchronous colorectal tumors were more frequently concurrent with kidney cancer; metachronous ones were identified after treatment for gastric cancer. The found characteristics of multiple primary colorectal tumors may be taken in account in programs for both primary diagnosis and follow-up after treatment for malignant tumors, which will be able to improve the early detection of cancer patients and their treatment results.
Custers, J.A.E.; Gielissen, M.F.M.; Janssen, S.H.; Wilt, J.H.W. de; Prins, J.B.
PURPOSE: Although long-term colorectal cancer (CRC) survivors generally report a good quality of life, fear of cancer recurrence (FCR) remains an important issue. This study investigated whether the Cancer Worry Scale (CWS) can detect high FCR, the prevalence, and characteristics of FCR in CRC
Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which
Lynch, Henry T
To date we have seventy-three Hereditary Breast/Ovarian Cancer families with identified BRCA1 or BRCA2 genetic mutations, wherein 24 additional cases of slides and tissue blocks have been retrieved...
Brim, Hassan; Ashktorab, Hassan
Genome-wide studies are increasingly becoming a must, especially for complex diseases such as cancer where multiple genes and diverse molecular mechanisms are known to be involved in genes’ function alteration. In this review, we report our latest genomic and epigenomic findings in African-American colorectal cancer patients. This population suffers a higher burden of the disease and most investigators in this field are looking for the underlying genetic and epigenetic targets that might be r...
Hossein Ali Nikbakht; Nayyereh Amini Sani; Mohamad Asghari Jafarabadi; Seyed Reza Hosseini
Background: Colorectal cancer has a significant impact on physical, mental and social discomfort of patients. The aim of this study was to assess different aspects of health-related quality of life and its association with demographic characteristics and some clinical features in colorectal cancer survivors in the city of Babol. Methods: This cross-sectional study was conducted in 2013 among 120 colorectal cancer survivors identified in the cancer registry from 2007 to 2012. A questionnair...
den Heijer, Mariska; Seynaeve, Caroline; Vanheusden, Kathleen; Duivenvoorden, Hugo J; Bartels, Carina C M; Menke-Pluymers, Marian B E; Tibben, Aad
Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.
Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda
The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.
Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei
Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.
Dagan, E; Gershoni-Baruch, R
Genetic counseling and risk assessment, given to women with a family history of breast/ovarian cancer, are regularly based on pedigree analysis. In the Ashkenazi Jewish population, hereditary breast/ovarian cancer is mainly attributed to three founder mutations, namely, 185delAG, 5382insC, and 6174delT, in BRCA1/2 genes. The overall frequency of these mutations, in the Jewish Ashkenazi population, is as high as 2.5%. Based on clinical and family history data, the results of BRCA molecular testing, in Ashkenazi individuals at risk, are appropriately anticipated in most cases. Here we report on five families, in which the segregation of BRCA1/2 mutations, in affected and unaffected family members, was unexpected, emphasizing the need to test, for founder mutations, every Ashkenazi individual at risk, irrespective of the genotype of affected family members. Ultimately, risk assessments and recommendations, in Ashkenazi women, should be invariably based on the results of genetic testing.
Lü, Bingjian; Xu, Jing; Lai, Maode; Zhang, Hao; Chen, Jian
Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers
Balog, Crina I. A.; Stavenhagen, Kathrin; Fung, Wesley L. J.; Koeleman, Carolien A.; McDonnell, Liam A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred
Colorectal cancer is the third most common cancer worldwide with an annual incidence of ∼1 million cases and an annual mortality rate of ∼655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. PMID:22573871
Colorectal cancer is one of the most common malignant tumors. There are many tumor markers for detecting colorectal cancer, some of which have been widely used in clinical area. However, still lack an ideal tumor marker of colorectal cancer. In this review, we simply characterized some common tumor markers including carcinoembryonic antigen, CA19-9, CA50, CA242 etc and their dignostic value. And here we discussed some combined detecting procedures which improve diagnostic accuracy of colorectal cancer. In addition, with the development of the biomoleculer technique, some newly discovered tumor markers and genetic marekers have gained great progress in the research of colorectal cancer, and will become a promissing technique in the diagnosis of colorectal cancer. (authors)
Amini, A.Q.; Samo, K.A.; Memon, A.S.
Objective: To promote awareness regarding increased occurrence of colorectal cancer in younger population and its clinicopathological features compared to older patients. Methods: The cross-sectional study was conducted from February 2010 to January 2011 on patients with diagnosis of colorectal carcinoma admitted through emergency or outpatient departments to Surgical Unit 5, Civil Hospital, Karachi. Data regarding age, gender, presentation, site of tumour, surgery performed and Dukes staging was collected and analysed. Results: A total of 23 patients were operated during the study period: 13 (56.52%) males and 10 (43.47%) females. Of them 12 (52.17%) were below the age of 40 years, while 3 (13.04%) patients were in the 11-20 age group. In 7 (30.4%) patients, tumour was irresectable at the time of presentation so a palliative procedure (diversion colostomy or ileostomy) was performed. There was a higher proportion of younger patients with metastatic disease at the time of presentation (n=9; 75%) while 10 out of 12 patients in the younger age group (83.3%) had a tumour of left colon, particularly rectum. Conclusion: Although colorectal cancer is usually a disease of older patients, it is increasingly becoming more common in younger population. Data suggests a leftward distribution for colorectal carcinoma and that younger patients present with more advanced disease and poorer prognosis. (author)
Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...... detected in 7.5% of the patients and in 37% of these cases the metastatic spread was confined to the lungs. The prevalence of SPCM increased with the implementation of thoracic CT in CRC staging. SPCM impaired survival significantly and was associated with increasing age and rectal cancer. Resection...
Full Text Available Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI of sporadic, HNPCC, and familial hyperplastic polyps (HPs. Methods. Methylation-specific PCR (MSP and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining. Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P=.186 Chi2. The familial group demonstrated significantly less over all methylation levels (P=.004 Chi2. Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting.
Isinger-Ekstrand, Anna; Therkildsen, Christina; Bernstein, Inge
-cadherin in 80% with strong correlation between these markers (P = 0.001). Nuclear ß-catenin staining was detected in 19% of the tumors. Overexpression of TCF-4, which is activated by ß-catenin, was found in 89% and downregulation of PTEN, which suppresses nuclear accumulation of ß-catenin, was present in 54...
Isinger-Ekstrand, Anna; Therkildsen, Christina; Bernstein, Inge
-cadherin in 80% with strong correlation between these markers (P = 0.001). Nuclear β-catenin staining was detected in 19% of the tumors. Overexpression of TCF-4, which is activated by β-catenin, was found in 89% and downregulation of PTEN, which suppresses nuclear accumulation of β-catenin, was present in 54...
Poaty, Henriette; Aba Gandzion, Chandra; Soubeyran, Isabelle; Gassaye, Déby; Peko, Jean Félix; Nkoua Bon, Jean Bernard; Gombé Mbalawa, Charles
We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
Colorectal cancer (CRC) is a public health challenge in developed countries and ... of this cancer in sub-Saharan Africa, Middle East, South Asia and the Caribbean. ... populations from low risk regions to countries in North America, Europe and ... risk of colorectal cancer (CRC) in their newly found environment as a result of ...
Background: Colorectal cancer remains a major health problem especially in developed countries where it ranks as the third most common cause of cancer in both men and women. Though incidence of colorectal cancer is low in Nigeria and other developing countries, outcome of treatment remains poor due largely to late ...
Background: Colorectal cancer is a major cause of cancer death worldwide, and the prevalence in Nigeria appears to be increasing due to a shift to western diets. We undertook a retrospective analysis of colorectal cancers seen at the University of Benin Teaching Hospital, Benin City from January 1983 to December 2002.
In the Netherlands approximately 5% of all people will develop colorectal cancer during his or her life. The rapid development of individualized therapy for cancer patients has led to an increased interest in tumor subtypes. Currently, colorectal cancer patients are treated in the same way
Purpose: Colorectal cancer (CRC) is among the top five cancers afflicting both men and women globally. Once predominantly a Western disease, it has begun to rise in Asian countries as well. This systematic review aims to compile and analyze the various barriers towards colorectal cancer screening in Asia, and to ...
Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord
In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; Peosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising
Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.
Colorectal cancer is one of the most common malignant tumors in China. In 2012 one million thirty six thousand cases of colorectal cancer were diagnosed all over the world, two hundred fifty three thousand cases were diagnosed in China (accounted for 18.6%). China has the largest number of new cases of colorectal cancer in the world. Colorectal cancer has becoming a serious threat of Chinese residents' health. In 2010, the National Ministry of Health organized colorectal cancer expertise of the Chinese Medical Association to write the "Chinese Protocol of Diagnosis and Treatment of Colorectal Cancer" (2010edition), and publish it publicly. In recent years, the National Health and Family Planning Commission has organized experts to revised the protocol 2 times: the first time in 2015, the second time in 2017. The revised part of "Chinese Protocol of Diagnosis and Treatment of Colorectal Cancer" (2017 edition) involves new progress in the field of imaging examination, pathological evaluation, surgery, chemotherpy and radiotherapy. The 2017 edition of the protocol not only referred to the contents of the international guidelines, but also combined with the specific national conditions and clinical practice in China, and also included many evidence-based clinical data in China recently. The 2017 edition of the protocol would further promote the standardization of diagnosis and treatment of colorectal cancer in China, improve the survival and prognosis of patients, and benefit millions of patients with colorectal cancer and their families.
Rudkjøbing, Laura Aviaja; Eiberg, Hans; Mikkelsen, Hanne Birte
Hereditary colorectal cancer accounts for approximately 30 % of all colorectal cancers, but currently only 5 % of these families can be explained by highly penetrant, inherited mutations. In the remaining 25 % it is not possible to perform a gene test to identify the family members who would...... benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family...... areas on chromosome 2 and chromosome 11 with the highest possible LOD scores of 2.6. Two other studies have identified 11q24 as a candidate area for colorectal cancer susceptibility and this area is supported by our results....
Nordholm-Carstensen, Andreas; Jorgensen, Lars N; Wille-Jørgensen, Peer A
BACKGROUND: The clinical significance of indeterminate pulmonary nodules (IPN) at staging computed tomography (CT) for colorectal cancer (CRC), and the optimal diagnostic approach, are debated. This study aimed to analyse variability in radiologists' detection of IPN at staging CT for CRC. METHODS......: All patients with CRC referred to our center between 2006 and 2011 were included. Primary staging CT scans were re-evaluated by an experienced thoracic radiologist whose findings were entered into a dedicated database and merged with data from the Danish Colorectal Cancer Group database, the National...... investigated radiological characteristics or clinicopathological factors were significantly associated with malignancy of IPN. CONCLUSION: The characterization of pulmonary findings on staging CT for CRC varied greatly between the radiologists, and double-reading of scans with IPN is recommended prior...
Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F
BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....
Temraz, Sally; Mukherji, Deborah; Shamseddine, Ali
The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the "proof of principle" that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.
Full Text Available The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2, nuclear factor kappa B (NF-κB, survivin and insulin-like growth factor-I (IGF-I. Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.
Full Text Available Most of the colorectal cancer (CRC cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability, CIN (chromosomal instability, and CIMP (CpG island methylator phenotype. CIN occurs in 80–85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype.
Rainey, J. B.
Cogent epidemiological and experimental data implicate bile acids as endogenous co-carcinogens in colorectal cancer. A series of experiments was designed to test the ability of sodium deoxycholate (SDC) to promote intestinal hyperplasia and neoplasia in rats (n = 265). The intermediary role of faecal anaerobes was explored in animals receiving oral metronidazole. Intrarectal instillation of SDC trebled tumour yield in functioning large bowel and increased both crypt depth and crypt cell produ...
Cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer (mCRC). As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. More recent studies show promising...
Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio
Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348
Moghimi-Dehkordi, Bijan; Safaee, Azadeh; Zali, Mohammad R
Gastric and colorectal cancers are the most common gastrointestinal malignancies in Iran. We aim to compare the survival rates and prognostic factors between these two cancers. We studied 1873 patients with either gastric or colorectal cancer who were registered in one referral cancer registry center in Tehran, Iran. All patients were followed from their time of diagnosis until December 2006 (as failure time). Survival curves were calculated according to the Kaplan-Meier Method and compared by the Log-rank test. Multivariate analysis of prognostic factors was carried out using the Cox proportional hazard model. Of 1873 patients, there were 746 with gastric cancer and 1138 with colorectal cancer. According to the Kaplan-Meier method 1, 3, 5, and 7-year survival rates were 71.2, 37.8, 25.3, and 19.5%, respectively, in gastric cancer patients and 91.1, 73.1, 61, and 54.9%, respectively, in patients with colorectal cancer. Also, univariate analysis showed that age at diagnosis, sex, grade of tumor, and distant metastasis were of prognostic significance in both cancers ( P < 0.0001). However, in multivariate analysis, only distant metastasis in colorectal cancer and age at diagnosis, grade of tumor, and distant metastasis in colorectal cancer were identified as independent prognostic factors influencing survival. According to our findings, survival is significantly related to histological differentiation of tumor and distant metastasis in colorectal cancer patients and only to distant metastasis in gastric cancer patients. (author)
Qi, Lu; Ding, Yanqing
Metastasis is a key factor that affects the survival and prognosis of colorectal cancer patients. To elucidate molecular mechanism associated with the metastasis of colorectal cancer, genes related to the metastasis time of colorectal cancer were screened. Then, a network was constructed with this genes. Data was obtained from colorectal cancer expression profile. Molecular mechanism elucidated the time of tumor metastasis and the expression of genes related to colorectal cancer. We found that metastasis-promoting and metastasis-inhibiting networks included protein hubs of high connectivity. These protein hubs were components of organelles. Some ribosomal proteins promoted the metastasis of colorectal cancer. In some components of organelles, such as proteasomes, mitochondrial ribosome, ATP synthase, and splicing factors, the metastasis of colorectal cancer was inhibited by some sections of these organelles. After performing survival analysis of proteins in organelles, joint survival curve of proteins was constructed in ribosomal network. This joint survival curve showed metastasis was promoted in patients with colorectal cancer (P = 0.0022939). Joint survival curve of proteins was plotted against proteasomes (P = 7 e-07), mitochondrial ribosome (P = 0.0001157), ATP synthase (P = 0.0001936), and splicing factors (P = 1.35e-05). These curves indicate that metastasis of colorectal cancer can be inhibited. After analyzing proteins that bind with organelle components, we also found that some proteins were associated with the time of colorectal cancer metastasis. Hence, different cellular components play different roles in the metastasis of colorectal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.
Cintin, C; Johansen, J S; Christensen, Ib Jarle
related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three......YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been...
Vilar, Eduardo; Mork, Maureen E; Cuddy, Amanda; Borras, Ester; Bannon, Sarah A; Taggart, Melissa W; Ying, Jun; Broaddus, Russell R; Luthra, Rajyalakshmi; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; You, Yi-Qian Nancy
Lynch syndrome is the most common Mendelian disorder predisposing persons to hereditary colorectal cancer. Carriers of MSH6 mutations constitute less than 10% of the total of cases with Lynch syndrome and present with a weaker clinical phenotype, including low levels of microsatellite instability (MSI-L) in colorectal tumors. The frequency of MSH6 mutation carriers among patients presenting with MSI-L colorectal cancer has yet to be determined, as has the appropriate genetic workup in this context. We have reviewed here the clinicopathologic characteristics, immunohistochemistry, and genetic testing results for 71 patients at a single institution diagnosed with MSI-L colorectal cancers. Of 71 patients with MSI-L tumors, 21 underwent genetic testing for MSH6 mutations, three of whom presented with loss of staining of MSH6 and only one of whom carried a pathogenic germline MSH6 mutation in exon 4 (c.2677_2678delCT; p.Leu893Alafs*6). This latter patient had a significant family history of cancer and had a rectal primary tumor that showed instability only in mononucleotide markers. In this cohort of MSI-L patients, we detected no notable clinicopathologic or molecular characteristic that would help to distinguish a group most likely to harbor germline MSH6 mutations. Therefore, we conclude that the prevalence of MSH6 mutations among patients with MSI-L tumors is very low. Microsatellite instability analysis combined with immunohistochemistry of mismatch repair proteins adequately detects potential MSH6 mutation carriers among MSI-L colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.
AD_________________ Award Number: W81XWH-13-1-0198 TITLE: The Role of Akt Isoforms in Colorectal Cancer PRINCIPAL INVESTIGATOR: Jatin Roper...CONTRACT NUMBER The Role of Akt Isoforms in Colorectal Cancer 5b. GRANT NUMBER W81XWH-13-1-0198 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...substantially reduces colorectal tumorigenesis in our genetically engineered mouse model. We also successfully ablated novel downstream targets of Akt in our
Cremers, R.G.H.M.; Aben, K.K.H.; Oort, I.M. van; Sedelaar, J.P.M.; Vasen, H.F.A.; Vermeulen, S.H.; Kiemeney, L.A.L.M.
BACKGROUND: The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form
Rojas, Oscar A; Martinez, Carlos E; Escobar, Jaime; Sanchez, William; Serrano, Juan M
Currently, early colorectal cancer (ECC) constitutes only 10% of the total of diagnosed colorectal malignancy. This proportion is expected to show an important increase with the different screening protocols that are on the way, together with recent advances in diagnostic and therapeutic colonoscopy. We compare the histopathologic spectrum of ECC from the western and Japanese viewpoint, defining the anatomopathologic characteristics of this lesions, together with the natural history and new classification and staging systems; variables which are all oriented to establish the grade of local invasion and risk of nodal spread. The knowledge and integral analysis of the different biologic, clinical, histological and endoscopic characteristics of ECC, will determine the most rational individual therapeutic pathway from the prognostic point of view
Feb 6, 2013 ... This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%. Objectives. The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the. Northern Cape.
Full Text Available Abstract Background Data comparison between SEER and EUROCARE database provided evidence that colorectal cancer survival in USA is higher than in European countries. Since adjustment for stage at diagnosis markedly reduces the survival differences, a screening bias was hypothesized. Considering the important role of primary care in screening activities, the purpose of the study was to investigate the colorectal cancer screening awareness among Hellenic physicians. Methods 211 primary care physicians were surveyed by mean of a self-reported prescription-habits questionnaire. Both physicians' colorectal cancer screening behaviors and colorectal cancer screening recommendations during usual check-up visits were analyzed. Results Only 50% of physicians were found to recommend screening for colorectal cancer during usual check-up visits, and only 25% prescribed cost-effective procedures. The percentage of physicians recommending stool occult blood test and sigmoidoscopy was 24% and 4% respectively. Only 48% and 23% of physicians recognized a cancer screening value for stool occult blood test and sigmoidoscopy. Colorectal screening recommendations were statistically lower among physicians aged 30 or less (p = 0.012. No differences were found when gender, level and type of specialization were analyzed, even though specialists in general practice showed a trend for better prescription (p = 0.054. Conclusion Contemporary recommendations for colorectal cancer screening are not followed by implementation in primary care setting. Education on presymptomatic control and screening practice monitoring are required if primary care is to make a major impact on colorectal cancer mortality.
Introduction: Colorectal cancer is a major cause of morbidity and mortality globally and its incidence is increasing in developing countries. This study determined the incidence, clinical features and the histopathological patterns of colorectal cancer at Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Methods: A ...
Archampong, David; Borowski, David; Wille-Jørgensen, Peer
A large body of research has focused on investigating the effects of healthcare provider volume and specialization on patient outcomes including outcomes of colorectal cancer surgery. However there is conflicting evidence about the role of such healthcare provider characteristics in the management...... of colorectal cancer....
Background The incidence of colorectal cancer in Africa is increasing. True data on clinical outcomes of the disease is hampered by follow up challenges. Method Follow up data of 233 patients treated for colorectal cancer between 2005 and 2010 at various Nairobi hospitals were evaluated. The primary outcome was ...
To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...
Becker, N. [Deutsches Krebsforschungszentrum Heidelberg (Germany)
Colorectal tumors are among the most frequently encountered forms of cancer worldwide. With approximately 57,000 new cases every year, they represent the most frequent type of cancer in Germany, ranking before breast cancer (approximately 46,000) and lung cancer (approximately 37,000). Although global incidence is on the rise, in Germany it is only increasing among men, but not among women. The mortality rate (approximately 26,500 deaths annually) in Germany has declined among men for about the past 10 years and among women for about the past 20 years.The most important risk factors are familial history of colorectal and other tumors as well as lifestyle factors such as nutrition, obesity, inactivity,and smoking.Lifestyle-related risks offer a broad area for implementing primary preventive measures, which have not yet been adequately exhausted. Several proven (fecal occult blood test) and probably effective (endoscopic) methods are available for secondary prevention. Consistent encouragement of these possibilities for prevention could reduce incidence and mortality substantially and render colorectal tumors less frequent. (orig.) [German] Kolorektale Tumoren gehoeren weltweit zu den haeufigsten Krebsarten und sind mit jaehrlich ca.57000 Neuerkrankungsfaellen vor Brustkrebs (ca. 46000) und Lungenkrebs (ca. 37000) die haeufigste Krebsart in Deutschland.Waehrend die Inzidenz weltweit steigt, nimmt sie in Deutschland nur bei Maennern,nicht aber bei Frauen zu.Die Mortalitaet (jaehrlich ca.26500 Todesfaelle) geht hierzulande bei Maennern seit ca.10 Jahren, bei Frauen seit ca.20 Jahren zurueck. Die bedeutendsten Risikofaktoren sind familiaere Vorgeschichte an kolorektalen und anderen Tumoren sowie Lebensstilfaktoren wie Ernaehrung, Uebergewicht,Bewegungsmangel und Rauchen.Die lebensstilbedingten Risiken bieten breiten Raum fuer primaere Praevention, der bisher nur unzureichend ausgeschoepft ist.Auch fuer sekundaere Praevention stehen mehrere nachgewiesenermassen (Test auf
Bolocan, A; Ion, D; Ciocan, D N; Paduraru, D N
Colorectal cancer (CRC) is an important public health problem; it is a leading cause of cancer mortality in the industrialized world, second to lung cancer: each year there are nearly one million new cases of CRC diagnosed worldwide and half a million deaths (1). This review aims to summarise the most important currently available markers for CRC that provide prognostic or predictive information. Amongst others, it covers serum markers such as CEA and CA19-9, markers expressed by tumour tissues, such as thymidylate synthase, and also the expression/loss of expression of certain oncogenes and tumour suppressor genes such as K-ras and p53. The prognostic value of genomic instability, angiogenesis and proliferative indices, such as the apoptotic index, are discussed. The advent of new therapies created the pathway for a personalized approach of the patient. This will take into consideration the complex genetic mechanisms involved in tumorigenesis, besides the classical clinical and pathological stagings. The growing number of therapeutic agents and known molecular targets in oncology lead to a compulsory study of the clinical use of biomarkers with role in improving response and survival, as well as in reducing toxicity and establishing economic stability. The potential predictive and prognostic biomarkers which have arisen from the study of the genetic basis of colorectal cancer and their therapeutical significance are discussed. RevistaChirurgia.
logical types of colorectal cancer cases presented to Ibn Sina specialized hospital. ... Abdominal pain. Tenesmus. Weight loss. Abdominal distension. Anal pain ... Male sex. 23. 18. 31. 21. Family history 8. 1. 6. 5. Rectal cancer. 26. 9. 29. 26.
Storm, Line; Christensen, Ib J; Jensenius, Jens C
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Lack of symptoms results in late detection and increased mortality. Inflammation, including complement activation, plays an important role in tumorigenesis. EXPERIMENTAL DESIGN: The concentrations of nine proteins...
Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer.
This 60 second Public Service Announcement (PSA) is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer.
Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef
BACKGROUND: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other...... than MMR proteins. METHODS: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. RESULTS: Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch...... syndrome (p Lynch syndrome tumors compared with FCCTX tumors (p = 0.001,
Guerra, Joana; Pinto, Carla; Pinto, Diana; Pinheiro, Manuela; Silva, Romina; Peixoto, Ana; Rocha, Patrícia; Veiga, Isabel; Santos, Catarina; Santos, Rui; Cabreira, Verónica; Lopes, Paula; Henrique, Rui; Teixeira, Manuel R
Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite-stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Yang, Baiyu; Gapstur, Susan M; Newton, Christina C; Jacobs, Eric J; Campbell, Peter T
Alcohol consumption is associated with a higher risk of colorectal cancer, but to the authors' knowledge its influence on survival after a diagnosis of colorectal cancer is unclear. The authors investigated associations between prediagnosis and postdiagnosis alcohol intake with mortality among survivors of colorectal cancer. The authors identified 2458 men and women who were diagnosed with invasive, nonmetastatic colorectal cancer between 1992 (enrollment into the Cancer Prevention Study II Nutrition Cohort) and 2011. Alcohol consumption was self-reported at baseline and updated in 1997, 1999, 2003, and 2007. Postdiagnosis alcohol data were available for 1599 participants. Of the 2458 participants diagnosed with colorectal cancer, 1156 died during follow-up through 2012. Prediagnosis and postdiagnosis alcohol consumption were not found to be associated with all-cause mortality, except for an association between prediagnosis consumption of colorectal cancer-specific mortality, although there was some suggestion of increased colorectal cancer-specific mortality with postdiagnosis drinking (RR, 1.27 [95% CI, 0.87-1.86] for current drinking of colorectal cancer. The association between postdiagnosis drinking and colorectal cancer-specific mortality should be examined in larger studies of individuals diagnosed with nonmetastatic colorectal cancer. Cancer 2017;123:2006-2013. © 2017 American Cancer Society. © 2017 American Cancer Society.
Full Text Available Background: In the literature there are a number of studies that suggest a possible correlation between cholelithiasis/cholecystectomy and colorectal cancer. The exposure of the colon mucosa to the action of bile acids that potentially have a carcinogenic effect due to the change in anatomy after cholecystectomy, seems to be the explanation of this association. The purpose of this paper was to search for such a correlation in our study group. Methods: We performed a retrospective cross-sectional study, analyzing the patients admitted to the First Surgical Clinic of the County Emergency Clinical Hospital Tîrgu Mureș, between January 1st, 2005 - December 31st, 2010. Analyzing the medical records, operation protocols and histopathological results, we paid attention to demographics, location of neoplasia, the time elapsed since the cholecystectomy to the discovery of neoplasia, histological types, trying to perform correlations between these parameters and the lithiasic factor. Results: Out of the 534 patients admitted and operated with the diagnosis of colorectal cancer, 15.6% (n = 83 showed a history of gallbladder stone affection. Most patients came from urban areas, the average age was 67.2 (range 39-88 years, females were more affected. The most common locations were: the sigmoid colon (26.5%, rectum (36.3% and the most common histological form was moderately differentiated adenocarcinoma. Conclusions: Similar to other studies, our work suggests a slight increase in the incidence of colorectal cancer in patients that underwent a cholecystectomy, without drawing a firm conclusion. We deem it necessary to see if diet changes of the Romanian population affect this relationship
Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7
Qiu, Li; Wang, Dao-Rong; Zhang, Xiang-Yun; Gao, Shan; Li, Xiao-Xia; Sun, Gong-Ping; Lu, Xiao-Bo
To investigate the impacts of perioperative blood transfusion on the immune function and prognosis in colorectal cancer (CC) patients. A retrospective analysis was conducted in 1404 CC patients, including 1223 sporadic colorectal cancer (SCC) patients and 181 hereditary colorectal cancer (HCC) patients. Among them, 701 SCC and 102 HCC patients received perioperative blood transfusion. The amount of T lymphocyte subsets and natural killer (NK) cells was measured. All patients received a 10-year follow-up and relapse, metastasis and curative conditions were recorded. In SCC group, mortality, local recurrence and distant metastasis rate of transfused patients were significantly higher than non-transfused patients (all P transfused patients than non-transfused patients (P = 0.002). SCC patients transfused with ≥3 U of blood had significantly higher mortality than patients transfused with blood transfusion in SCC and HCC patients (all P blood transfusion (P blood transfusion had markedly lower 10-year survival rates as compared with those who did not receive (both P transfused with ≥3 U of blood had remarkably lower survival rates compared with SCC patients transfused with blood transfusion could impact immune function, increased postoperative mortality, local recurrence rate and distant metastasis rate in CC patients; and survival rate of CC patients is negatively related to blood transfusion volume. Copyright © 2016. Published by Elsevier Ltd.
Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant
Hasumi, Hisashi; Yao, Masahiro
Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Symer, Matthew M; Wong, Natalie Z; Abelson, Jonathan S; Milsom, Jeffrey W; Yeo, Heather L
Hormone replacement therapy has been shown to reduce colorectal cancer incidence, but its effect on colorectal cancer mortality is controversial. The objective of this study was to determine the effect of hormone replacement therapy on survival from colorectal cancer. We performed a secondary analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter randomized trial run from 1993 to 2001, with follow-up data recently becoming mature. Participants were women aged 55 to 74 years, without recent colonoscopy. Data from the trial were analyzed to evaluate colorectal cancer incidence, disease-specific mortality, and all-cause mortality based on subjects' use of hormone replacement therapy at the time of randomization: never, current, or former users. A total of 75,587 women with 912 (1.21%) incident colorectal cancers and 239 associated deaths were analyzed, with median follow-up of 11.9 years. Overall, 88.6% were non-Hispanic white, and colorectal cancer incidence in current users compared to never-users was lower (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.94; P = .005), as was death from colorectal cancer (HR, 0.63; 95% CI, 0.47-0.85; P = .002) and all-cause mortality (HR, 0.76; 95% CI, 0.72-0.80; P colorectal cancer incidence and improved colorectal cancer-specific survival, as well as all-cause mortality. Copyright © 2018 Elsevier Inc. All rights reserved.
Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.
Yusoff, Harmy Mohamed; Daud, Norwati; Noor, Norhayati Mohd; Rahim, Amry Abdul
In Malaysia, colorectal cancer is the most common cancer in males and the third most common in females. Mortality due to colorectal cancer can be effectively reduced with early diagnosis. This study was designed to look into colorectal cancer screening participation and its barriers among average risk individuals in Malaysia. A cross sectional study was conducted from August 2009 till April 2010 involving average risk individuals from 44 primary care clinics in West Malaysia. Each individual was asked whether they have performed any of the colorectal cancer screening methods in the past five years. The barrier questions had three domains: patient factors, test factors and health care provider factors. Descriptive analysis was achieved using Statistical Program for Social Sciences (SPSS) version 12.0. A total of 1,905 average risk individuals responded making a response rate of 93.8%. Only 13 (0.7%) respondents had undergone any of the colorectal cancer screening methods in the past five years. The main patient and test factors for not participating were embarrassment (35.2%) and feeling uncomfortable (30.0%), respectively. There were 11.2% of respondents who never received any advice to do screening. The main reason for them to undergo screening was being advised by health care providers (84.6%). The study showed that participation in colorectal cancer screening in Malaysia is extremely low and multiple factors contribute to this situation. Given the importance of the disease, efforts should be made to increase colorectal cancer screening activities in Malaysia.
Huhn, S.; Pardini, Barbara; Naccarati, Alessio; Vodička, Pavel (ed.); Hemminki, K.; Försti, A.
Roč. 27, č. 2 (2012), s. 197-204 ISSN 0267-8357 R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286 Grant - others:EU FP7(XE) HEALTH-F4-2007-200767 Institutional research plan: CEZ:AV0Z50390512 Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012
Stratton, Kelly L; Alanee, Shaheen; Glogowski, Emily A; Schrader, Kasmintan A; Rau-Murthy, Rohini; Klein, Robert; Russo, Paul; Coleman, Jonathan; Offit, Kenneth
To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was 5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data
Rich, Thereasa A.; Liu, Mei; Etzel, Carol J.; Bannon, Sarah A.; Mork, Maureen E.; Ready, Kaylene; Saraiya, Devki S.; Grubbs, Elizabeth G.; Perrier, Nancy D.; Lu, Karen H.; Arun, Banu K.; Woodard, Terri L.; Schover, Leslie R.; Litton, Jennifer K.
Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered. PMID:24072553
Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)
Five studies presented at the 1992 ASCO meeting are analysed. Kligerman's study was designed to determine if pre-treatment with WR-2721 could p rotect normal tissues from the toxicities induced by radiation therapy (in 100 patients with an advanced rectal cancer). This pre-treatment resulted in a 13% reduction of moderate and severe acute toxicity. No WR-2721 patient experienced moderate or severe late toxicities compared to five in the group without pre-treatment. Minski studied the acute toxicity (during treatment and two weeks after) of combined pelvic radiation therapy, 5-FU and leucovorin when delivered pre-operatively (16 patients) versus post-operatively (25 patients) in patients with rectal cancer. The final report of the inter group study of 5-FU plus levamisole as adjuvant therapy for stage C colon cancer was made by Moertel. With a median follow-up time of 5.5 years, the 5-FU plus levamisole treatment has reduced the recurrence rate by 39%, the cancer related death rate by 32% and the overall death rate by 31%. Most of the recurrences occurred during the first two years. There was a decrease in the liver, great omentum, peritoneum and lung metastases, but there was no modification in loco-regional recurrence rate. Welt presented a phase I/II study of radio-immunotherapy with I 131 monoclonal antibody A33 in patients with advanced colorectal carcinoma. Results were characterized by major hematologic toxicity and minor tumor response rate. Heiss undertook a prospective study to evaluate the influence of homologous blood transfusion on recurrence rate after colorectal cancer surgery. Fifty-eight patients receiving autologous blood transfusion were compared with sixty-two patients receiving homologous transfusion. With a median follow-up of 21 months a higher recurrence rate was found in the homologous group (29.4% versus 16.7%)
Murad-Regadas, Sthela Maria; Bezerra, Carla Camila Rocha; Peixoto, Ana Ligia Rocha; Regadas, Francisco Sérgio Pinheiro; Rodrigues, Lusmar Veras; Siebra, José Airton Gonçalves; da Silva Fernandes, Graziela Olivia; Vasconcelos, Rafael Aragão
ABSTRACTObjectives:To assess the prevalence of polyps in patients with a family history of colorectal cancer, in comparison to asymptomatic individuals with indication for screening.Methods:A prospective study in a group of patients who underwent colonoscopy between 2012 and 2014. Patients were divided into two groups: Group I: no family history of colorectal cancer, and Group II: with a family history in ﬁrst-degree relatives. Demographic characteristics, ﬁndings on colonoscopy...
Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian
Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.
The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.
The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.
Full Text Available Integrin is important for cell growth, invasion and metastasis, which are frequently observed in malignant tumors. The periostin (POSTN gene encodes the ligand for integrin, one of the key focal adhesion proteins contributing to the formation of a structural link between the extracellular matrix and integrins. High expression levels of the POSTN gene are correlated with numerous human malignancies. We examined POSTN protein in colorectal cancer specimens from 115 patients by strictly following up using immunohistochemistry. Cytoplasm immunohistochemical staining showed POSTN protein expression in colorectal cancers. The positive expression rate of POSTN protein (59.13%, 68/115 in colorectal cancers was significantly higher than that in adjacent normal colon mucosa (0.47%, 11/109. POSTN over-expression in colorectal cancers was positively correlated with tumor size, differentiation, lymph node metastasis, serosal invasion, clinical stage and five-year survival rates. Further analysis showed that patients with advanced stage colorectal cancer and high POSTN expression levels had lower survival rates than those with early stage colorectal cancer and low POSTN expression levels. Overall, our results showed that POSTN played an important role in the progression of colorectal cancers.
Full Text Available A substantial proportion of colorectal cancers (CRCs are interval CRCs (I-CRCs; i.e., CRCs diagnosed soon after a colonoscopy. Chromosomal instability (CIN is defined as an increase in the rate of which whole chromosomes/large chromosomal fragments are gained or lost and is observed in 85% of non-hereditary CRCs. The contribution of CIN to the etiology of I-CRCs remains unknown. We established a fluorescence in situ hybridization (FISH approach to characterize CIN by enumerating specific chromosomes and determined the prevalence of numerical CIN in a population-based cohort of I-CRCs and control (sporadic CRCs. Using the population-based Manitoba Health administrative databases and Manitoba Cancer Registry, we identified an age, sex, and colonic site of CRC matched cohort of I-CRCs and controls and retrieved their archived paraffin-embedded tumor samples. FISH chromosome enumeration probes specifically recognizing the pericentric regions of chromosomes 8, 11, and 17 were first used on cell lines and then CRC tissue microarrays to detect aneusomy, which was then used to calculate a CIN score (CS. The 15th percentile CS for control CRC was used to define CIN phenotype. Mean CSs were similar in the control CRCs and I-CRCs; 82% of I-CRCs exhibited a CIN phenotype, which was similar to that in the control CRCs. This study suggests that CIN is the most prevalent contributor to genomic instability in I-CRCs. Further studies should evaluate CIN and microsatellite instability (MSI in the same cohort of I-CRCs to corroborate our findings and to further assess concomitant contribution of CIN and MSI to I-CRCs.
Fantini, C; Pedinielli, J-L; Manouvrier, S
Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.
Schmit, Stephanie L; Rennert, Hedy S; Rennert, Gad; Gruber, Stephen B
Coffee contains several bioactive compounds relevant to colon physiology. Although coffee intake is a proposed protective factor for colorectal cancer, current evidence remains inconclusive. We investigated the association between coffee consumption and risk of colorectal cancer in 5,145 cases and 4,097 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study in northern Israel. We also examined this association by type of coffee, by cancer site (colon and rectum), and by ethnic subgroup (Ashkenazi Jews, Sephardi Jews, and Arabs). Coffee data were collected by interview using a validated, semi-quantitative food frequency questionnaire. Coffee consumption was associated with 26% lower odds of developing colorectal cancer [OR (drinkers vs. non-drinkers), 0.74; 95% confidence interval (CI), 0.64-0.86; P consumption alone (OR, 0.82; 95% CI, 0.68-0.99; P = 0.04) and for boiled coffee (OR, 0.82; 95% CI, 0.71-0.94; P = 0.004). Increasing consumption of coffee was associated with lower odds of developing colorectal cancer. Compared with 2.5 servings/day (OR, 0.46; 95% CI, 0.39-0.54; P colorectal cancer (Ptrend cancers. Coffee consumption may be inversely associated with risk of colorectal cancer in a dose-response manner. Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 634-9. ©2016 AACR. ©2016 American Association for Cancer Research.
Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.
Van Blarigan, Erin L; Meyerhardt, Jeffrey A
This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. © 2015 by American Society of Clinical Oncology.
Ambalam, Padma; Raman, Maya; Purama, Ravi Kiran; Doble, Mukesh
Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.
Geirdal, Amy Østertun; Reichelt, Jon G; Dahl, Alv A; Heimdal, Ketil; Maehle, Lovise; Stormorken, Astrid; Møller, Pål
To examine psychological distress in women at risk of familial breast-ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC) with absence of demonstrated mutations in the family (unknown mutation). Two-hundred and fifty three consecutive women at risk of FBOC and 77 at risk of HNPCC and with no present or past history of cancer. They were aware of their risk and had received genetic counseling. Comparisons were made between these two groups, normal controls, and women who were identified to be BRCA1 mutation carriers. The questionnaires Beck Hopelessness Scale (BHS), General Health Questionnaire (GHQ-28), Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale (IES) were employed to assess psychological distress. No significant differences concerning psychological distress were observed between women with FBOC and women with HNPCC. Compared to mutation carriers for BRCA1, the level of anxiety and depression was significantly higher in the FBOC group with absence of demonstrated mutation. Compared to normal controls, the level of anxiety was higher, while the level of depression was lower in the groups with unknown mutation. Women in the absence of demonstrated mutations have higher anxiety and depression levels than women with known mutation-carrier status. Access to genetic testing may be of psychologically benefit to women at risk for FBOC or HNPCC.
Bressler Hernandez, Norlan; Martinez Perez, Elliot; Fernandez Rodriguez, Leopoldo; Torres Core, Ramiro
In the current age of minimally invasive surgery, laparoscopic surgery for colon cancer has been established as oncologically equivalent to conventional open surgery. The advantages of laparoscopic surgery have translated into smaller incisions and shorter recovery. Since the advent of laparoscopy, surgeons have been fueled to develop less invasive operative methods as feasible alternatives to traditional procedures. As techniques evolved and technology advanced, laparoscopy became more widely accepted and is now more commonly used in many institutions. Recently, a trend toward less invasive surgery, driven by patient and surgeon alike, has been a major objective for many institutions because of the ability of laparoscopic surgery to reduce postoperative pain, achieve a quicker recovery time, and improve cosmetic outcomes. Although still evolving, traditional laparoscopy has served as a foundation for even further refinements in the minimally invasive approach and as a result, more advanced equipment and newer techniques have arisen
Jin, Hei-Ying; Zhao, Ronghua; Liu, Xiufang; Li, Vicky Ka Ming; Ding, Yijiang; Yang, Bolin; Geng, Jianxiang; Lai, Rensheng; Ding, Shuqing; Ni, Min
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer. In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes. Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH
Grasso, Catherine S; Giannakis, Marios; Wells, Daniel K; Hamada, Tsuyoshi; Mu, Xinmeng Jasmine; Quist, Michael; Nowak, Jonathan A; Nishihara, Reiko; Qian, Zhi Rong; Inamura, Kentaro; Morikawa, Teppei; Nosho, Katsuhiko; Abril-Rodriguez, Gabriel; Connolly, Charles; Escuin-Ordinas, Helena; Geybels, Milan S; Grady, William M; Hsu, Li; Hu-Lieskovan, Siwen; Huyghe, Jeroen R; Kim, Yeon Joo; Krystofinski, Paige; Leiserson, Mark D M; Montoya, Dennis J; Nadel, Brian B; Pellegrini, Matteo; Pritchard, Colin C; Puig-Saus, Cristina; Quist, Elleanor H; Raphael, Ben J; Salipante, Stephen J; Shin, Daniel Sanghoon; Shinbrot, Eve; Shirts, Brian; Shukla, Sachet; Stanford, Janet L; Sun, Wei; Tsoi, Jennifer; Upfill-Brown, Alexander; Wheeler, David A; Wu, Catherine J; Yu, Ming; Zaidi, Syed H; Zaretsky, Jesse M; Gabriel, Stacey B; Lander, Eric S; Garraway, Levi A; Hudson, Thomas J; Fuchs, Charles S; Ribas, Antoni; Ogino, Shuji; Peters, Ulrike
To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663 . ©2018 American Association for Cancer Research.
textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These
Purpose: To investigate anticancer effects of bergenin on human colorectal cancer cell lines. Methods: Human colorectal adenocarcinoma cell line HCT116 was treated with various concentrations of bergenin for 24 and 48 h. Cell viability, apoptosis, cell cycle arrest and reactive oxygen species (ROS) level were analyzed ...
van Spaendonck-Zwarts, Karin Y.; Badeloe, Sadhanna; Oosting, Sjoukje F.; Hovenga, Sjoerd; Semmelink, Harry J. F.; van Moorselaar, R. Jeroen A.; van Waesberghe, Jan Hein; Mensenkamp, Arjen R.; Menko, Fred H.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation
Dziki, Łukasz; Puła, Anna; Stawiski, Konrad; Mudza, Barbara; Włodarczyk, Marcin; Dziki, Adam
The aim of the study was to assess patients' awareness of the prevention and treatment of colorectal cancer. Patients diagnosed with colorectal cancer, hospitalised at the Department of General and Colorectal Surgery of the Medical University in Łódź during the period from January 2015 to April 2015, were asked to complete a questionnaire concerning their families' medical case record, factors predisposing them to the development of colorectal cancer, the tests applied in diagnostics, and the treatment process. The questionnaire comprised 42 closed-ended questions with one correct answer. A statistical analysis of all answers was carried out. The study group consisted of 30 men and 20 women aged 27-94 years old. A strong, statistically significant negative correlation between a patient's age and his/her awareness of the prevention and treatment of colorectal cancer was noted (pcancer (p=0.008), and the awareness of the prevention programme. The women's group was characterised by statistically significantly greater awareness of colonoscopy as a screening examination (p=0.004). Patients need more information on colorectal cancer, its risk factors, prevention, the treatment process, and postoperative care. Lack of awareness of the colorectal cancer issue can be one of the major factors contributing to the high incidence of this disease.
Kavitha P Raj
Full Text Available Background: Patients with history of colorectal cancer (CRC are at increased risk for developing a second primary colorectal cancer (SPCRC as compared to the general population. However, the degree of risk is uncertain. Here, we attempt to quantify the risk, using data from the large population-based California Cancer Registry (CCR. Materials and Methods: We analyzed the CCR data for cases with surgically-treated colon and rectal cancer diagnosed during the period 1990-2005 and followed through up to January 2008. We excluded those patients diagnosed with metastatic disease and those in whom SPCRC was diagnosed within 6 months of the diagnosis of the primary CRC. Standardized incidence ratios (SIR with 95% confidence intervals (CI were calculated to evaluate risk as compared to the underlying population after taking into account age, sex, ethnicity, and time at risk. Results: The study cohort consisted of 69809 cases with colon cancer and 34448 with rectal cancer. Among these patients there were 1443 cases of SPCRCs. The SIR for developing SPCRC was higher in colon cancer survivors (SIR=1.4; 95% CI: 1.3 to 1.5 as compared to the underlying population. The incidence of SPCRC was also higher in females (SIR=1.5; 95% CI: 1.3 to 1.6 and Hispanics (SIR=2.0; 95% CI: 1.7 to 2.4 with primary colon cancer. The SIR for developing an SPCRC was higher only among those whose initial tumor was located in the descending colon (SIR=1.6; 95% CI: 1.3 to 2.0 and proximal colon (SIR=1.4; 95% CI: 1.3 to 1.6. Conclusions: Our results confirm that CRC patients, especially females and Hispanics, are at a higher risk of developing SPCRC than the general population. Differential SPCRC risk by colorectal tumor subsite is dependent on gender and ethnicity, underscoring the heterogeneous nature of CRC.
Nygård, Sune Boris; Christensen, Ib Jarle; Smith, David Hersi
Abstract Objective. We propose a repurposing strategy where anthracyclines are reintroduced to a subgroup of patients with metastatic colorectal cancer with the highest likelihood of response. In breast cancer, DNA topoisomerase II alpha gene (TOP2A) alterations predict incremental benefit...... of anthracyclines, but this association has not been investigated in colorectal cancer. Frequency analysis of TOP2A gene alterations in colorectal cancer and the association with prognosis are evaluated and the challenges of using a TOP2A/CEN-17 FISH probe combination are addressed. Material and methods. Formalin......-fixed, paraffin-embedded material from 154 stage III colorectal cancer patients included in the RANX05 clinical trial was retrospectively assessed for TOP2A gene alterations using FISH. The TOP2A/CEN-17 ratio as well as the TOP2A gene copy number alone was used to define gene alterations and associations between...
Li, Junyan; Jing, Ruilin; Wei, Hongyi; Wang, Minghao; Qi, Xiaowei; Liu, Haoxi; Liu, Jian; Ou, Jianghua; Jiang, Weihua; Tian, Fuguo; Sheng, Yuan; Li, Hengyu; Xu, Hong; Zhang, Ruishan; Guan, Aihua; Liu, Ke; Jiang, Hongchuan; Ren, Yu; He, Jianjun; Huang, Weiwei; Liao, Ning; Cai, Xiangjun; Ming, Jia; Ling, Rui; Xu, Yan; Hu, Chunyan; Zhang, Jianguo; Guo, Baoliang; Ouyang, Lizhi; Shuai, Ping; Liu, Zhenzhen; Zhong, Ling; Zeng, Zhen; Zhang, Ting; Xuan, Zhaoling; Tan, Xuanni; Liang, Junbin; Pan, Qinwen; Chen, Li; Zhang, Fan; Fan, Linjun; Zhang, Yi; Yang, Xinhua; Li, Jingbo; Chen, Chongjian; Jiang, Jun
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n=937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n=18), PALB2 (n=11), CHEK2 (n=6), ATM (n=6), and BARD1 (n=5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes. This article is protected by copyright. All rights reserved. © 2018 UICC.
Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.
Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy
Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.
Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...
Venäläinen, Markus K; Roine, Antti N; Häkkinen, Merja R; Vepsäläinen, Jouko J; Kumpulainen, Pekka S; Kiviniemi, Mikko S; Lehtimäki, Terho; Oksala, Niku K; Rantanen, Tuomo K
The declining mortality rate of patients with colorectal cancer (CRC) can be explained, at least partially, with early diagnosis. Simple diagnostic methods are needed to achieve a maximal patient participation rate in screening. Liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) was used to determine urinary polyamine (PA) profiles. In a prospective setting, 116 patients were included in the study: 57 with CRC, 13 with inflammatory bowel disease (IBD), 12 with adenoma, and 34 controls. N1,N12-diacetylspermine (DiAcSPM) level was significantly higher in patients with CRC than controls (sensitivity=78.0%, specificity=70.6%; p=0.00049). The level of diacetylated cadaverine (p=0.0068) was lower and that of diacetylated putrescine (p=0.0078) was higher in patients with CRC than in those with IBD. Cadaverine (p=0.00010) and spermine (p=0.042) levels were lower and that of DiAcSPM (p=0.018) higher in patients with CRC than in those with adenoma. The simultaneous determination of urinary PAs by means of LC-MS/MS can be used to discriminate CRC from controls and patients with benign colorectal diseases. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Julian R Marchesi
Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.
Full Text Available It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP," characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI. We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations.
Siraj, Abdul K; Prabhakaran, Sarita; Bavi, Prashant; Bu, Rong; Beg, Shaham; Hazmi, Mohsen Al; Al-Rasheed, Maha; Al-Assiri, Mohammed; Sairafi, Rami; Al-Dayel, Fouad; Al-Sanea, Nasser; Uddin, Shahab; Al-Kuraya, Khawla S
Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS. A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines. Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations. The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. © 2015 American Cancer Society.
Kamran Moshfeghi; Abolfazl Mohammad-Beigi; Davood Hamedi-Sanani; Masoud Bahrami
Background: Colorectal cancer is one of the most common cancers worldwide including 38% of gastrointestinal cancers. Colorectal cancer is the third type of Iranian men and fourth in women in ranking. The purpose of this study was to determine the role of environmental risk factors in colorectal cancer.Materials and Method: In this case-control study, the authors selected cases from colorectal cancer patients in Arak and controls were selected from Arak hospitals in proportion to the number of...
Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.
Murayama, Hiroki; Watanabe, Tadashi; Tadokoro, Masanori; Takagi, Hiroshi; Sakuma, Sadayuki; Sakamoto, Junichi.
Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with clorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125 I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131 I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with γ-camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer. (author)
Hanne Meijers Heijboer
Full Text Available Abstract Hereditary cancer refers to cancers caused by germline mutations in cancer predisposing genes. These mutations confer a significantly increased risk of cancer, are rare, and are in the majority of cases autosomal dominantly inherited. Since the eighties of last century more than 115 cancer predisposing genes have been identified. In many Western countries genetic testing of patients and families with clustering of cancers started early, and was often performed by clinical geneticists (MDs performed the counselling and pedigree analyses and by molecular biologists (in laboratories within departments of clinical genetics. It turned out to be a long path to fully realize the promise of cancer predisposing genes. The clinical utility of many cancer genetic tests and subsequent risk reducing interventions has not yet been validated and pitfalls in e.g. misinterpretation of genetic variants showed up. However, without doubt genetic testing for mutations will eventually turn out as a strong tool to save lives from early cancer death and will become part of standard cancer care throughout the developed world. Apart from primary surgical prevention, major progress is to be expected in earlier diagnoses, tailored therapies, and possibly chemoprevention. Ideally researchers, clinical geneticists, molecular biologists, surgeons, oncologists, gynaecologists and other professionals will work together to reach this goal. Keywords : clinical genetics, germline, hereditary cancers, cancer predisposing genes
Donovan, Micah G; Selmin, Ornella I; Doetschman, Tom C; Romagnolo, Donato F
Colorectal cancer (CRC) is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma-carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD) is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern.
Donovan, Micah G.; Selmin, Ornella I.; Doetschman, Tom C.; Romagnolo, Donato F.
Colorectal cancer (CRC) is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma–carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD) is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern. PMID:29259973
Micah G. Donovan
Full Text Available Colorectal cancer (CRC is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma–carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern.
Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.
Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117
Sun, Q; Ding, Y; Zhang, J
To study the methodology and significance of flow cytometry in detecting lymph node micrometastasis of colorectal cancer. One hundred sixty-two cellular suspensions were prepared with lymph nodes which were resected radically on 25 patients with colorectal cancer and in which no cancer cells were found by HE staining. Different concentrations of cultured Lovo colorectal cancer cells were added into the celular suspension prepared from lymph node tissue of persons without colorectal cancer in order to prepare a control model. Dual staining with CK/FTTC and PI was made to the sedimetns from those 2 kinds of suspension. Flow cytometry was used to detect cancer cells. An ideal correlation was obtained between the detection value and the theoretical value of cancer cells in the specimen suspensions and control models (r = 0.097 6) with a sensitivity rate of 10/10(5). Cancer cells were detected from 7 out of the 25 patients and 30 of the 162 cellular suspensions. The detection rate was correlated with the size and infiltrating depth of the cancer. Flow cytometry is a reliable, rapid, and quantitative method for detecting lymph node micrometastasis in colorectal cancer.
Fung, Teresa T; Brown, Lisa S
Diet and lifestyle play a significant role in the development of colorectal cancer, but the full complexity of the association is not yet understood. Dietary pattern analysis is an important new technique that may help to elucidate the relationship. This review examines the most common techniques for extrapolating dietary patterns and reviews dietary pattern/colorectal cancer studies published between September 2011 and August 2012. The studies reviewed are consistent with prior research but include a more diverse international population. Results from investigations using a priori dietary patterns (i.e., diet quality scores) and a posteriori methods, which identify existing eating patterns (i.e., principal component analysis), continue to support the benefits of a plant-based diet with some dairy as a means to lower the risk of colorectal cancer, whereas a diet high in meats, refined grains, and added sugar appears to increase risk. The association between colorectal cancer and alcohol remains unclear.
Roelands, Jessica; Kuppen, Peter J. K.; Vermeulen, Louis; Maccalli, Cristina; Decock, Julie; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide; Hendrickx, Wouter
The immune system has a substantial effect on colorectal cancer (CRC) progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies) is influenced by the immune system. The molecular characterization of
Puppa, Giacomo; Poston, Graeme; Jess, Per
lesions encountered, in particular, during radiological staging of patients with colorectal cancer. In this article the diagnosis of these lesions with multiple imaging modalities, their frequency, significance and relevance to staging and disease management are described in a multidisciplinary way...
Colorectal cancer (CRC) prevention strategies include avoiding known risk factors, adopting a healthy lifestyle, polyp removal, and aspirin. Get detailed information about risk factors for CRC and potential interventions for prevention in this summary for clinicians.
There are five types of tests that are used to screen for colorectal cancer: fecal occult blood test, sigmoidoscopy, colonoscopy, virtual colonoscopy, and DNA stool test. Learn more about these and other tests in this expert-reviewed summary.
Johansen, Julia Sidenius; Christensen, Ib Jarle; Jørgensen, Lars Nannestad
The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred.......05-1.40; P = 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P = 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful...
Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario
The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.
Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.
Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to
Tol, Jolien; Koopman, Miriam; Cats, Annemieke; Rodenburg, Cees J.; Creemers, Geert J. M.; Schrama, Jolanda G.; Erdkamp, Frans L. G.; Vos, Allert H.; van Groeningen, Cees J.; Sinnige, Harm A. M.; Richel, Dirk J.; Voest, Emile E.; Dijkstra, Jeroen R.; Vink-Börger, Marianne E.; Antonini, Ninja F.; Mol, Linda; van Krieken, Johan H. J. M.; Dalesio, Otilia; Punt, Cornelis J. A.
Background Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor ( VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor ( EGFR) antibody cetuximab
Fung, Teresa T.; Brown, Lisa S.
Diet and lifestyle play a significant role in the development of colorectal cancer, but the full complexity of the association is not yet understood. Dietary pattern analysis is an important new technique that may help to elucidate the relationship. This review examines the most common techniques for extrapolating dietary patterns and reviews dietary pattern/colorectal cancer studies published between September 2011 and August 2012. The studies reviewed are consistent with prior research but ...
Rafaelsen, Søren Rafael; Kronborg, Ole; Fenger, Claus
PURPOSE: This study was designed to compare diagnostic accuracies of measuring liver enzymes, preoperative ultrasonography, surgical examination, and intraoperative ultrasonography for detection of liver metastases from colorectal cancer. METHODS: Blind, prospective comparisons of diagnostic...... examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations, and results were unknown to the other experienced ultrasonologist who performed the intraoperative examinations. The latter, also was unaware...
This 60 second public service announcement is based on the November 2013 CDC Vital Signs report. Colorectal cancer screening saves lives, but only if you get tested. If youâre between 50 and 75, talk with your doctor about which test is best for you. If you have inflammatory bowel disease or a family history of colorectal cancer or polyps, ask your doctor if you should start screening before age 50.
Takiyama, Aki; Tanaka, Toshiaki; Yamamoto, Yoko; Hata, Keisuke; Ishihara, Soichiro; Nozawa, Hiroaki; Kawai, Kazushige; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Watanabe, Toshiaki
Few studies have evaluated the risk of postoperative colorectal neoplasms stratified by the nature of primary colorectal cancer (CRC). In this study, we revealed it on the basis of the microsatellite (MS) status of primary CRC. We retrospectively reviewed 338 patients with CRC and calculated the risk of neoplasms during postoperative surveillance colonoscopy in association with the MS status of primary CRC. A propensity score method was applied. We identified a higher incidence of metachronous rectal neoplasms after the resection of MS stable CRC than MS instable CRC (adjusted HR 5.74, p=0.04). We also observed a higher incidence of colorectal tubular adenoma in patients with MSS CRC (adjusted hazard ratio 7.09, pcolorectal cancer influenced the risk of postoperative colorectal neoplasms. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei; Kuasne, Hellen; Spencer, Ranyell Matheus; Nakagawa, Wilson Toshihiko; Bezerra, Tiago Santoro; Kupper, Bruna Catin; Takahashi, Renata Maymi; Barros Filho, Mateus; Rogatto, Silvia Regina; Lopes, Ademar
Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002). These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.
Lee, Chun Seng
Colorectal cancer (CRC) screening has been shown to be effective in reducing CRC incidence and mortality. There are currently a number of screening modalities available for implementation into a population-based CRC screening program. Each screening method offers different strengths but also possesses its own limitations as a population-based screening strategy. We review the current evidence base for accepted CRC screening tools and evaluate their merits alongside their challenges in fulfilling their role in the detection of CRC. We also aim to provide an outlook on the demands of a low-risk population-based CRC screening program with a view to providing insight as to which modality would best suit current and future needs.
Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H
BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival...... population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours......, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy. CONCLUSIONS: Adding cetuximab to Nordic FLOX did not provide any clinical...
Groessl, E. J.; Allison, M. A.; Ho, S. B.; Groessl, E. J.; Allison, M. A.; Ho, S. B.; Larson, J. C.; Snetslaar, L. G.; Lane, D. S.; Tharp, K. M.; Stefanick, M. L.
Higher coffee consumption has been associated with decreased incidence of colorectal cancer. Our objective was to examine the relationship of coffee intake to colorectal cancer incidence in a large observational cohort of postmenopausal US women. Methods. Data were collected for the Women’s Health Initiative Observational Study providing a follow-up period of 12.9 years. The mean age of our sample ( N = 83,778 women) was 63.5 years. Daily coffee intake was grouped into 3 categories: None, moderate (>0-<4 cups), and high (4+ cups). Proportional hazards modeling was used to evaluate the relationship between coffee intake and colorectal cancer. Results. There were 1,282 (1.53%) new cases of colorectal cancer during follow-up. Compared to nondrinkers, moderate and high coffee drinkers had an increased incidence of colorectal cancer in multivariate analysis (HR 1.15, 1.02-1.29; HR 1.14, 0.93-1.38). Moderate drip brew coffee intake (HR 1.20, 1.05-1.36) and high non drip brew coffee intake (HR 1.43, 1.01-2.02) were associated with increased odds. Conclusion. Our results suggesting increased incidence of colorectal cancer associated with higher coffee consumption contradict recent meta-analyses but agree with a number of other studies showing that coffee increases risk or has no effect. Brew method results are novel and warrant further research.
Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon
To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.
Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan
Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differe...
Sanford, Stacy D; Zhao, Fengmin; Salsman, John M; Chang, Victor T; Wagner, Lynne I; Fisch, Michael J
Cancer incidence has increased among young adults (YAs) and survival rates have not improved compared with other age groups. Patient-reported outcomes may enhance our understanding of this vulnerable population. In a multisite prospective study, patients completed a cancer symptom inventory at the time of enrollment (T1) and 4 weeks to 5 weeks later (T2). YAs (those aged ≤ 39 years) with breast or colorectal cancer were compared with older adults (those aged ≥ 40 years) with breast or colorectal cancer with regard to symptom severity, symptom interference, changes over time, and medical care. Participants included 1544 patients with breast cancer (96 of whom were YAs) and 718 patients with colorectal cancer (37 of whom were YAs). Compared with older adults, YAs with breast cancer were more likely to report moderate/severe drowsiness, hair loss, and symptom interference with relationships at T1. YAs with colorectal cancer were more likely to report moderate/severe pain, fatigue, nausea, distress, drowsiness, shortness of breath, and rash plus interference in general activity, mood, work, relationships, and life enjoyment compared with older adults. Compared with older adults, shortness of breath, appetite, and sore mouth were more likely to improve in YAs with breast cancer; vomiting was less likely to improve in YAs with colorectal cancer. Referrals for supportive care were few, especially among patients with colorectal cancer. YAs with breast cancer were somewhat more likely to be referred to nutrition and psychiatry services than older patients. YAs reported symptom severity, symptom interference, and variations over time that were distinct from older patients. Distinctions were found to differ by diagnostic group. These findings enhance the understanding of symptom burden in YAs and inform the development of targeted interventions and future research. © 2014 American Cancer Society.
Sailaja Suryadevara, , , ,
Full Text Available Introduction: Colorectal cancers are a common disease of oncological practice. A raising incidence is seen in Asian population. It is one of the cancers where screening and early diagnosis are possible. Very few articles are there about the cancer scenario in India. A study of the disease profile helps in screening, early diagnosis and management of the disease in developing countries. Aim: To study the cancer presentation in our population which can help in developing strategies for better control of disease. Material and Methods: Medical records of 171 patients registered at Kidwai Hospital from 2010 to 2012 were retrospectively reviewed. Data including age at presentation, sex, location of the cancer and stage at presentation were analyzed. Results: The male to female ratio was 1.26:1 in rectal cancer. In colon cancer the ratio was 1:1.3. The mean age at presentation was 47 years in males and 51 years in females in colorectal cancers together. Thirty eight percent of the patients were less than 45 years old. Eighty percent of the cases were rectal cancers. In 71% of rectal cancers the growth was located within 5cm from anal verge (AV. Stage III was the commonest stage of presentation. Abdominoperineal resection (APR was the commonest surgical procedure done. Inoperability was highest with lower rectal cancer. Conclusion: Younger age at presentation, low lying rectal cancers and advanced stage at presentation were observed in our study group which includes predominantly rural population. Rectal cancers are the most common cancers referred among colorectal cancers. Screening for colorectal cancers and early evaluation of symptomatic cases need to be encouraged. Patients should be educated regarding this. Screening strategies, etiopathogenesis and genetic abnormalities in colorectal cancer patients need to be defined in developing countries.
Kershaw, Sophie K.; Byrne, Helen M.; Gavaghan, David J.; Osborne, James M.
Colorectal cancer (CRC) has formed a canonical example of tumourigenesis ever since its use in Fearon and Vogelstein's linear model of genetic mutation, and continues to generate a huge amount of research interest. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical and computational modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the 'Hallmarks of Cancer' has been extended in recent times and provides an excellent basis for future research. The authors present a timely summary of the literature relating to CRC, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. The authors conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that theoretical modelling can provide. © The institution of engineering and technology 2013.
Kershaw, Sophie K.
Colorectal cancer (CRC) has formed a canonical example of tumourigenesis ever since its use in Fearon and Vogelstein\\'s linear model of genetic mutation, and continues to generate a huge amount of research interest. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical and computational modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the \\'Hallmarks of Cancer\\' has been extended in recent times and provides an excellent basis for future research. The authors present a timely summary of the literature relating to CRC, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. The authors conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that theoretical modelling can provide. © The institution of engineering and technology 2013.
Colorectal cancer is one of the most common cancers in Europe and in North America. Cornerstone of the treatment of localized colorectal cancer is surgical resection followed by chemotherapy or radio-chemotherapy in indicated cases. For patients with Stage III colon cancer recent data have shown efficacy through the combining fluorouracil-based chemotherapy with oxaliplatin into adjuvant treatment program. For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at high risk for disease recurrence. Current randomized clinical trials in the adjuvant therapy of colorectal cancer are examining the value of adding agents known to be active in metastatic disease, including those that modify specific molecular targets. (author)
... a week-long series to promote colon and rectal (colorectal) cancer awareness and screening. Following that, research showed that ... niddk.nih.gov The American Cancer Society: www.cancer.org The American Society of Colon & Rectal Surgeons: www.fascrs.org Spring 2009 Issue: Volume ...
Liu, L.; Lemmens, V.E.; de Hingh, I.H.J.T.; de Vries, E.; Roukema, J.A.; van Leerdam, M.E.; Coebergh, J.W.; Soerjomataram, I.
Background: Compared with the general population, patients with a previous colorectal cancer are at higher risk for a second colorectal cancer, but detailed risk analysis by subsite is scarce. Objective: Our goal was to investigate the risk of a second cancer in relation to subsite as a basis for
In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504
Colorectal cancer is the third leading cause of cancer-related death in males and females in developed countries. Metastases in distant organs, which develop in 50% of colorectal cancer patients, are responsible for the majority of colorectal cancer deaths. Treatment of metastatic disease should
Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Àlex; Medina-Hayas, Manuel
Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy
van Dooren, S.; Rijnsburger, A. J.; Seynaeve, C.; Kriege, A.; Duivenvoorden, H. J.; Bartels, C. C. M.; Essink-Bot, M. L.; de Koning, H. J.; Tibben, A.
BACKGROUND: The Magnetic Resonance Imaging Screening study evaluates the efficacy and psychological impact of a surveillance program for women at increased risk for hereditary or familial breast cancer in the Netherlands. Surveillance consists of biannual physical examination, annual mammography,
Meinel, F.G.; Schramm, N.; Graser, A.; Reiser, M.F.; Rist, C.; Haug, A.R.
Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has emerged as a very useful imaging modality in the management of colorectal carcinoma. Data from the literature regarding the role of PET/CT in the initial diagnosis, staging, radiotherapy planning, response monitoring and surveillance of colorectal carcinoma is presented. Future directions and economic aspects are discussed. Computed tomography (CT), magnetic resonance imaging (MRI) and FDG-PET for colorectal cancer and endorectal ultrasound for rectal cancer. Combined FDG-PET/CT. While other imaging modalities allow superior visualization of the extent and invasion depth of the primary tumor, PET/CT is most sensitive for the detection of distant metastases of colorectal cancer. We recommend a targeted use of PET/CT in cases of unclear M staging, prior to metastasectomy and in suspected cases of residual or recurrent colorectal carcinoma with equivocal conventional imaging. The role of PET/CT in radiotherapy planning and response monitoring needs to be determined. Currently there is no evidence to support the routine use of PET/CT for colorectal screening, staging or surveillance. To optimally exploit the synergy between morphologic and functional information, FDG-PET should generally be performed as an integrated FDG-PET/CT with a contrast-enhanced CT component in colorectal carcinoma. (orig.) [de
Orlich, Michael J; Singh, Pramil N; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F; Beeson, W Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L; Herring, R Patti; Fraser, Gary E
Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96,354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77,659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81 (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals. Vegetarian diets are
Orlich, Michael J.; Singh, Pramil N.; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F.; Beeson, W. Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L.; Herring, R. Patti; Fraser, Gary E.
IMPORTANCE Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77 659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64–0.95) for all colorectal cancers, 0.81 (95%CI, 0.65–1.00) for colon cancer, and 0.71 (95% CI, 0.47–1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59–1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65–1.02); in pescovegetarians, 0.57 (95% CI, 0.40–0.82); and in semivegetarians, 0.92 (95% CI, 0.62–1.37) compared with
This 60 second Public Service Announcement (PSA) is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer. Created: 7/5/2011 by Centers for Disease Control and Prevention (CDC). Date Released: 7/5/2011.
Feng, Yu-Liang; Shu, Long; Zheng, Pei-Fen; Zhang, Xiao-Yan; Si, Cai-Juan; Yu, Xiao-Long; Gao, Wei; Zhang, Lun
The analysis of dietary patterns has recently drawn considerable attention as a method of investigating the association between the overall whole diet and the risk of colorectal cancer. However, the results have yielded conflicting findings. Here, we carried out a meta-analysis to identify the association between dietary patterns and the risk of colorectal cancer. A total of 40 studies fulfilled the inclusion criteria and were included in this meta-analysis. The highest category of 'healthy' dietary pattern compared with the lowest category was apparently associated with a decreased risk for colorectal cancer [odds ratio (OR)=0.75; confidence interval (CI): 0.68-0.83; Pcolorectal cancer was shown for the highest compared with the lowest category of a 'western-style' dietary pattern (OR=1.40; CI: 1.26-1.56; Pcolorectal cancer in the highest compared with the lowest category of 'alcohol-consumption' pattern (OR=1.44; CI: 1.13-1.82; P=0.003). The results of this meta-analysis indicate that a 'healthy' dietary pattern may decrease the risk of colorectal cancer, whereas 'western-style' and 'alcohol-consumption' patterns may increase the risk of colorectal cancer.
Chen, Yuetong; Wu, Yuan; Du, Mulong; Chu, Haiyan; Zhu, Lingjun; Tong, Na; Zhang, Zhengdong; Wang, Meilin; Gu, Dongying; Chen, Jinfei
It is well known that the tea extracts, mainly polyphenols as chemo-preventive elements, could act as cancer progression blockers. Although the association between tea consumption and colorectal cancer risk has been widely investigated, the results still remain inconsistent. We conducted a dose-response meta-analysis to evaluate their relationships by enrolling qualified 29 literatures. The summary odds ratio (OR) of colorectal cancer for the highest vs. lowest tea consumption was 0.93 with 0.87-1.00 of 95% confidence intervals (CIs) among all studies with modest heterogeneity (P = 0.001, I2 = 43.4%). Stratified analysis revealed that tea, especially green tea, had a protective effect among female and rectal cancer patients. Particularly, the dose-response analysis showed that there was a significant inverse association between an increment of 1 cup/day of tea consumption and colorectal cancer risk in the subgroup of the green tea drinking (OR = 0.98, 95% CI = 0.96-1.01, Pnonlinear = 0.003) and female (OR = 0.68, 95% CI = 0.56-0.81, Pnonlinear colorectal cancer risk, which may have significant public health implications in the prevention of colorectal cancer and further similar researches.
Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah
This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal
Thorne, Amanda L; Mercer, Stuart J; Harris, Guy JC; Simson, Jay NL
INTRODUCTION An audit of patients presenting with colorectal cancer to our district general hospital during a 2-year period from November 1994 found that 12.1% of cases were diagnosed later than 6 months after initial presentation to a physician. This audit was repeated for a 2-year period from December 2001, to determine whether the introduction of a specialist coloproctology surgery service had led to a reduction in late diagnosis of colorectal cancer. PATIENTS AND METHODS Case notes were reviewed of all patients presenting with colorectal cancer between December 2001 and November 2003. Late diagnosis was defined as diagnosis of colorectal cancer more than 6 months after their first attendance to either their general practitioner or district general hospital. The results were compared with those of the previous study. RESULTS Of a total of 218 patients presenting with colorectal cancer during the study period, 14 (6.4%; 10 men and 4 women) satisfied the criteria for late diagnosis, with the longest delay being 12.5 months. Reasons for late diagnosis were false-negative reporting of barium studies (n = 3), inaccurate tumour biopsy (n = 2), concurrent pathology causing anaemia (n = 4), inappropriate delay in definitive investigation (n = 3), and refusal of investigation by patients (n = 2). CONCLUSIONS There has been a reduction of nearly 50% (12.1% to 6.4%) in the proportion of patients with a late diagnosis of colorectal cancer compared with our previous audit. It is suggested that an important factor in this improvement in diagnosis has been the introduction of a specialist coloproctology surgery service. PMID:17059718
Full Text Available To explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients.
Jansman, FGA; Sleijfer, DT; Coenen, JLLM; De Graaf, JC; Brouwers, JRBJ
Antitumour therapy in advanced colorectal cancer has limited efficacy. For decades, fluorouracil has been the main anticancer drug for the treatment of colorectal cancer. Recently, however, new agents have been introduced: raltitrexed, irinotecan and oxaliplatin. Currently, the dosage for an
Conclusions: Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.
Full Text Available Abstract Background Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs are associated with colorectal cancer risk. Methods A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A, using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter. Results The -537A allele (-537G/A or A/A was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025, while the -158A allele (-158G/A or A/A was involved in protection against colorectal cancer (OR = 0.539, p = 0.032. Haplotype 2 (-537A, -277T, -158G was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021, while haplotype 4 (-537G, -277C, -158A protected against colorectal cancer (OR = 0.539, p = 0.032. EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart. Conclusion Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.
Kavuri, Shyam M; Jain, Naveen; Galimi, Francesco; Cottino, Francesca; Leto, Simonetta M; Migliardi, Giorgia; Searleman, Adam C; Shen, Wei; Monsey, John; Trusolino, Livio; Jacobs, Samuel A; Bertotti, Andrea; Bose, Ron
The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutants are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors neratinib and afatinib. HER2 gene sequencing of 48 cetuximab-resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) wild-type (WT) colorectal cancer patient-derived xenografts (PDX) identified 4 PDXs with HER2 mutations. HER2-targeted therapies were tested on two PDXs. Treatment with a single HER2-targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2-targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2-mutated PDXs. HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer. ©2015 American Association for Cancer Research.
Sherri G. Homan
Full Text Available Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups’ questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02 and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003. The most cited barrier was the complexity of preparation for colonoscopy.
Yardley, C.; Glover, C.; Allen-Mersh, T. G.
Greater public awareness of colorectal cancer symptoms might result in earlier presentation with improved cure by available treatments, but little is known about the extent of public knowledge of colorectal cancer symptoms. We asked a sample of the general population about knowledge of colorectal cancer symptoms and assessed demographic characteristics associated with differences in knowledge. A population-based telephone enquiry into knowledge of colorectal cancer-associated symptoms was con...
Full Text Available INTRODUCTION Colorectal cancer is the third most common cancer which can be detected early by implementation of cancer screening. This has led to decline in colorectal cancer related morbidity and mortality in elderly patients. However, there is increase in the incidence of this cancer in young individuals. This study was undertaken to study the characteristics of young colorectal cancer patients. METHODS AND MATERIALS The study was conducted from 2014 to 2016. All colorectal cancer patients attending the Department of Oncology, who were less than or equal to 50 years of age were included. Patients’ demographic data as well as data regarding the colorectal cancer was collected. The data was entered into MS Excel worksheet and analysed using descriptive statistics. RESULTS This study included 28 patients with a median age of 40 years and equal sex distribution. History of smoking in 85.7% (12/14 and alcohol (moderate consumption in 64% (9/14 was present in male patients. There was no history of alcohol or smoking was present among female patients. However, tobacco chewing habit was present in 28% (4/14 of female patients. History of multiple sexual partners in 14% (4/28 of cases and 78% (22/28 were non-vegetarians. Nearly 85% (24/28 of patients presented with an advanced stage disease. The analysis showed involvement of left side of colon in 50% (14/28, rectum in 39% (11/28 and right side of colon in 11%(3/28. Except for two patients who were in stage - 1, all other patients received chemotherapy. CONCLUSION The incidence of colorectal cancer in young individuals is constantly rising. The reason for this increase is unclear and the relative contributions of genetic versus environmental factors remain relatively unexplored.
Kim, Myung Se; Kim, Sung Kyu; Kim, Jae Hwang; Kwan, Koing Bo; Kim, Heung Dae
Colorectal cancer is the second most frequent malignant tumor in the United States and fourth most frequent tumor in Korea. Surgery has been used as a primary treatment modality but reported overall survivals after curative resection were from 20% to 50%. Local recurrence is the most common failure in the treatment of locally advanced colorectal cancer. Once recurrence has developed, surgery has rarely the role and the five year survival of locally advanced rectal cancer is less than 5%, this indicated that significant improvement of local control could be achieved. We performed 6 cases of IORT for locally advanced colorectal cancer which is he first experience in Korea. Patient's eligibility, treatment applicator, electron energy, dose distribution on the surface and depth within the treatment field and detailed skills are discussed. We hope that our IORT protocol can reduce local failure and increase the long term survival significantly
Munro, Matthew J; Wickremesekera, Susrutha K; Peng, Lifeng; Tan, Swee T; Itinteang, Tinte
Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. Adenocarcinoma accounts for 90% of CRC cases. There has been accumulating evidence in support of the cancer stem cell (CSC) concept of cancer which proposes that CSCs are central in the initiation of cancer. CSCs have been the focus of study in a range of cancers, including CRC. This has led to the identification and understanding of genes involved in the induction and maintenance of pluripotency of stem cells, and markers for CSCs, including those investigated specifically in CRC. Knowledge of the expression pattern of CSCs in CRC has been increasing in recent years, revealing a heterogeneous population of cells within CRC ranging from pluripotent to differentiated cells, with overlapping and sometimes unique combinations of markers. This review summarises current literature on the understanding of CSCs in CRC, including evidence of the presence of CSC subpopulations, and the stem cell markers currently used to identify and localise these CSC subpopulations. Future research into this field may lead to improved methods for early detection of CRC, novel therapy and monitoring of treatment for CRC and other cancer types. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
S. Saadatmand (Sepideh)
markdownabstract__Abstract__ We estimated influence of tumor size and number of positive lymph nodes at breast cancer detection on survival in the current era of new system (neo) adjuvant therapies. We showed that early breast cancer detection remains of great influence. Relative 5-year survival
Peng, H X; Xu, X; Yang, R; Chu, Y M; Yang, D M; Xu, Y; Zhou, F L; Ma, W Z; Zhang, X J; Guan, M; Yang, Z H; Jin, Z D
Single nucleotide polymorphisms (SNPs) in mismatch repair genes, especially in the MLH1 gene, are closely associated with susceptibility to hereditary nonpolyposis colorectal cancer. However, few relevant findings are available regarding the association between sporadic colorectal cancer (SCRC) and SNPs of MLH1 in Chinese patients. Therefore, the present study aimed to describe the pathogenic association between three important MLH1 polymorphisms and SCRC in the Chinese population. Peripheral blood samples from 156 SCRC patients and 311 healthy controls were collected. DNA was purified from peripheral blood, and the V384D, R217C, and I219V polymorphisms were evaluated using high-resolution melting analysis and direct sequencing. The association between the three important MLH1 polymorphisms and clinical pathological features of the SCRC patients was analyzed. In addition, PMS2-MLH1 protein interactions were determined by co-immunoprecipitation (Co-IP) to determine the protein functional alteration induced by these SNPs. Among the three polymorphisms, V384D was significantly associated with the risk of SCRC (OR = 31.36, P MLH1 R217C, V384D, and I219V variants had relative binding abilities with PMS2 of 0.59, 0.70, and 0.80, respectively, compared with the wild-type. These findings suggest that MLH1 V384D could be a promising genetic marker for susceptibility to SCRC.
Strambu, V; Garofil, D; Pop, F; Radu, P; Bratucu, M; Popa, F
Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.
in the DNA mismatch repair genes hMLH1 and hMSH2, and less frequently hMSH6 and PMS2, leading to the rapid development of neoplasms ..... nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer.
Vannucci, Luca; Fišerová, Anna; Horváth, Ondřej; Rossmann, Pavel; Mosca, F.; Pospíšil, Miloslav
Roč. 25, - (2004), s. 973-981 ISSN 1019-6439 R&D Projects: GA ČR GV312/98/K034; GA AV ČR IAA7020006 Institutional research plan: CEZ:AV0Z5020903 Keywords : cancer * cancer model * colorectal adenocarcinoma Subject RIV: EE - Microbiology, Virology Impact factor: 3.056, year: 2004
Alhopuro, Pia; Sammalkorpi, Heli; Niittymäki, Iina
Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in ∼ 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers...
Early detection of cancer through screening is an important step in decreasing both morbidity and mortality. Likewise, specific modifiable lifestyle behaviors are associated with reduced risk of colorectal cancer. Lifestyle practices have also been shown to maximize health after the primary treatmen...
For localized colorectal cancer (CRC), lymph node metastases are the most powerful prognostic factor for disease specific and overall survival. In the first part of the thesis, we explore the prognostic role of lymph nodes in patients with stage I/II colon cancer. In these patients, nodal metastases
van der Paardt, M.P.
In the first part of this thesis certain aspects of MRI in the evaluation of colorectal cancer and its precursors, and restaging of rectal cancer were addressed. The current status of MR colonography regarding the different preparation techniques as well as the imaging sequences and colon distension
Azizi, Hosein; Asadollahi, Khairollah; Davtalab Esmaeili, Elham; Mirzapoor, Mohammad
Role of diet on colorectal cancer (CRC) has been considered in terms of single foods and nutrients, but less frequently in terms of dietary patterns in Iran. The objective of this study was to determine the association between Iranian dietary patterns and CRC. This case-control study was conducted in four hospitals in Tabriz City of Iran including 414 participants aged 35-75 years:207 cases with CRC confirmed by pathology and colonoscopy findings were selected and 207 controls free of neoplastic conditions and diet-related chronic diseases (from the same hospital at the same period for the cases). Dietary data were assessed using a 123-item semi-quantitative food frequency questionnaire. Two dietary patterns were found by using of Principal Component Analysis (PCA) method;"Healthy pattern"and "Iranian pattern". Multivariate logistic regression analysis was used to estimate adjusted odds ratios (OR) for relationship between dietary patterns and colorectal cancer. After adjusting for confounding factors, the Iranian dietary pattern was significantly associated with an increased odds of colorectal cancer (OR= 1.46; 95% Confidenec Interval (CI)=1.05-2.19) while a reduced odds of colorectal cancer was observed with the Healthy dietary pattern (OR=0.18; 95% CI= 0.091-0.47). Iranian dietary pattern (IDP) seems to increase the odds of colorectal cancer and protective effect of Healthy dietary pattern.
Full Text Available Background: Role of diet on colorectal cancer (CRC has been considered in terms of single foods and nutrients, but less frequently in terms of dietary patterns in Iran. The objective of this study was to determine the association between Iranian dietary patterns and CRC.Methods: This case–control study was conducted in four hospitals in Tabriz City of Iran including 414 participants aged 35–75 years:207 cases with CRC confirmed by pathology and colonoscopy findings were selected and 207 controls free of neoplastic conditions and diet-related chronic diseases (from the same hospital at the same period for the cases. Dietary data were assessed using a 123-item semi-quantitative food frequency questionnaire. Two dietary patterns were found by using of Principal Component Analysis (PCA method;“Healthy pattern”and “Iranian pattern”. Multivariate logistic regression analysis was used to estimate adjusted odds ratios (OR for relationship between dietary patterns and colorectal cancer.Results: After adjusting for confounding factors, the Iranian dietary pattern was significantly associated with an increased odds of colorectal cancer (OR= 1.46; 95% Confidenec Interval (CI=1.05–2.19 while a reduced odds of colorectal cancer was observed with the Healthy dietary pattern (OR=0.18; 95% CI= 0.091-0.47.Conclusion: Iranian dietary pattern (IDP seems to increase the odds of colorectal cancer and protective effect of Healthy dietary pattern.
Randi, Giorgia; Edefonti, Valeria; Ferraroni, Monica; La Vecchia, Carlo; Decarli, Adriano
The association of colorectal cancer risk with select foods has been evaluated by dietary pattern analysis. This review of the literature was conducted to thoroughly examine the available evidence for the association between dietary patterns and colorectal cancers and adenomas. A total of 32 articles based on worldwide epidemiological studies were identified. Pattern identification was achieved by exploratory data analyses (principal component, factor, and cluster analyses) in most articles, and only a few used a priori-defined scores. Dietary patterns named as healthy, prudent, fruit and vegetables, fat-reduced/diet foods, vegetable/fish/poultry, fruit/whole grain/dairy, and healthy eating index-2005, recommended food and Mediterranean diet scores were all associated with reduced risk of colorectal cancer and the risk estimates varied from 0.45 to 0.90. In contrast, diets named Western, pork-processed meat-potatoes, meat-eaters, meat and potatoes, traditional patterns, and dietary risk and life summary scores were associated with increased risk of colorectal cancer with risk estimates varying from 1.18 to 11.7. Dietary patterns for adenomas were consistent with those identified for colorectal cancer.
Normén, A.L.; Brants, H.A.M.; Voorrips, L.E.; Andersson, H.A.; Brandt, P.A. van den
Background: Plant sterols in vegetable foods might prevent colorectal cancer. Objective: The objective was to study plant sterol intakes in relation to colorectal cancer risk in an epidemiologic study. Design: The study was performed within the framework of the Netherlands Cohort Study on Diet and
Sprangers, M. A.
There is increasing recognition of the need to assess the impact of colorectal cancer and its treatment on patients' quality of life (QL). An overview is provided of generic and (colorectal) cancer-specific QL questionnaires that yield adequate levels of reliability and validity. These measures have
Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei
BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p expression in polyps (p ..., no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages...
Wael M. Abdel-Rahman
Full Text Available All colorectal cancer cell lines except RKO displayed active β-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various β-catenin localizations as a surrogate marker for β-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1 confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors with membranous β-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.
Antonio Z. Gimeno García
Full Text Available Colorectal cancer (CRC is a major health problem worldwide. Although population-based CRC screening is strongly recommended in average-risk population, compliance rates are still far from the desirable rates. High levels of screening uptake are necessary for the success of any screening program. Therefore, the investigation of factors influencing participation is crucial prior to design and launches a population-based organized screening campaign. Several studies have identified screening behaviour factors related to potential participants, providers, or health care system. These influencing factors can also be classified in non-modifiable (i.e., demographic factors, education, health insurance, or income and modifiable factors (i.e., knowledge about CRC and screening, patient and provider attitudes or structural barriers for screening. Modifiable determinants are of great interest as they are plausible targets for interventions. Interventions at different levels (patient, providers or health care system have been tested across the studies with different results. This paper analyzes factors related to CRC screening behaviour and potential interventions designed to improve screening uptake.
Zhang, Xueli; Sun, Xiao-Feng; Cao, Yang; Ye, Benchen; Peng, Qiliang; Liu, Xingyun; Shen, Bairong; Zhang, Hong
Castro-Mujica, María del Carmen; Sullcahuamán-Allende, Yasser; Barreda-Bolaños, Fernando; Taxa-Rojas, Luis
Colorectal cancer (CRC) is the fourth most common cancer in the world and is classified according to their origin in sporadic CRC (~ 70%) and genetic CRC (~ 30%), this latter involves cases of familial aggregation and inherited síndromes that predispose to CRC. To describe inherited CRC predisposition syndromes, polyposic and non-polyposic, identified in the Oncogenetics Unit at National Institute of Cancer Disease (INEN). A descriptive observational record from the attentions of the Oncogenetics Unit at INEN during 2009 to 2013. We included patients with personal or familiar history of CRC and/or colonic polyposis who were referred for clinical assessment to the Oncogenetics Unitat INEN. 59.3 % were female, 40.7 % male, 69.8% under 50 years old, 60.5% had a single CRC, 23.2% had more than one CRC or CRC associated with other extracolonic neoplasia and 32.6% had a familiar history of cancer with autosomal dominant inheritance. According to the clinical genetic diagnosis, 93.1% of the included cases were inherited syndromes that predispose to CRC, with 33.8% of colonic polyposis syndromes, 23.3% of hereditary nonpolyposis CRC syndromes (HNPCC) and 36.0% of CCRHNP probable cases. Clinical genetic evaluation of patients with personal or familiar history of CRC and/or colonic polyposis can identify inherited colorectal cancer predisposition syndromes and provide an appropriategenetic counseling to patients and relatives at risk, establishing guidelines to follow-up and prevention strategies to prevent morbidity and mortality by cancer.
Perrigue, Martine M; Kantor, Elizabeth D; Hastert, Theresa A; Patterson, Ruth; Potter, John D; Neuhouser, Marian L; White, Emily
Eating frequency is a modifiable aspect of dietary behavior that may affect risk of colorectal cancer (CRC). Although most previous case-control studies indicate a positive association, two prospective studies suggest an inverse association between eating frequency and CRC risk, with evidence of effect modification by diet composition. We examined the association between eating frequency and CRC in a large, prospective cohort study, and explored whether this relationship was modified by sex, coffee consumption, or dietary glycemic load. Between 2000 and 2002, 67,912 western Washington residents aged 50-76 reported average daily meal and snack frequency using a mailed questionnaire as part of the vitamins and lifestyle study. Participants were followed for CRC through linkage with SEER through 2008, over which time 409 CRC cases developed. Hazard Ratios and 95 % Confidence Intervals were obtained using Cox regression. In age- and sex-adjusted models higher (5+ times/d) vs. lower (1-2 times/d) eating frequency was associated with a HR of 0.62 (95 % CI 0.43-0.88, Ptrend = 0.001). However, following further adjustment for BMI, race/ethnicity, alcohol, and other known CRC risk factors, the relationship was no longer statistically significant (HR: 0.76; 95 % CI 0.51, 1.14). No effect modification was observed by sex (Pinteraction = 0.45), coffee consumption (Pinteraction = 0.44), or dietary glycemic load (Pinteraction = 0.90). In subgroup analyses by tumor site, higher vs. lower eating frequency was associated with lower risk for colon (HR 0.65 95 % CI 0.39-1.07, Ptrend = 0.04), but not rectal cancers (HR = 1.08 95 % CI 0.54-2.18, Ptrend = 0.94). The weak inverse association observed between eating frequency and CRC is consistent with findings from other prospective studies. Modification of this relationship by diet quality and participant characteristics should be considered in the future studies.
Zeichner, Simon B; Stanislaw, Christine; Meisel, Jane L
In recent years, we have learned a great deal about pathogenic mutations that increase the risk of breast and ovarian cancer, particularly mutations in the BRCA1 and BRCA2 genes. Here we review current guidelines on breast and ovarian cancer screening, prophylactic surgery, and other risk-reduction strategies in patients with these mutations, and we detail the data that drive these recommendations. We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer. Discussions about genetic testing have become more complex with the advent of panel testing, which often allows for testing of a more comprehensive panel of genes than traditional BRCA1 and BRCA2 testing, but which is also associated with a higher likelihood of obtaining results with less clear data to inform management. It is difficult to come to a consensus on how best to address the varied and potentially challenging situations that may arise from genetic testing. The complexity inherent in managing these cases makes a multidisciplinary team-including medical oncologists, surgical oncologists, genetic counselors, reproductive endocrinologists, and medical ethicists-critical to optimization of care.
In recent years, the effects of biliverdin and bilirubin have been studied extensively, and an inhibitory effect of bile pigments in cancer progression has been proposed. In this study we focused on the effects of biliverdin reductase, the enzyme that converts biliverdin to bilirubin, in colorectal cancer. For in vitro experiments we used a human colorectal carcinoma cell line and transfected it with an expression construct of shRNA specific for biliverdin reductase, to create cells with stable knock-down of enzyme expression. Cell proliferation was analyzed using the CASY model TT cell counting device. Western blot protein analysis was performed to study intracellular signaling cascades. Samples of human colorectal cancer were analyzed using immunohistochemistry. We were able to confirm the antiproliferative effects of bile pigments on cancer cells in vitro. However, this effect was attenuated in biliverdin reductase knock down cells. ERK and Akt activation seen under biliverdin and bilirubin treatment was also reduced in biliverdin reductase deficient cells. Immunohistochemical analysis of tumor samples from patients with colorectal cancer showed elevated biliverdin reductase levels. High enzyme expression was associated with lower overall and disease free patient survival. We conclude that BVR is required for bile pigment mediated effects regarding cancer cell proliferation and modulation of intracellular signaling cascades. The role of BVR overexpression in vivo and its exact influence on cancer progression and patient survival need to be further investigated. (author) [de
Hadjiliadis, Denis; Khoruts, Alexander; Zauber, Ann G; Hempstead, Sarah E; Maisonneuve, Patrick; Lowenfels, Albert B
Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5-10 times greater compared to the general population, and 25-30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations. The 18-member task force consisted of experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3 workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February-March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159 articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modeling Network. The task force included recommendation statements in the final guideline only if they reached an 80% acceptance threshold. The task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unless shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening
Rigter, Lisanne S; Spaander, Manon C W; Moons, Leon M; Bisseling, Tanya M; Aleman, Berthe M P; de Boer, Jan Paul; Lugtenburg, Pieternella J; Janus, Cecile P M; Petersen, Eefke J; Roesink, Judith M; Raemaekers, John M M; van der Maazen, Richard W M; Cats, Annemieke; Bleiker, Eveline M A; Snaebjornsson, Petur; Carvalho, Beatriz; Lansdorp-Vogelaar, Iris; Jóźwiak, Katarzyna; Te Riele, Hein; Meijer, Gerrit A; van Leeuwen, Flora E; van Leerdam, Monique E
BACKGROUND: Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy
Joost, Patrick; Veurink, Nynke; Holck, Susanne
BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...
Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn
BACKGROUND: The past years' therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently......, panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...
Wiedenbein, Liza; Kristiansen, Maria; Adamsen, Lis
clinical practices related to identification and documentation of rehabilitation needs among patients with colorectal cancer at Danish hospitals. Material and methods A retrospective clinical audit was conducted utilizing data from patient files randomly selected at surgical and oncology hospital...... departments treating colorectal cancer patients. Forty patients were included, 10 from each department. Semi-structured interviews were carried out among clinical nurse specialists. Audit data was analyzed using descriptive statistics, qualitative data using thematic analysis. Results Documentation...... rehabilitation services was documented among 5% (n = 2) of all patients. Assessments at surgical departments were shaped by the inherent continuous assessment of rehabilitation needs within standardized fast-track colorectal cancer surgery. In contrast, the implementation of locally developed assessment tools...
K. V. Rachkovsky
Full Text Available The purpose of the study was a review of available data on the role of autophagy and angiogenesis in the development, progression and prognosis of colorectal cancer. Material and methods. Databases searched were Medline, Cochrane Library and Elibrary. Of 340 studies, 48 were used to write a systematic review. Results. To date, there is a variety of prognostic markers used in the study of pathogenesis, diagnosis and treatment of colorectal cancer. The review describes the molecular mechanisms of the participation of various proteins of autophagy and angiogenesis in the pathogenesis and progression of colorectal cancer, and the potential importance of their use in clinical practice is presented. Conclusion. Many of the existing markers can be used not only in assessing the prognosis, but also sensitivity to chemotherapy. However, the contradictory results of studies with respect to certain proteins require further study, validation, and subsequent introduction into practice.
Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt
Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc.1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... Hospital, Vejle, Denmark4Institute of Regional Health Services Research, University of Southern Denmark, Odense DenmarkBackgroundPrognostic and predictive markers are needed for individualizing the treatment of colorectal cancer. Hypoxia-inducible factor 1α (HIF-1α) is a transcription-inducing factor which...... the predictive and prognostic value of HIF-1α in colorectal cancer.Materials and MethodsThe project is divided into 3 substudies:1. Biological and methodological aspects. The expression of HIF-1α measured by immunohistochemistry in paraffin embedded tissue is related to single nucleotide polymorphism (SNP...
Schubert, S.A.; Ruano, D.; Elsayed, F.A.; Boot, A.; Crobach, S.; Sarasqueta, A.F.; Wolffenbuttel, B.; van der Klauw, M.M.; Oosting, J.; Tops, C.M.; van Eijk, R.; Vasen, H.F.; Vossen, R.H.; Nielsen, M.; Castellví-Bel, S.; Ruiz-Ponte, C.; Tomlinson, I.; Dunlop, M.G.; Vodička, Pavel; Wijnen, J.T.; Hes, F.J.; Morreau, H.; de Miranda, N.F.; Sijmons, R.H.; van Wezel, T.
Roč. 117, č. 8 (2017), s. 1215-1223 ISSN 0007-0920 R&D Projects: GA MŠk(CZ) LD14050 Institutional support: RVO:68378041 Keywords : hereditary colorectal cancer * colorectal polyps * homozygosity mapping Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.176, year: 2016
Bleiker Eveline MA
Full Text Available Abstract Background This study examined: (1 levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC; (2 associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3 the impact of genetic counselling on family relationships, and (4 social consequences of genetic counselling. Methods In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986–1998 completed a self-report questionnaire by mail. Results 116 individuals (81% response rate completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES. Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%, family relationships (5%, obtaining life insurance (8%, choice or change of jobs (2%, and obtaining a mortgage (2%. Conclusion On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.
Kriza, Christine; Emmert, Martin; Wahlster, Philip; Niederländer, Charlotte; Kolominsky-Rabas, Peter
Given the current-and increasing-pressure to limit expenditure on health care provision in many countries, a better understanding of the cost burden of colorectal cancer is needed. Cost-of-illness studies and reviews thereof can be a useful tool for analysing and critically evaluating the cost-related development of colorectal cancer, and they highlight important cost drivers. A systematic review was conducted from 2002 to 2012 to identify cost-of-illness studies related to colorectal cancer, searching the Medline, PubMed, Science Direct, Cochrane Library and the York CRD databases. Among the 10 studies (from France, the US, Ireland and Taiwan) included in the review, 6 studies reported prevalence-based estimates and 4 studies focussed on incidence-based data. In the studies included in the review, long-term costs for colorectal cancer of up to $50,175 per patient (2008 values) were estimated. Most of the studies in the review showed that the initial and terminal phases of colorectal cancer care are the most expensive, with continuing treatment being the least costly phase. One study also highlighted that stage I CRC disease was the least costly and stage III the most costly of all 4 stages, due to the high cost impact of biological agents. This review has highlighted a trend for rising costs associated with CRC, which is linked to the increasing use of targeted biological therapies. COI studies in colorectal cancer can identify specific components and areas of care that are especially costly, thereby focussing attention on more cost-effective approaches, which is especially relevant to the increased use of biological agents in the field of personalised medicine. COI studies are an important tool for further health economic evaluations of personalised medicine.
Kim, Myung Se; Lee, Joon Ha
In spite of remarkable improvement of surgical skills and anesthesia, local failure still occurred in 36-45% of locally advanced colorectal cancer after curative resection with or without pre-or post-operative irradiation. Intraoperative radiation therapy (IORT) is the ideal modality which respectable lesions are removed surgically and the remaining cancer nests are sterilized by irradiation during a surgical procedure. Therefore, the excellent local control without the damage of the adjacent normal tissues can be achieved. In IORT, judicious set up of the treatment cone on the treatment surface of the patient is required for accurate and homogenous dose distribution within treatment field, especially on the slopping surface of sacrum and pelvic sidewall which are the common sites of the local recurrence in rectal cancer. For this purpose, adequate coordination of gantry rotation and table tilting are essential. Adjusting gantry rotation is not difficult but tilting of the table is impossible inconventional treatment couch. Department of Therapeutic Radiology in Yeungnam University Medical Center developed the IORT table for colorectal cancer which is easy to set up and detach on head-down is about 30 degree which is efficient and easy-to-use, not only for IORT but also for colorectal surgery. So far, authors performed IORT with newly developed treatment table in 2 patients with rectal cancer and we found that this newly developed table could contribute in improving the dose distribution of IORT and surgical procedure for colorectal cancer
S. N. Shchaeva
Full Text Available Objective: to assess the immediate results of surgical interventions for colorectal cancer complicated by perforation.Materials and methods. The immediate results of surgical treatment were retrospectively analyzed in 56 patients with colorectal cancer complicated by perforated colon cancer, who had been treated at Smolensk surgical hospitals in 2001 to 2013. Patients with diastatic perforation of the colon in the presence of decompensated obturation intestinal obstruction of tumor genesis were not included into this investigation.Results. The immediate results of uni- and multistage surgical interventions were analyzed in relation to the extent of peritonitis and the stage of colon cancer. More satisfactory immediate results were observed after multistage surgical treatment. Following these interventions, a fatal outcome of disseminated peritonitis in the presence of performed colorectal cancer was recorded in 8 (53.3 % cases whereas after symptomatic surgery there were 11 (67.8 % deaths. A fatal outcome was noted in 1 case (7.7 % after multistage surgery.Discussion. The results of surgical treatment in the patients with perforated colorectal cancer are directly related to the degree of peritonitis and the choice of surgical tactics.
Hundahl Scott A
Full Text Available Abstract Background Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. Methods Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese. The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. Results Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. Conclusion Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated.
Ryska, M; Bauer, J
Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.