Colorectal cancer in patients with inflammatory bowel disease

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Andersen, Vibeke; Halfvarson, Jonas; Vogel, Ulla Birgitte

2012-01-01

The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed C...... preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.......The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC...... during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing...

Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

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Eva Pastille

2017-09-01

Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

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Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

2016-05-27

Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective study of blood metabolites associated with colorectal cancer risk.

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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

2018-02-26

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.

Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway

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Wang, Xin; Mandal, Ardhendu K. [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Saito, Hiroshi [Department of Surgery and Physiology, Lucille P. Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Pulliam, Joseph F.; Lee, Eun Y. [Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536 (United States); Ke, Zun-Ji; Lu, Jian; Ding, Songze [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Li, Li [Department of Family Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Shelton, Brent J.; Tucker, Thomas [Markey Cancer Control Program, University of Kentucky, Lexington, KY 40504 (United States); Evers, B. Mark [Department of Surgery and Physiology, Lucille P. Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

2012-07-01

Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway. -- Highlights: ► Carcinogenic metals in drinking water promote colorectal tumor formation in vivo. ► Carcinogenic metals induce β-catenin activation in vivo and in vitro. ► ROS generation induced by carcinogenic metals mediated β-catenin activation.

Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway

International Nuclear Information System (INIS)

Wang, Xin; Mandal, Ardhendu K.; Saito, Hiroshi; Pulliam, Joseph F.; Lee, Eun Y.; Ke, Zun-Ji; Lu, Jian; Ding, Songze; Li, Li; Shelton, Brent J.; Tucker, Thomas; Evers, B. Mark; Zhang, Zhuo; Shi, Xianglin

2012-01-01

Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway. -- Highlights: ► Carcinogenic metals in drinking water promote colorectal tumor formation in vivo. ► Carcinogenic metals induce β-catenin activation in vivo and in vitro. ► ROS generation induced by carcinogenic metals mediated β-catenin activation.

MDSCs are involved in the protumorigenic potentials of GM-CSF in colitis-associated cancer.

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Ma, Ning; Liu, Qilin; Hou, Lin; Wang, Yalin; Liu, Ziling

2017-06-01

Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation. Importantly, this MDSC accumulation was controlled by GM-CSF. MDSC number decreased significantly in GM-CSF-deficient mice suffering from CAC induction, and transfusion of MDSCs from wild-type CAC-bearing mice into GM-CSF-deficient counterparts led to recurrence of CAC. Furthermore, the supernatants of CAC lesions or GM-CSF alone was sufficient to differentiate hematopoietic precursors into MDSCs. Addition of neutralizing anti-GM-CSF antibody impaired the MDSC-differentiating effects of the supernatants of CAC lesions. Overall, these findings shed new insights into the mechanisms of GM-CSF underlying CAC development, by inducing/recruiting CAC-promoting MDSCs. Blocking GM-CSF activity or MDSC function may represent new therapeutic strategies for CAC in clinic.

5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

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Li-Na Zhao

Full Text Available BACKGROUND: Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. METHODS: Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI. Publication bias and heterogeneity were assessed. RESULTS: Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84. Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. CONCLUSION: Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

Hemidesmosome integrity protects the colon against colitis and colorectal cancer.

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De Arcangelis, Adèle; Hamade, Hussein; Alpy, Fabien; Normand, Sylvain; Bruyère, Emilie; Lefebvre, Olivier; Méchine-Neuville, Agnès; Siebert, Stéphanie; Pfister, Véronique; Lepage, Patricia; Laquerriere, Patrice; Dembele, Doulaye; Delanoye-Crespin, Anne; Rodius, Sophie; Robine, Sylvie; Kedinger, Michèle; Van Seuningen, Isabelle; Simon-Assmann, Patricia; Chamaillard, Mathias; Labouesse, Michel; Georges-Labouesse, Elisabeth

2017-10-01

Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the α6β4 integrin receptor found in hemidesmosomes that attach intestinal epithelial cells (IECs) to the laminin-containing BM. We developed new mouse models inducing IEC-specific ablation of α6 integrin either during development (α6 ΔIEC ) or in adults (α6 ΔIEC-TAM ). Strikingly, all α6 ΔIEC mutant mice spontaneously developed long-standing colitis, which degenerated overtime into infiltrating adenocarcinoma. The sequence of events leading to disease onset entails hemidesmosome disruption, BM detachment, IL-18 overproduction by IECs, hyperplasia and enhanced intestinal permeability. Likewise, IEC-specific ablation of α6 integrin induced in adult mice (α6 ΔIEC-TAM ) resulted in fully penetrant colitis and tumour progression. Whereas broad-spectrum antibiotic treatment lowered tissue pathology and IL-1β secretion from infiltrating myeloid cells, it failed to reduce Th1 and Th17 response. Interestingly, while the initial intestinal inflammation occurred independently of the adaptive immune system, tumourigenesis required B and T lymphocyte activation. We provide for the first time evidence that loss of IECs/BM interactions triggered by hemidesmosome disruption initiates the development of inflammatory lesions that progress into high-grade dysplasia and carcinoma. Colorectal neoplasia in our mouse models resemble that seen in patients with IBD, making them highly attractive for discovering more efficient therapies. Published by the BMJ Publishing Group Limited. For permission to use (where

Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

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Wunderlich, Claudia M; Ackermann, P Justus; Ostermann, Anna Lena; Adams-Quack, Petra; Vogt, Merly C; Tran, My-Ly; Nikolajev, Alexei; Waisman, Ari; Garbers, Christoph; Theurich, Sebastian; Mauer, Jan; Hövelmeyer, Nadine; Wunderlich, F Thomas

2018-04-25

Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.

Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

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Emily L Lowe

2010-09-01

Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

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2017-08-01

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

The prevalence of inflammatory bowel diseases, microscopic colitis, and colorectal cancer in patients with irritable bowel syndrome

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Magdy El-Salhy

2011-07-01

Full Text Available The diagnosis of irritable bowel syndrome (IBS is symptom-based and experts have developed diagnostic criteria for IBS. Distinguishing inflammatory bowel diseases (IBD from IBS, especially with mild disease activity, can be difficult. Another concern is microscopic colitis (MC. MC and IBS have similar symptoms and a normal endoscopic appearance. Our study investigated the prevalence of patients with IBD, MC, and colorectal cancer among 968 patients that fulfill the Rome III criteria for IBS. Among these patients, four were found with IBD (0.4% and seven with MC (0.7%. Among the IBD patients, three suffered from Crohn’s disease, affecting the terminal ileum, and one with ulcerative rectosigmoiditis. Of the seven patients with MC, two had collagenous colitis and five had lymphocytic colitis. Two IBS diarrhea-predominant patients had adenocarcin­oma in the sigmoid colon. These patients were a female aged 58 years and a male aged 56 years. We concluded from our study and earl­ier studies that symptom-based diagnosis of IBS may lead to missing a number of other gastrointestinal disorders that require quite different management than that for IBS.

Ischaemic colitis associated with carcinoma of the colon

International Nuclear Information System (INIS)

Reeders, J.W.A.; Rosenbusch, B.; Tytgat, G.N.J.

1982-01-01

In a retrospective study of one hundred and seventy patients with ischaemic colitis, we found eight patients with partially obstructive carcinoma of the colon located distally, seven located in the sigmoid and one in the splenic flexure. The frequency of this association (1-4.7% in the literature and 5.3% in our series) requires careful examination by radiologist and surgeon. The radiologist should be alert to the association of ischaemic damage proximal to an obstructive colorectal cancer. The surgeon must examine any colonic segment removed for carcinoma in order to exclude an ischaemic process in the area of the anastomosis and prevent leakage at the anastomosis or stricture formation. (orig.)

Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE{sub 2} and IL-6

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Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Xinhua [Department of Liver, Biliary And Pancreatic Tumors, Hubei Cancer Hospital, Wuhan 430079 (China); Chen, Xuewei; Li, Ying; Ke, Zunqiong [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Chen, Honglei, E-mail: hl-chen@whu.edu.cn [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

2014-09-15

M2 macrophage polarization is implicated in colorectal cancer development. Isoliquiritigenin (ISL), a flavonoid from licorice, has been reported to prevent azoxymethane (AOM) induced colon carcinogenesis in animal models. Here, in a mouse model of colitis-associated tumorigenesis induced by AOM/dextran sodium sulfate (DSS), we investigated the chemopreventive effects of ISL and its mechanisms of action. Mice were treated with AOM/DSS and randomized to receive either vehicle or ISL (3, 15 and 75 mg/kg). Tumor load, histology, immunohistochemistry, and gene and protein expressions were determined. Intragastric administration of ISL for 12 weeks significantly decreased colon cancer incidence, multiplicity and tumor size by 60%, 55.4% and 42.6%, respectively. Moreover, ISL inhibited M2 macrophage polarization. Such changes were accompanied by downregulation of PGE{sub 2} and IL-6 signaling. Importantly, depletion of macrophages by clodronate (Clod) or zoledronic acid (ZA) reversed the effects of ISL. In parallel, in vitro studies also demonstrated that ISL limited the M2 polarization of RAW264.7 cells and mouse peritoneal macrophages with concomitant inactivation of PGE{sub 2}/PPARδ and IL-6/STAT3 signaling. Conversely, exogenous addition of PGE{sub 2} or IL-6, or overexpression of constitutively active STAT3 reversed ISL-mediated inhibition of M2 macrophage polarization. In summary, dietary flavonoid ISL effectively inhibits colitis-associated tumorigenesis through hampering M2 macrophage polarization mediated by the interplay between PGE{sub 2} and IL-6. Thus, inhibition of M2 macrophage polarization is likely to represent a promising strategy for chemoprevention of colorectal cancer. - Highlights: • Isoliquiritigenin (ISL) prevents colitis-associated tumorigenesis. • ISL inhibits M2 macrophage polarization in vivo and in vitro. • ISL inhibits PGE{sub 2} and IL-6 signaling in colitis-associated tumorigenesis. • ISL may be an attractive candidate agent for

Analysis of metastasis associated signal regulatory network in colorectal cancer.

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Qi, Lu; Ding, Yanqing

2018-06-18

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.

Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.

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Sun, Guochuan; Zheng, Zongping; Lee, Mee-Hyun; Xu, Yijuan; Kang, Soouk; Dong, Zigang; Wang, Mingfu; Gu, Zhennan; Li, Haitao; Chen, Wei

2017-05-03

Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

Association between phytosterol intake and colorectal cancer risk: a case-control study.

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Huang, Jing; Xu, Ming; Fang, Yu-Jing; Lu, Min-Shan; Pan, Zhi-Zhong; Huang, Wu-Qing; Chen, Yu-Ming; Zhang, Cai-Xia

2017-03-01

A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trendphytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

Colonoscopy surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel disease

DEFF Research Database (Denmark)

Aalykke, Claus; Jensen, Michael Dam; Fallingborg, Jan

2015-01-01

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients......, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative...... colitis; and patients with ulcerative colitis as well as Crohn´s disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted...

Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

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Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

2009-01-01

ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

Sugars, sucrose and colorectal cancer risk: the Fukuoka colorectal cancer study.

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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

2014-05-01

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.

Colitis ulcerosa

DEFF Research Database (Denmark)

Nielsen, Ole Haagen; Jess, Tine; Bjerrum, Jacob Tveiten

2013-01-01

Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of th......Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer...... is of the same magnitude as in the background population. The symptoms are usually diarrhoea including bloody stools, rectal tenesmi, anaemia, and fatigue. This review is an update on diagnostics and treatment strategies of relevance for clinicians, and as UC often affects patients during their peak reproductive...

Cytomegalovirus colitis after systemic chemotherapy in a patient with recurrent colon cancer: A case report

Directory of Open Access Journals (Sweden)

Teraishi Fuminori

2008-08-01

Full Text Available Abstract Introduction The occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear. Case presentation We present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually. Conclusion The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

Colorectal cancer complicating Crohn's disease.

Science.gov (United States)

Freeman, H J

2001-04-01

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.

Colorectal Cancer Complicating Crohn's Disease

Directory of Open Access Journals (Sweden)

Hugh J Freeman

2001-01-01

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.

Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer.

OpenAIRE

Gibson, P; Rosella, O; Nov, R; Young, G

1995-01-01

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 h...

Genetic variations in SMAD7 are associated with colorectal cancer risk in the colon cancer family registry.

Directory of Open Access Journals (Sweden)

Xuejuan Jiang

Full Text Available Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry.23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression.Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49, and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92 were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps.SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.

Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

Science.gov (United States)

Urrutia-Ortega, Ismael M; Garduño-Balderas, Luis G; Delgado-Buenrostro, Norma L; Freyre-Fonseca, Verónica; Flores-Flores, José O; González-Robles, Arturo; Pedraza-Chaverri, José; Hernández-Pando, Rogelio; Rodríguez-Sosa, Miriam; León-Cabrera, Sonia; Terrazas, Luis I; van Loveren, Henk; Chirino, Yolanda I

2016-07-01

Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

An inverse association between tea consumption and colorectal cancer risk.

Science.gov (United States)

Chen, Yuetong; Wu, Yuan; Du, Mulong; Chu, Haiyan; Zhu, Lingjun; Tong, Na; Zhang, Zhengdong; Wang, Meilin; Gu, Dongying; Chen, Jinfei

2017-06-06

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.

Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer

International Nuclear Information System (INIS)

Maeda, Shin; Hikiba, Yohko; Shibata, Wataru; Ohmae, Tomoya; Yanai, Ayako; Ogura, Keiji; Yamada, Shingo; Omata, Masao

2007-01-01

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-κB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-κB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer

Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

Science.gov (United States)

Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

2015-12-01

Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

Association between Fusobacterium nucleatum and colorectal cancer: Progress and future directions

Science.gov (United States)

Zhang, Sheng; Cai, Sanjun; Ma, Yanlei

2018-01-01

The initiation and progression of colorectal cancer (CRC) involves genetic and epigenetic alterations influenced by dietary and environmental factors. Increasing evidence has linked the intestinal microbiota and colorectal cancer. More recently, Fusobacterium nucleatum (Fn), an opportunistic commensal anaerobe in the oral cavity, has been associated with CRC. Several research teams have reported an overabundance of Fn in human CRC and have elucidated the possible mechanisms by which Fn is involved in colorectal carcinogenesis in vitro and in mouse models. However, the mechanisms by which Fn promotes colorectal carcinogenesis remain unclear. To provide new perspectives for early diagnosis, the identification of high risk populations and treatment for colorectal cancer, this review will summarize the relative research progresses regarding the relationship between Fn and colorectal cancer. PMID:29760804

Neoplasia yield and colonoscopic workload of surveillance regimes for colorectal cancer in colitis patients: a retrospective study comparing the performance of the updated AGA and BSG guidelines.

Science.gov (United States)

Mooiweer, Erik; van der Meulen, Andrea E; van Bodegraven, Adriaan A; Jansen, Jeroen M; Mahmmod, Nofel; Nijsten, Joyce; van Oijen, Martijn G H; Siersema, Peter D; Oldenburg, Bas

2013-11-01

Due to the increased risk of colorectal cancer, colonoscopic surveillance is recommended for patients with ulcerative and Crohn's colitis. Because surveillance intervals differ considerably between the recently updated American Gastroenterological Association (AGA) and British Society of Gastroenterology (BSG) guidelines, we compared the neoplasia yield and colonoscopic workload of these guidelines. Patients with inflammatory bowel disease undergoing surveillance were identified using medical records. Patients were stratified according to the BSG and AGA guidelines, and corresponding colonoscopic workload was calculated based on the risk factors present during follow-up. The incidence of colitis-associated neoplasia (CAN), defined as a low-grade dysplasia in flat mucosa or a non-adenoma-like mass, high-grade dysplasia, or colorectal cancer was compared between the risk groups of either guidelines. In total, 1018 patients with inflammatory bowel disease who underwent surveillance were identified. Using the AGA surveillance intervals, 64 patients (6%) were assigned to annual and 954 patients (94%) to biannual surveillance, resulting in 541 colonoscopies per year. The yield of CAN was 5.3% and 20.3% in the low- and high-risk groups, respectively (P = 0.02). Using the BSG surveillance intervals, 204 patients received surveillance annually (20%), 393 patients every 3 years (39%), and 421 patients every 5 years (41%), resulting in 420 colonoscopies per year, which is 22% lower than the AGA guidelines. The yield of CAN was 3.6%, 6.9%, and 10.8%, for the low-, intermediate-, and high-risk groups, respectively (P = 0.26). Although the BSG surveillance intervals offer the advantage of a lower colonoscopic workload, the risk stratification of the AGA seems superior in distinguishing patients at higher risk of CAN.

Human FK506 binding protein 65 is associated with colorectal cancer

DEFF Research Database (Denmark)

Olesen, Sanne Harder; Christensen, Lise Lotte; Sørensen, Flemming Brandt

2005-01-01

We initiated the present study to identify new genes associated with colorectal cancer. In a previously published microarray study an EST (W80763), later identified as the gene hFKBP10 (NM_021939), was found to be strongly expressed in tumors while absent in the normal mucosa. Here we describe...... this gene hFKBP10 together with its encoded protein hFKBP65 as a novel marker associated with colorectal cancer. Analysis of 31 colorectal adenocarcinomas and 14 normal colorectal mucosa by RealTime PCR for hFKBP10 showed a significant up-regulation in tumors, when compared with normal mucosa....... Immunohistochemical analysis of 26 adenocarcinomas and matching normal mucosa, as well as benign hyperplastic polyps and adenomas, using a monoclonal anti-hFKBP65 antibody, showed that the protein was not present in normal colorectal epithelial cells, but strongly expressed in the tumor cells of colorectal cancer...

Cyr61 Expression is associated with prognosis in patients with colorectal cancer

International Nuclear Information System (INIS)

Jeong, Dongjun; Soo Lee, Moon; Kim, Chang-Jin; Jun Baek, Moo; Heo, Suhak; Sung Ahn, Tae; Lee, Sookyoung; Park, Soyoung; Kim, Hyungjoo; Park, Doosan; Byung Bae, Sang; Lee, Sung Soo

2014-01-01

Cysteine-rich 61 (Cyr61), a member of the CCN protein family, possesses diverse functionality in cellular processes such as adhesion, migration, proliferation, and survival. Cyr61 can also function as an oncogene or a tumour suppressor, depending on the origin of the cancer. Only a few studies have reported Cyr61 expression in colorectal cancer. In this study, we assessed the Cyr61 expression in 251 colorectal cancers with clinical follow up. We examined Cyr61 expression in 6 colorectal cancer cell lines (HT29, Colo205, Lovo, HCT116, SW480, SW620) and 20 sets of paired normal and colorectal cancer tissues by western blot. To validate the association of Cyr61 expression with clinicopathological parameters, we assessed Cyr61 expression using tissue microarray analysis of primary colorectal cancer by immunohistochemical analysis. We verified that all of the cancer cell lines expressed Cyr61; 2 cell lines (HT29 and Colo205) demonstrated Cyr61 expression to a slight extent, while 4 cell lines (Lovo, HCT116, SW480, SW620) demonstrated greater Cyr61 expression than HT29 and Colo205 cell lines. Among the 20 cases of paired normal and tumour tissues, greater Cyr61 expression was observed in 16 (80%) tumour tissues than in normal tissues. Furthermore, 157 out of 251 cases (62.5%) of colorectal cancer examined in this study displayed strong Cyr61 expression. Cyr61 expression was found to be associated with pN (p = 0.018). Moreover, Cyr61 expression was associated with statistically significant cancer-specific mortality (p = 0.029). The duration of survival was significantly lesser in patients with Cyr61 high expression than in patients with Cyr61 low expression (p = 0.001). These results suggest that Cyr61 expression plays several important roles in carcinogenesis and may also be a good prognostic marker for colorectal cancer. Our data confirmed that Cyr61 was expressed in colorectal cancers and the expression was correlated with worse prognosis of colorectal cancers

Current status of research on microRNA associated with colorectal cancer liver metastasis

Directory of Open Access Journals (Sweden)

WANG Dongxu

2016-12-01

Full Text Available Tumor metastasis is a complicated process with multiple steps, and liver metastasis is the most common metastatic mode of colorectal cancer. Deep understanding and study of metastatic mechanism helps to find solutions for colorectal cancer liver metastasis. Recent studies have shown that microRNA are involved in tumor metastasis and recurrence, and studies on microRNA associated with colorectal cancer liver metastasis can provide new thoughts for the development and progression, diagnosis and treatment, and prognosis of the disease. This article summarizes the research advances in microRNA associated with colorectal cancer liver metastasis and reviews the biological function and molecular mechanism of microRNA, which suggests that microRNA have a vital significance in the field of tumor metastasis, especially colorectal cancer liver metastasis.

Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia

Czech Academy of Sciences Publication Activity Database

Švec, J.; Musílková, Jana; Bryndová, Jana; Jirásek, T.; Mandys, V.; Kment, M.; Pácha, Jiří

2010-01-01

Roč. 16, č. 7 (2010), s. 1127-1137 ISSN 1078-0998 R&D Projects: GA MZd(CZ) 1A8651; GA MZd(CZ) NS9982; GA AV ČR(CZ) IAA500110605 Institutional research plan: CEZ:AV0Z50110509 Keywords : ulcerative colitis * colorectal cancer Subject RIV: FD - Oncology ; Hematology Impact factor: 4.613, year: 2010

Demographic factors associated with knowledge of colorectal cancer symptoms in a UK population-based survey.

OpenAIRE

Yardley, C.; Glover, C.; Allen-Mersh, T. G.

2000-01-01

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...

Gallstones and colorectal cancer

DEFF Research Database (Denmark)

Jørgensen, Torben; Rafaelsen, Søren Rafael

1992-01-01

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...

Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

DEFF Research Database (Denmark)

Song, H.; Koessler, T.; Ahmed, S.

2008-01-01

allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

Advanced colonic cancer associated with radiation colitis, report of a case

Energy Technology Data Exchange (ETDEWEB)

Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Matsumoto, Takayuki [Kyushu Univ., Fukuoka (Japan). Hospital

2002-07-01

A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

Advanced colonic cancer associated with radiation colitis, report of a case

International Nuclear Information System (INIS)

Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo; Matsumoto, Takayuki

2002-01-01

A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

Hereditary colorectal cancer diagnostics

DEFF Research Database (Denmark)

Klarskov, Louise; Holck, Susanne; Bernstein, Inge

2012-01-01

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...

Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

Science.gov (United States)

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

2017-12-13

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.

Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women.

Science.gov (United States)

Tabung, Fred K; Liu, Li; Wang, Weike; Fung, Teresa T; Wu, Kana; Smith-Warner, Stephanie A; Cao, Yin; Hu, Frank B; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L

2018-03-01

Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers. Cohort study of 46 804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women (Nurses' Health Study: 1984-2012) followed for 26 years to examine associations between EDIP scores and colorectal cancer risk using Cox regression. We also examined associations in categories of alcohol intake and body weight. Data analysis began January 17, 2017, and was completed August 9, 2017. EDIP scores calculated from food frequency questionnaires administered every 4 years. Incident colorectal cancer. We documented 2699 incident colorectal cancer cases over 2 571 831 person-years of follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80 (women), those in the highest Q had an incidence rate of 151 (men) and 92 (women), leading to an unadjusted rate difference of 38 and 12 more colorectal cancer cases, respectively, among those consuming highly proinflammatory diets. Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR], 1.44; 95% CI, 1.19-1.74; P colorectal cancer. In both men and women, associations were observed in all anatomic subsites except for the rectum in women. In subgroups (P ≤ .02 for all interactions), associations differed by alcohol intake level, with stronger associations among men (Q5 vs Q1 HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1

Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies

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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.

2018-01-01

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

Association between the neighborhood obesogenic environment and colorectal cancer risk in the Multiethnic Cohort.

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Canchola, Alison J; Shariff-Marco, Salma; Yang, Juan; Albright, Cheryl; Hertz, Andrew; Park, Song-Yi; Shvetsov, Yurii B; Monroe, Kristine R; Le Marchand, Loïc; Gomez, Scarlett Lin; Wilkens, Lynne R; Cheng, Iona

2017-10-01

Information on the role of the neighborhood environment and colorectal cancer risk is limited. We investigated the association between a comprehensive suite of possible obesogenic neighborhood attributes (socioeconomic status, population density, restaurant and retail food environments, numbers of recreational facilities and businesses, commute patterns, traffic density, and street connectivity) and colorectal cancer risk in the Multiethnic Cohort Study. Among 81,197 eligible participants living in California (35,397 males and 45,800 females), 1973 incident cases (981 males and 992 females) of invasive colorectal cancer were identified between 1993 and 2010. Separately for males and females, multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer risk overall and by racial/ethnic group (African American, Japanese American, Latino, white). In males, higher traffic density was associated with an increased risk of colorectal cancer (HR=1.29, 95% CI: 1.03-1.61, p=0.03, for quintile 5 vs. quintile 1; p-trend=0.06). While this association may be due to chance, this pattern was seen (albeit non-statistically significant) in all racial/ethnic groups except whites. There were no other significant associations between other neighborhood obesogenic attributes and colorectal cancer risk. Findings from our large racial/ethnically diverse cohort suggest neighborhood obesogenic characteristics are not strongly associated with the risk of colorectal cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Aspirin and colorectal cancer].

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Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

2018-02-01

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.

Associations of Statin Use With Colorectal Cancer Recurrence and Mortality in a Danish Cohort.

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Lash, Timothy L; Riis, Anders H; Ostenfeld, Eva B; Erichsen, Rune; Vyberg, Mogens; Ahern, Thomas P; Thorlacius-Ussing, Ole

2017-09-15

In earlier studies of the influence of hydroxymethylglutaryl-coenzyme A reductase inhibitors (also known as statins) on colorectal cancer prognosis, investigators reported a reduced rate of cancer-specific mortality. Studies of recurrence are few and small. Using data from Danish registries, we followed 21,152 patients diagnosed with stage I-III colorectal cancer from 2001 to 2011. We estimated the association between statin use in the preceding year and cancer recurrence, cancer-specific mortality, and all-cause mortality rates. We identified 5,036 recurrences, 7,084 deaths from any cause, and 4,066 deaths from colorectal cancer. After adjustment for potential confounders, statin use was not associated with recurrence (adjusted hazard ratio (aHR) = 1.01, 95% confidence interval (CI): 0.93, 1.09), but it was associated with death from colorectal cancer (aHR = 0.72, 95% CI: 0.65, 0.79) and death from any cause (aHR = 0.72, 95% CI: 0.67, 0.76). Statin use in the year preceding recurrence was associated with a reduced risk of cancer-specific mortality (aHR = 0.83, 95% CI: 0.74, 0.92) but also a reduced risk of death from any other cause (aHR = 0.78, 95% CI: 0.61, 1.00). Statin use was not associated with a reduced rate of colorectal cancer recurrence, but it was associated with a reduced rate of cancer-specific mortality, which suggests that there is no cancer-directed benefit; therefore, there is no basis to prescribe statins to colorectal cancer patients who do not have cardiovascular indications. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dietary patterns and colorectal cancer in a Japanese population: the Fukuoka Colorectal Cancer Study.

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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

2010-12-01

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.

Retrotransposition of long interspersed nucleotide element-1 is associated with colitis but not tumors in a murine colitic cancer model.

Directory of Open Access Journals (Sweden)

Takeshi Otsubo

Full Text Available Long interspersed element-1 (L1 is a transposable element that can move within the genome, potentially leading to genome diversity and modified gene function. Although L1 activity in somatic cells is normally suppressed through DNA methylation, some L1s are activated in tumors including colorectal carcinoma. However, how L1-retrotransposition (L1-RTP is involved in gastrointestinal disorders remains to be elucidated. We hypothesized that L1-RTP in somatic cells might contribute to colitis-associated cancer (CAC. To address this, we employed an experimental model of CAC using transgenic L1-reporter mice carrying a human L1-EGFP reporter gene. Mice were subjected to repeated cycles of colitis induced by administration of dextran sodium sulfate (DSS in drinking water with injection of carcinogen azoxymethane (AOM. L1-RTP levels were measured by a quantitative polymerase chain reaction targeting the newly inserted reporter EGFP in various tissues and cell types, including samples obtained by laser microdissection and cell sorting with flow cytometry. DNA methylation levels of the human L1 promoter were analyzed by bisulfite pyrosequencing. AOM+DSS-treated mice exhibited significantly higher levels of L1-RTP in whole colon tissue during the acute phase of colitis when compared with control naïve mice. L1-RTP levels in whole colon tissue were positively correlated with the histological severity of colitis and degree of neutrophil infiltration into the lamina propria (LP, but not with tumor development in the colon. L1-RTP was enriched in LP mesenchymal cells rather than epithelial cells (ECs, myeloid, or lymphoid cells. DNA methylation levels of the human L1 promoter region showed a negative correlation with L1-RTP levels. L1-RTP was absent from most tumors found in 22-week-old mice. In conclusion, we demonstrated that L1-RTP was induced in the mouse CAC mucosa in accordance with the acute inflammatory response; however, retrotransposition appears

Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency colorectal cancer care.

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Palin, R P; Devine, A T; Hicks, G; Burke, D

2018-04-01

Introduction The association between the neutrophil-lymphocyte ratio (NLR) and outcome in elective colorectal cancer surgery is well established; the relationship between NLR and the emergency colorectal cancer patient is, as yet, unexplored. This paper evaluates the predictive quality of the NLR for outcome in the emergency colorectal cancer patient. Materials and Methods A total of 187 consecutive patients who underwent emergency surgery for colorectal cancer were included in the study. NLR was calculated from the haematological tests done on admission. Receiver operating characteristic analyses were used to determine the most suitable cut-off for NLR. Outcomes were assessed by mortality at 30 and 90 days using stepwise Cox proportional hazards regression. Results An NLR cut-off of 5 was found to have the highest sensitivity and specificity. At 30 days, age and time from admission to surgery were associated with increased mortality; a high NLR was associated with an increased risk of mortality in univariate but not multivariate analysis. At 90 days, age, NLR, time from admission to surgery and nodal status were all significantly associated with increased mortality on multivariate analysis. Conclusions Pre-operative NLR is a cheap, easily performed and useful clinical tool to aid prediction of outcome in the emergency colorectal cancer patient.

Primary prevention of colorectal cancer.

Science.gov (United States)

Chan, Andrew T; Giovannucci, Edward L

2010-06-01

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.

Industrial risk factors for colorectal cancer

International Nuclear Information System (INIS)

Lashner, B.A.; Epstein, S.S.

1990-01-01

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

An apple oligogalactan potentiates the growth inhibitory effect of celecoxib on colorectal cancer.

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Li, Yuhua; Niu, Yinbo; Sun, Yang; Mei, Lin; Zhang, Bangle; Li, Qian; Liu, Li; Zhang, Rong; Chen, Jianfa; Mei, Qibing

2014-01-01

Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0-1 g/L), celecoxib (0-25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1-0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy.

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans

OpenAIRE

Sanapareddy, Nina; Legge, Ryan M; Jovov, Biljana; McCoy, Amber; Burcal, Lauren; Araujo-Perez, Felix; Randall, Thomas A; Galanko, Joseph; Benson, Andrew; Sandler, Robert S; Rawls, John F; Abdo, Zaid; Fodor, Anthony A; Keku, Temitope O

2012-01-01

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn's disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1–V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria fr...

Colorectal Cancer Prevention

Science.gov (United States)

... 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 ...

Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease

DEFF Research Database (Denmark)

Munkholm, P

2003-01-01

Although colorectal cancer (CRC), complicating ulcerative colitis and Crohn's disease, only accounts for 1-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 15% of all deaths in inflammatory bowel disease (IBD...

Colorectal Cancer Screening

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... 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 ...

Colorectal Cancer Rates by Race and Ethnicity

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... 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 ...

Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

Science.gov (United States)

Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

2015-01-01

Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

[Obesity and colorectal cancer].

Science.gov (United States)

Na, Soo-Young; Myung, Seung-Jae

2012-01-01

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.

Higher intake of carotenoid is associated with a lower risk of colorectal cancer in Chinese adults: a case-control study.

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Lu, Min-Shan; Fang, Yu-Jing; Chen, Yu-Ming; Luo, Wei-Ping; Pan, Zhi-Zhong; Zhong, Xiao; Zhang, Cai-Xia

2015-06-01

The associations between specific carotenoid intake and colorectal cancer risk remain inconsistent. The aim of this study was to examine the association between specific dietary carotenoid intake with colorectal cancer risk in Chinese adults. From July 2010 to October 2013, 845 eligible colorectal cancer cases and 845 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate logistical regression models were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CIs) of colorectal cancer risk after adjusting for various confounders. A strong inverse association was found between β-cryptoxanthin intake and colorectal cancer risk. Compared with the lowest quartile, the highest quartile intake showed a risk reduction of 77% (OR 0.23, 95% CI 0.17-0.33, P trend colorectal cancer risk. These findings were consistent across cancer site, sources of controls, and smoking status. The inverse associations between dietary α-carotene, β-cryptoxanthin, and lycopene intake and colorectal cancer risk were found in both males and females, while inverse associations between β-carotene intake and colorectal cancer risk were only observed in males. Consumption of α-carotene, β-carotene, β-cryptoxanthin, and lycopene was inversely associated with colorectal cancer risk. No significant association was found between lutein/zeaxanthin intake and colorectal cancer risk.

Nutrients, foods, and colorectal cancer prevention.

Science.gov (United States)

Song, Mingyang; Garrett, Wendy S; Chan, Andrew T

2015-05-01

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.

Coffee Consumption and the Risk of Colorectal Cancer.

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Schmit, Stephanie L; Rennert, Hedy S; Rennert, Gad; Gruber, Stephen B

2016-04-01

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.

Aberrant TET1 Methylation Closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer.

Science.gov (United States)

Ichimura, Norihisa; Shinjo, Keiko; An, Byonggu; Shimizu, Yasuhiro; Yamao, Kenji; Ohka, Fumiharu; Katsushima, Keisuke; Hatanaka, Akira; Tojo, Masayuki; Yamamoto, Eiichiro; Suzuki, Hiromu; Ueda, Minoru; Kondo, Yutaka

2015-08-01

Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer. The relationship between TET inactivation and CIMP in colorectal cancers is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) colorectal cancers. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in colorectal cancers, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of colorectal cancers as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (23/55, 42%) than CIMP-N (2/113, 2%, P CIMP-P, 16/40, 40%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P colorectal cancers. Colorectal cancers with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in colorectal cancer. ©2015 American Association for Cancer Research.

Microbial and viral pathogens in colorectal cancer.

LENUS (Irish Health Repository)

Collins, Danielle

2011-05-01

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.

Microbial and viral pathogens in colorectal cancer.

LENUS (Irish Health Repository)

Collins, Danielle

2012-02-01

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.

Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer.

Science.gov (United States)

Masoudi, Mohammad; Saadat, Iraj; Omidvari, Shahpour; Saadat, Mostafa

2011-10-01

Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.

Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

Directory of Open Access Journals (Sweden)

Ashlee B. Carter

2009-01-01

Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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Federica Marchesi

2011-12-01

Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

2011-12-28

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

International Nuclear Information System (INIS)

Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2011-01-01

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

Colorectal Cancer Chemoprevention by Mesalazine and Its Derivatives

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Carmine Stolfi

2012-01-01

Full Text Available Patients with inflammatory bowel disease (IBD face an increased lifetime risk of developing colorectal cancer (CRC. Independent factors associated with increased risk include long disease duration, extensive colonic involvement, young age at onset of IBD, severity of inflammation, primary sclerosing cholangitis, backwash ileitis, and a family history of CRC, thus emphasising the role of intestinal inflammation as an underlying mechanism. This notion is also supported by the demonstration that the use of certain drugs used to attenuate the ongoing mucosal inflammation, such as mesalazine, seems to associate with a reduced incidence of colitis-associated CRC. In the last decade, work from many laboratories has contributed to delineate the mechanisms by which mesalazine alters CRC cell behaviour. In this paper, we review the available experimental data supporting the ability of mesalazine and its derivatives to interfere with intracellular signals involved in CRC cell growth.

Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

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Trubicka, Joanna; Byrski, Tomasz; Gronwald, Jacek; Złowocka, Elżbieta; Kładny, Józef; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Kowalska, Elżbieta; Lubinski, Jan; Scott, Rodney J; Grabowska-Kłujszo, Ewa; Suchy, Janina; Masojć, Bartłomiej; Serrano-Fernandez, Pablo; Kurzawski, Grzegorz; Cybulski, Cezary; Górski, Bohdan; Huzarski, Tomasz

2010-01-01

CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations

Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

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Trubicka Joanna

2010-08-01

Full Text Available Abstract Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs, it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. Results The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Conclusion Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.

Mucosal healing in ulcerative colitis

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Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

2013-01-01

Ulcerative colitis (UC) is a colonic inflammatory condition with a substantial impact on the quality of life of affected persons. The disease carries a cumulative risk of need of colectomy of 20-30% and an estimated cumulative risk of colorectal cancer of 18% after 30 years of disease duration. W...

The Association of Perceived Provider-Patient Communication and Relationship Quality with Colorectal Cancer Screening

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Underhill, Meghan L.; Kiviniemi, Marc T.

2012-01-01

Background: Two-thirds of adults aged 50 years and older are adherent to recommendations for colorectal cancer screening. Provider-patient communication and characteristics of the patient-provider relationship may relate to screening behavior. Methods: The association of provider communication quality, relationship, and colorectal cancer screening…

Selenoprotein P in colitis-associated carcinoma

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Short, Sarah P.; Whitten-Barrett, Caitlyn; Williams, Christopher S.

2016-01-01

ABSTRACT Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine. PMID:27314080

Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial-mesenchymal transition

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Lianjie eLin

2016-01-01

Full Text Available Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC as well as colorectal cancer (CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM and dextran sodium sulfate (DSS. Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA. In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α, interleukin (IL-1β and IL-6, down-regulation of cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS, and inactivation of nuclear factor κB (NF-κB. Moreover, celastrol obviously suppressed epithelial mesenchymal transition (EMT through up-regulating E-cadherin and down-regulating N-cadherin, Vimentin and Snail. Additionally, we also demonstrated that celastrol inhibited human CRC cell proliferation and attenuated colonic xenograft tumor growth via reversing EMT. Taken together, celastrol could effectively ameliorate UC-CRC by suppressing inflammatory responses and EMT, suggesting a potential drug candidate for UC-CRC therapy.

Association of dietary insulinemic potential and colorectal cancer risk in men and women.

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Tabung, Fred K; Wang, Weike; Fung, Teresa T; Smith-Warner, Stephanie A; Keum, NaNa; Wu, Kana; Fuchs, Charles S; Hu, Frank B; Giovannucci, Edward L

2018-06-12

Insulin response may be important in colorectal cancer development. Diet modulates insulin response and may be a modifiable factor in colorectal cancer prevention. We examined associations between hyperinsulinemic diets and colorectal cancer risk with the use of an empirical dietary index for hyperinsulinemia (EDIH), a food-based index that characterizes dietary insulinemic potential on the basis of circulating C-peptide concentrations. Diet was assessed every 4 y with food-frequency questionnaires in 46,210 men (Health Professionals Follow-Up Study, 1986-2012) and 74,191 women (Nurses' Health Study, 1984-2012) to calculate EDIH scores. Multivariable-adjusted Cox regression was used to calculate HRs and 95% CIs for colorectal, proximal/distal colon, and rectal cancer risk. During 26 y of follow-up, we documented 2683 incident colorectal cancer cases. Comparing participants in the highest with those in the lowest quintiles, higher EDIH scores were associated with 33% (men: HR: 1.33; 95% CI: 1.11, 1.61; P-trend = 0.0005), 22% (women: HR: 1.22; 95% CI: 1.03, 1.45; P-trend = 0.01), and 26% (men and women: pooled HR: 1.26; 95% CI: 1.12, 1.42; P-trend <0.0001) higher risk of developing colorectal cancer. The positive associations were limited to the distal colon and rectum in men and to the distal and proximal colon in women; however, combined risk estimates were significant for all anatomic locations except for the rectum. For example, comparing participants in extreme EDIH quintiles, there was no significant association for proximal colon cancer in men (HR: 1.15; 95% CI: 0.84, 1.57; P-trend = 0.32), but the risk was elevated for distal colon (HR: 1.63; 95% CI: 1.14, 2.32; P-trend = 0.002) and rectal (HR: 1.63; 95% CI: 1.09, 2.44; P-trend = 0.01) cancer. Among women, the risk was elevated for proximal (HR: 1.28; 95% CI: 1.00, 1.63; P-trend = 0.03) and distal (HR: 1.46; 95% CI: 1.05, 2.03; P-trend = 0.03) colon cancer but not for rectal cancer (HR: 0.88; 95

Atrial fibrillation and survival in colorectal cancer

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Justin Timothy A

2004-11-01

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.

Crohn's Disease and Ulcerative Colitis: A Guide for Parents

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... can control the chronic inflammation that is a hallmark of IBD. This will help achieve long-term ... by scar tissue perforation of the intestines colorectal cancer or risk of it In ulcerative colitis, the ...

Management of colorectal cancer and diabetes

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Yao, Caroline; Nash, Guy F; Hickish, Tamas

2014-01-01

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...

Association of Calcium-Sensing Receptor (CASR rs 1801725 with Colorectal Cancer

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Fateme Rostami

2012-07-01

Full Text Available Background: Calcium induces apoptosis in intestinal epithelial cells and subsequently prevents colorectal cancer through ion calcium receptor. Calcium-sensing receptor mutation reduces the expression of this receptor, and subsequently in reduces calcium transportation. Many studies have shown that Calcium-sensing receptor gene polymorphism may increase the risk of colorectal cancer. The purpose of this study is to assess the prevalence of calcium-sensing receptor polymorphisms (rs 1801725 in Iran society and to examine the role of this polymorphism in the increased risk of colorectal cancer (CRC.Materials and Methods: The research was a case-control study. 105 patients with colorectal cancer and 105 controls were randomly studied using polymerase chain reaction and restriction fragment length polymorphism. χ2 test and software 16- SPSS were used for statistical analysis.Results: In patient samples, the frequency of the genotypes TT, GT, GG in gene CASR rs 1801725 was respectively 64.8, 32.4, and 2.9 and the frequency of this polymorphism in control samples was respectively 51.2, 45.7, and 2.9. Frequency of allele G in patient samples was 0/48 and frequency of allele T was 0.25. In addition, Frequency of allele G in control samples was 0.74 and Frequency of allele T was calculated 0.19.Conclusion: The results show that calcium-sensing receptor variant (1801725 rs is not associated with increased risk of colorectal cancer.

Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

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Kun Shang

Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice

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Wang, Chen; Wang, Zhen; Gu, Hong-Yu; Du, Xiang; Zhou, Xiao-Yan; Zheng, Chun-Lei; Chi, Ya-Yun; Mukaida, Naofumi; Li, Ying-Yi

2012-01-01

Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2–CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer. PMID:23272179

Aurora-A Expression Is Independently Associated with Chromosomal Instability in Colorectal Cancer

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Yoshifumi Baba

2009-05-01

Full Text Available AURKA (the official symbol for Aurora-A, STK15, or BTAK regulates the function of centrosomes, spindles, and kinetochores for proper mitotic progression. AURKA overexpression is observed in various cancers including colon cancer, and a link between AURKA and chromosomal instability (CIN has been proposed. However, no study has comprehensively examined AURKA expression in relation to CIN or prognosis using a large number of tumors. Using 517 colorectal cancers in two prospective cohort studies, we detected AURKA overexpression (by immunohistochemistry in 98 tumors (19%. We assessed other molecular events including loss of heterozygosity (LOH in 2p, 5q, 17q, and 18q, the CpG island methylation phenotype (CIMP, and microsatellite instability (MSI. Prognostic significance of AURKA was evaluated by Cox regression and Kaplan-Meier method. In both univariate and multivariate logistic regressions, AURKA overexpression was significantly associated with CIN (defined as the presence of LOH in any of the chromosomal segments; multivariate odds ratio, 2.97; 95% confidence interval, 1.40–6.29; P = .0045. In multivariate analysis, AURKA was associated with cyclin D1 expression (P = .010 and inversely with PIK3CA mutation (P=.014, fatty acid synthase expression (P=.028, and family history of colorectal cancer (P = .050, but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, β-catenin, or cyclooxygenase 2. AURKA was not significantly associated with clinical outcome or survival. In conclusion, AURKA overexpression is independently associated with CIN in colorectal cancer, supporting a potential role of Aurora kinase-A in colorectal carcinogenesis through genomic instability (rather than epigenomic instability.

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

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Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

2017-08-01

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

Alcohol intake and mortality among survivors of colorectal cancer: The Cancer Prevention Study II Nutrition Cohort.

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Yang, Baiyu; Gapstur, Susan M; Newton, Christina C; Jacobs, Eric J; Campbell, Peter T

2017-06-01

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.

Meat-related compounds and colorectal cancer risk by anatomical subsite.

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Miller, Paige E; Lazarus, Philip; Lesko, Samuel M; Cross, Amanda J; Sinha, Rashmi; Laio, Jason; Zhu, Jay; Harper, Gregory; Muscat, Joshua E; Hartman, Terryl J

2013-01-01

Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends cancer and pan-fried red meat and colorectal cancer were found (P-trends cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.

A novel murine model of inflammatory bowel disease and inflammation-associated colon cancer with ulcerative colitis-like features.

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Laura P Hale

Full Text Available Mutations that increase susceptibility to inflammatory bowel disease (IBD have been identified in a number of genes in both humans and mice, but the factors that govern how these mutations contribute to IBD pathogenesis and result in phenotypic presentation as ulcerative colitis (UC or Crohn disease (CD are not well understood. In this study, mice deficient in both TNF and IL-10 (T/I mice were found to spontaneously develop severe colitis soon after weaning, without the need for exogenous triggers. Colitis in T/I mice had clinical and histologic features similar to human UC, including a markedly increased risk of developing inflammation-associated colon cancer. Importantly, development of spontaneous colitis in these mice was prevented by antibiotic treatment. Consistent with the known role of Th17-driven inflammation in response to bacteria, T/I mice had elevated serumTh17-type cytokines when they developed spontaneous colitis and after systemic bacterial challenge via NSAID-induced degradation of the mucosal barrier. Although TNF production has been widely considered to be be pathogenic in IBD, these data indicate that the ability to produce normal levels of TNF actually protects against the spontaneous development of colitis in response to intestinal colonization by bacteria. The T/I mouse model will be useful for developing new rationally-based therapies to prevent and/or treat IBD and inflammation-associated colon cancer and may further provide important insights into the pathogenesis of UC in humans.

Probiotic Strain Lactobacillus casei BL23 Prevents Colitis-Associated Colorectal Cancer

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Elsa Jacouton

2017-11-01

Full Text Available The gut microbiota plays a major role in intestinal health, and an imbalance in its composition can lead to chronic gut inflammation and a predisposition to developing colorectal cancer (CRC. Currently, the use of probiotic bacteria represents an emerging alternative to treat and prevent cancer. Moreover, consumption of these beneficial bacteria may also favorably modulate the composition of the gut microbiota, which has been described in several studies to play an important role in CRC carcinogenesis. In this context, the aim of this study was to assess the protective effect of oral treatment with Lactobacillus casei BL23, a probiotic strain well known for its anti-inflammatory and anticancer properties. First, CRC was induced in C57BL6 mice by a single intraperitoneal injection with azoxymethane (8 mg/kg, followed by four courses of dextran sodium sulfate (2.5% in drinking water that were separated by an adjustable recovery period. At the time of sacrifice (day 46, tumor incidence, histological scores, and epithelial proliferation were determined in colon samples. Our results show that L. casei BL23 significantly protected mice against CRC development; specifically, L. casei BL23 treatment reduced histological scores and proliferative index values. In addition, our analysis revealed that L. casei BL23 had an immunomodulatory effect, mediated through the downregulation of the IL-22 cytokine, and an antiproliferative effect, mediated through the upregulation of caspase-7, caspase-9, and Bik. Finally, L. casei BL23 treatment tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an analysis of fecal microbiota. Altogether our results demonstrate the high potential of L. casei BL23 for the development of new, probiotic-based strategies to fight CRC.

Lack of STAT6 Attenuates Inflammation and Drives Protection against Early Steps of Colitis-Associated Colon Cancer.

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Leon-Cabrera, Sonia A; Molina-Guzman, Emmanuel; Delgado-Ramirez, Yael G; Vázquez-Sandoval, Armando; Ledesma-Soto, Yadira; Pérez-Plasencia, Carlos G; Chirino, Yolanda I; Delgado-Buenrostro, Norma L; Rodríguez-Sosa, Miriam; Vaca-Paniagua, Felipe; Ávila-Moreno, Federico; Gutierrez-Cirlos, Emma B; Arias-Romero, Luis E; Terrazas, Luis I

2017-05-01

Colitis-associated colon cancer (CAC) is one of the most common malignant neoplasms and a leading cause of death. The immunologic factors associated with CAC development are not completely understood. Signal transducer and activator of transcription 6 (STAT6) is part of an important signaling pathway for modulating intestinal immune function and homeostasis. However, the role of STAT6 in colon cancer progression is unclear. Following CAC induction in wild-type (WT) and STAT6-deficient mice (STAT6 -/- ), we found that 70% of STAT6 -/- mice were tumor-free after 8 weeks, whereas 100% of WT mice developed tumors. STAT6 -/- mice displayed fewer and smaller colorectal tumors than WT mice; this reduced tumorigenicity was associated with decreased proliferation and increased apoptosis in the colonic mucosa in the early steps of tumor progression. STAT6 -/- mice also exhibited reduced inflammation, diminished concentrations COX2 and nuclear β-catenin protein in the colon, and decreased mRNA expression of IL17A and TNFα, but increased IL10 expression when compared with WT mice. Impaired mucosal expression of CCL9, CCL25, and CXCR2 was also observed. In addition, the number of circulating CD11b + Ly6C hi CCR2 + monocytes and CD11b + Ly6C low Ly6G + granulocytes was both decreased in a STAT6-dependent manner. Finally, WT mice receiving a STAT6 inhibitor in vivo confirmed a significant reduction in tumor load as well as less intense signs of CAC. Our results demonstrate that STAT6 is critical in the early steps of CAC development for modulating inflammatory responses and controlling cell recruitment and proliferation. Thus, STAT6 may represent a promising target for CAC treatment. Cancer Immunol Res; 5(5); 385-96. ©2017 AACR . ©2017 American Association for Cancer Research.

Vitamin D, inflammation, and colorectal cancer progression

NARCIS (Netherlands)

Harten-Gerritsen, van Suzanne; Balvers, Michiel G.J.; Witkamp, Renger F.; Kampman, Ellen; Duijnhoven, van F.J.B.

2015-01-01

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

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

Science.gov (United States)

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

2017-11-13

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.

The Risk of Colorectal Cancer in Patients With Type 2 Diabetes : Associations With Treatment Stage and Obesity

NARCIS (Netherlands)

Peeters, Paul J H L; Bazelier, Marloes T; Leufkens, Hubert G M; de Vries, Frank; De Bruin, Marie L

2014-01-01

OBJECTIVE: To assess the risk of colorectal cancer associated with type 2 diabetes, as compared with a nondiabetic reference population, and to study additional associations between treatment stage and duration of obesity and colorectal cancer risk. RESEARCH DESIGN AND METHODS: We conducted an

Colorectal cancer

International Nuclear Information System (INIS)

Akiba, Suminori

1992-01-01

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.)

The Association of Cholelithiasis and Colorectal Cancer

Directory of Open Access Journals (Sweden)

C Sărăcuț

2014-02-01

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

Epigenetics and Colorectal Cancer

Science.gov (United States)

Lao, Victoria Valinluck; Grady, William M.

2012-01-01

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

Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite

Science.gov (United States)

Miller, Paige E.; Lazarus, Philip; Lesko, Samuel M.; Cross, Amanda J.; Sinha, Rashmi; Laio, Jason; Zhu, Jay; Harper, Gregory; Muscat, Joshua E.; Hartman, Terryl J.

2012-01-01

Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted. PMID:23441608

Avoiding restorative proctocolectomy for colorectal cancer in patients with ulcerative colitis based on preoperative diagnosis involving p53 immunostaining: report of a case.

Science.gov (United States)

Sada, Haruki; Shimomura, Manabu; Hinoi, Takao; Egi, Hiroyuki; Kawaguchi, Koji; Yano, Takuya; Niitsu, Hiroaki; Saitou, Yasufumi; Sawada, Hiroyuki; Miguchi, Masashi; Adachi, Tomohiro; Ohdan, Hideki

2015-03-26

The standard operation for colitic cancer in ulcerative colitis (UC) is restorative proctocolectomy; however, sporadic colorectal cancer (CRC) can coincidentally arise in patients with UC and the optimal procedure remains controversial. Therefore, it is crucial to preoperatively determine whether the CRC in UC is a sporadic or colitic cancer. We report a case of avoiding proctocolectomy for sporadic CRC in a patient with UC based on preoperative diagnosis involving p53 immunostaining. A 73-year-old man with CRC in UC had undergone sigmoid colectomy with lymphadenectomy because of the submucosal deep invasion pathologically after endoscopic mucosal resection. The cancer was diagnosed sporadic cancer preoperatively not only based on the endoscopic, clinical, and histological patterns but also that the colon epithelium was unlikely to develop dysplasia as the circumference and unaffected UC mucosa did not detect p53 protein overexpression. Recent reports have shown that the immunohistochemical detection of p53 protein overexpression can be useful for a differential diagnosis and as a predictor of dysplasia and colitic cancer. The analysis of p53 mutation status based on immunostaining of p53 protein expression in the unaffected UC mucosa can be useful for the decision regarding a surgical procedure for CRC in patients with UC.

Risks of Colorectal Cancer Screening

Science.gov (United States)

... 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 ...

Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer.

Science.gov (United States)

Bergmann, Hanna; Roth, Susanne; Pechloff, Konstanze; Kiss, Elina A; Kuhn, Sabine; Heikenwälder, Mathias; Diefenbach, Andreas; Greten, Florian R; Ruland, Jürgen

2017-08-01

Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model. Card9 -/- mice develop smaller, less proliferative and less dysplastic tumors compared to their littermates and in the regenerating mucosa we detected dramatically impaired IL-1β generation and defective IL-1β controlled IL-22 production from group 3 innate lymphoid cells. Consistent with the key role of immune-derived IL-22 in activating STAT3 signaling during normal and pathological intestinal epithelial cell (IEC) proliferation, Card9 -/- mice also exhibit impaired tumor cell intrinsic STAT3 activation. Our results imply a Card9-controlled, ILC3-mediated mechanism regulating healthy and malignant IEC proliferation and demonstrates a role of Card9-mediated innate immunity in inflammation-associated carcinogenesis. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

NARCIS (Netherlands)

Fehringer, G. (Gordon); P. Kraft (Peter); P.D.P. Pharoah (Paul); R. Eeles (Rosalind); Chatterjee, N. (Nilanjan); F.R. Schumacher (Fredrick R); J.M. Schildkraut (Joellen); S. Lindstrom (Stephen); P. Brennan (Paul); H. Bickeböller (Heike); R. Houlston (Richard); M.T. Landi (Maria Teresa); N.E. Caporaso (Neil); Risch, A. (Angela); A.A. Al Olama (Ali Amin); S.I. Berndt (Sonja); Giovannucci, E.L. (Edward L.); H. Grönberg (Henrik); Z. Kote-Jarai; Ma, J. (Jing); K.R. Muir (K.); M.J. Stampfer (Meir J.); Stevens, V.L. (Victoria L.); F. Wiklund (Fredrik); W.C. Willett (Walter C.); E.L. Goode (Ellen); Permuth, J.B. (Jennifer B.); H. Risch (Harvey); Reid, B.M. (Brett M.); Bezieau, S. (Stephane); H. Brenner (Hermann); Chan, A.T. (Andrew T.); J. Chang-Claude (Jenny); T.J. Hudson (Thomas); Kocarnik, J.K. (Jonathan K.); P. Newcomb (Polly); Schoen, R.E. (Robert E.); Slattery, M.L. (Martha L.); White, E. (Emily); M.A. Adank (Muriel); H. Ahsan (Habibul); K. Aittomäki (Kristiina); Baglietto, L. (Laura); Blomquist, C. (Carl); F. Canzian (Federico); K. Czene (Kamila); I. dos Santos Silva (Isabel); Eliassen, A.H. (A. Heather); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); M. García-Closas (Montserrat); M.M. Gaudet (Mia); Johnson, N. (Nichola); P. Hall (Per); A. Hazra (Aditi); R. Hein (Rebecca); Hofman, A. (Albert); J.L. Hopper (John); A. Irwanto (Astrid); M. Johansson (Mattias); R. Kaaks (Rudolf); M.G. Kibriya (Muhammad); P. Lichtner (Peter); J. Liu (Jianjun); E. Lund (Eiliv); Makalic, E. (Enes); A. Meindl (Alfons); B. Müller-Myhsok (B.); Muranen, T.A. (Taru A.); H. Nevanlinna (Heli); P.H.M. Peeters; J. Peto (Julian); R. Prentice (Ross); N. Rahman (Nazneen); M.-J. Sanchez (Maria-Jose); D.F. Schmidt (Daniel); R.K. Schmutzler (Rita); M.C. Southey (Melissa); Tamimi, R. (Rulla); S.P.L. Travis (Simon); C. Turnbull (Clare); Uitterlinden, A.G. (Andre G.); Z. Wang (Zhaoming); A.S. Whittemore (Alice); X.R. Yang (Xiaohong); W. Zheng (Wei); D. Buchanan (Daniel); G. Casey (Graham); G. Conti (Giario); C.K. Edlund (Christopher); S. Gallinger (Steve); R. Haile (Robert); M. Jenkins (Mark); Marchand, L. (Loïcle); Li, L. (Li); N.M. Lindor (Noralane); Schmit, S.L. (Stephanie L.); S.N. Thibodeau (Stephen); M.O. Woods (Michael); T. Rafnar (Thorunn); J. Gudmundsson (Julius); S.N. Stacey (Simon); Stefansson, K. (Kari); P. Sulem (Patrick); Chen, Y.A. (Y. Ann); J.P. Tyrer (Jonathan); Christiani, D.C. (David C.); Wei, Y. (Yongyue); H. Shen (Hongbing); Z. Hu (Zhibin); X.-O. Shu (Xiao-Ou); Shiraishi, K. (Kouya); A. Takahashi (Atsushi); Y. Bossé (Yohan); M. Obeidat (Ma'en); D.C. Nickle (David); W. Timens (Wim); M. Freedman (Matthew); Li, Q. (Qiyuan); D. Seminara (Daniela); S.J. Chanock (Stephen); Gong, J. (Jian); U. Peters (Ulrike); S.B. Gruber (Stephen); Amos, C.I. (Christopher I.); T.A. Sellers (Thomas A.); D.F. Easton (Douglas F.); D. Hunter (David); C.A. Haiman (Christopher A.); B.E. Henderson (Brian); R.J. Hung (Rayjean)

2016-01-01

textabstractIdentifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851

6 Common Cancers - Colorectal Cancer

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... 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 ( ...

Exploring Differences in the Aspirin-Colorectal Cancer Association by Sex and Race/Ethnicity: The Multiethnic Cohort Study.

Science.gov (United States)

Park, Song-Yi; Wilkens, Lynne R; Kolonel, Laurence N; Monroe, Kristine R; Haiman, Christopher A; Marchand, Loïc Le

2017-02-01

Evidence has accumulated that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer. We tested whether the inverse associations between NSAIDs and colorectal cancer is similarly observed across sexes and five racial/ethnic groups (Japanese, Latino, African American, Native Hawaiian, and white) in the Multiethnic Cohort (MEC) Study. During a mean follow-up of 16.1 years, we identified 4,882 invasive incident colorectal cancer cases among 183,199 eligible participants. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). Use of aspirin and other NSAIDs was associated with a lower incidence of colorectal cancer in men (HR = 0.77; 95% CI, 0.69-0.86 for current vs. never users of aspirin) but not in women (P interaction = 0.005). Among male current users, a reduced risk was observed with ≥6 years of aspirin or total NSAID use. The inverse association with current NSAID use in men was observed in all racial/ethnic groups, except for Native Hawaiians, and was stronger in whites. Our findings suggest that the benefit of NSAIDs for colorectal cancer may be strongest for white men and generalizes to African American, Japanese, and Latino, but not to Native Hawaiian men. The lack of inverse association observed in women and Native Hawaiian men in the MEC should be interpreted with caution. As only very few ethnic/racial groups are likely to be represented in trials of NSAIDs and colorectal cancer, it is important to conduct prospective observational studies in various populations to test the generalizability of their results. Cancer Epidemiol Biomarkers Prev; 26(2); 162-9. ©2016 AACR. ©2016 American Association for Cancer Research.

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

Science.gov (United States)

Liang, Xia; Zhang, Yong-jing; Liu, Bing; Ni, Qin; Jin, Ming-juan; Ma, Xin-yuan; Yao, Kai-yan; Li, Qi-long; Chen, Kun

2009-06-01

To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

Obesity and colorectal cancer risk

International Nuclear Information System (INIS)

Hano Garcia, Olga Marina; Wood Rodriguez, Lisette; Villa Jimenez, Oscar Manuel

2011-01-01

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

Is adherence to diet, physical activity, and body weight cancer prevention recommendations associated with colorectal cancer incidence in African American women?

Science.gov (United States)

Nomura, Sarah J O; Dash, Chiranjeev; Rosenberg, Lynn; Yu, Jeffrey; Palmer, Julie R; Adams-Campbell, Lucile L

2016-07-01

The purpose of this study was to evaluate whether adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with colorectal cancer incidence in the Black Women's Health Study (BWHS). In this ongoing prospective cohort of African American women (analytic cohort n = 49,103), 354 incident colorectal cancers were diagnosed between baseline (1995) and 2011. Adherence scores for seven WCRF/AICR recommendations (adherent = 1 point, non-adherent level 1 = 0.5 points, non-adherent level 2 = 0 points) were created using questionnaire data and summed to an overall adherence score (maximum = 7). Recommendation adherence and colorectal cancer incidence were evaluated using baseline and time-varying data in Cox regression models. At baseline, 8.5 % of women adhered >4 recommendations. In time-varying analyses, the HR was 0.98 (95 % CI 0.84-1.15) per 0.5 point higher score and 0.51 (95 % CI 0.23-1.10) for adherence to >4 compared to <3 recommendations. Adherence to individual recommendations was not associated with colorectal cancer risk. Results were similar in models that considered baseline exposures only. Adherence to cancer prevention recommendations was low and not associated with colorectal cancer risk among women in the BWHS. Research in diverse populations is essential to evaluate the validity of existing recommendations, and assess whether there are alternative recommendations that are more beneficial for cancer prevention in specific populations.

Association study of genetic variants in estrogen metabolic pathway genes and colorectal cancer risk and survival.

Science.gov (United States)

Li, Shuwei; Xie, Lisheng; Du, Mulong; Xu, Kaili; Zhu, Lingjun; Chu, Haiyan; Chen, Jinfei; Wang, Meilin; Zhang, Zhengdong; Gu, Dongying

2018-05-16

Although studies have investigated the association of genetic variants and the abnormal expression of estrogen-related genes with colorectal cancer risk, the evidence remains inconsistent. We clarified the relationship of genetic variants in estrogen metabolic pathway genes with colorectal cancer risk and survival. A case-control study was performed to assess the association of single-nucleotide polymorphisms (SNPs) in ten candidate genes with colorectal cancer risk in a Chinese population. A logistic regression model and Cox regression model were used to calculate SNP effects on colorectal cancer susceptibility and survival, respectively. Expression quantitative trait loci (eQTL) analysis was conducted using the Genotype-Tissue Expression (GTEx) project dataset. The sequence kernel association test (SKAT) was used to perform gene-set analysis. Colorectal cancer risk and rs3760806 in SULT2B1 were significantly associated in both genders [male: OR = 1.38 (1.15-1.66); female: OR = 1.38 (1.13-1.68)]. Two SNPs in SULT1E1 were related to progression-free survival (PFS) [rs1238574: HR = 1.24 (1.02-1.50), P = 2.79 × 10 -2 ; rs3822172: HR = 1.30 (1.07-1.57), P = 8.44 × 10 -3 ] and overall survival (OS) [rs1238574: HR = 1.51 (1.16-1.97), P = 2.30 × 10 -3 ; rs3822172: HR = 1.53 (1.67-2.00), P = 2.03 × 10 -3 ]. Moreover, rs3760806 was an eQTL for SULT2B1 in colon samples (transverse: P = 3.6 × 10 -3 ; sigmoid: P = 1.0 × 10 -3 ). SULT2B1 expression was significantly higher in colorectal tumor tissues than in normal tissues in the Cancer Genome Atlas (TCGA) database (P colorectal cancer susceptibility and survival.

Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Science.gov (United States)

Symer, Matthew M; Wong, Natalie Z; Abelson, Jonathan S; Milsom, Jeffrey W; Yeo, Heather L

2018-06-01

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.

The risk of colorectal cancer in patients with type 2 diabetes

DEFF Research Database (Denmark)

Peeters, Paul J H L; Bazelier, Marloes T; Leufkens, Hubert G M

2015-01-01

, 2,759 cases of colorectal cancer were observed among the diabetic study population. Type 2 diabetes was associated with a 1.3-fold increased risk of colorectal cancer (HR 1.26 [95% CI 1.18-1.33]). Among diabetic patients, no association was found with treatment stages. A trend of increased......OBJECTIVE: To assess the risk of colorectal cancer associated with type 2 diabetes, as compared with a nondiabetic reference population, and to study additional associations between treatment stage and duration of obesity and colorectal cancer risk. RESEARCH DESIGN AND METHODS: We conducted...... hazards models were used to derive adjusted hazard ratios (HRs) for colorectal cancer associated with type 2 diabetes. Within the diabetic cohort, associations of colorectal cancer with treatment stages and duration of obesity (BMI ≥30 kg/m(2)) were studied. RESULTS: After a median follow-up of 4.5 years...

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

NARCIS (Netherlands)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindstrom, Sara; Brennan, Paul; Bickeboller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Gronberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomaki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Timens, Wim

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

NARCIS (Netherlands)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Buchanan, Daniel D.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Gallinger, Steven; Haile, Robert W.; Jenkins, Mark; Marchand, Loïcle; Li, Li; Lindor, Noralene M.; Schmit, Stephanie L.; Thibodeau, Stephen N.; Woods, Michael O.; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820

Colorectal Cancer

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... 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 ...

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study).

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Caan, Bette J; Meyerhardt, Jeffrey A; Kroenke, Candyce H; Alexeeff, Stacey; Xiao, Jingjie; Weltzien, Erin; Feliciano, Elizabeth Cespedes; Castillo, Adrienne L; Quesenberry, Charles P; Kwan, Marilyn L; Prado, Carla M

2017-07-01

Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival. Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM). Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and cancer, and should, along with adiposity be a standard oncological marker. Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Genetic variant rs7758229 in 6q26-q27 is not associated with colorectal cancer risk in a Chinese population.

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Lingjun Zhu

Full Text Available BACKGROUND: A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population. METHODS: We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations. RESULTS: No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI = 0.84-1.09, P = 0.463. Similar results were observed in the stratification of tumor location (OR = 0.94, 95%CI = 0.80-1.11, P = 0.481 for colon cancer, and OR = 0.96, 95%CI = 0.82-1.13, P = 0.621 for rectum cancer. CONCLUSIONS: Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population.

GSTT2 promoter polymorphisms and colorectal cancer risk

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Ahn Sun-A

2007-01-01

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.

HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis.

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Chen, Weidong; Zhao, Hua; Li, Tiegang; Yao, Hongliang

2013-08-01

The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

Higher freshwater fish and sea fish intake is inversely associated with colorectal cancer risk among Chinese population: a case-control study.

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Xu, Ming; Fang, Yu-Jing; Chen, Yu-Ming; Lu, Min-Shan; Pan, Zhi-Zhong; Yan, Bo; Zhong, Xiao; Zhang, Cai-Xia

2015-08-12

The association between specific fish intake and colorectal cancer risk remains controversial. This study aimed to examine the association between specific fish intake and colorectal cancer risk in Chinese population in a large case control study. During July 2010 to November 2014, 1189 eligible colorectal cancer cases and 1189 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate logistical regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) after adjusting for various confounders. A strong inverse association was found between freshwater fish intake and colorectal cancer risk. Compared with the lowest quartile, the highest quartile intake showed a risk reduction of 53% (OR 0.47, 95% CI = 0.36-0.60, Ptrend colorectal cancer risk. These results indicate that higher consumption of freshwater fish, sea fish and fresh fish is associated with a lower risk of colorectal caner.

Genetic Mechanisms of Immune Evasion in Colorectal Cancer.

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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

2018-06-01

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.

Nutritional status assessment in colorectal cancer patients

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Joana Pedro Lopes; Paula Manuela de Castro Cardoso Pereira; Ana Filipa dos Reis Baltazar Vicente; Alexandra Bernardo; María Fernanda de Mesquita

2013-01-01

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...

Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

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Yamaguchi, Tatsuro; Furukawa, Yoichi; Nakamura, Yusuke; Matsubara, Nagahide; Ishikawa, Hideki; Arai, Masami; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Moriya, Yoshihiro; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

2015-02-01

The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Underpinning the repurposing of anthracyclines towards colorectal cancer

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Nygård, Sune Boris; Christensen, Ib Jarle; Smith, David Hersi

2013-01-01

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...

Endoscopic, epidemiologic and clinic characterization of the colorectal cancer in geriatric patients

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Umpierrez Garcia, Ibis; Herrera Hernandez Norma; Hernandez Ortega, Ania

2009-01-01

The colorectal cancer is a serious health problem because of its high incidence. In Cuba, this disease is the fourth neoplasm in order of frequency with a rate of 17.1 per 100 000 inhabitants. With the objective of determining the precocious diagnosis of this complaint we carried out a prospective, longitudinal and descriptive study among geriatric patients with colorectal disease assisting to consultation at the policlinic 'Carlos Verdugo' of Matanzas in the period from January 2006 to December 2007. The studied parameters were age, genre, risk facts, presentation forms, localization, and endoscopic diagnosis of the disease. The results showed predominance of female sex (52,1 %), in ages from 60 to 69 years old (59.3 %), predominating risk facts like familiar antecedents (13,5 %), idiopathic ulcerative colitis (8.1 %), and an inadequate diet (35.1 %). The most used diagnostic method was colonoscopy (18 patients), with predominance of the rectosigmoidal cancer (15 cases), being the polypoid one the most common endoscopic kind (13 %). We concluded that generally there is not a precocious diagnosis of the colorectal cancer among geriatric patients, leading to a decrease of the healing possibilities and surviving of these patients

Two cases of colorectal cancer developed more than 30 years after pelvic radiation therapy

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Minami, Mituaki; Aoki, Youzou; Uesaka, Kazunobu; Enomoto, Katuhiko; Shimamoto, Tetuya; Hirabayashi, Naoki [Hashimoto Municipal Hospital, Wakayama (Japan)

2000-03-01

We experienced two cases of advanced colorectal cancer developed after radiation therapy. One case was a 66-year old female who had received irradiation for her uterine cancer 35 years before. She was treated for a radiation colitis and a radiation dermatitis 6 years ago. Sigmoid colon cancer was pointed out by barium enema and colonoscopy, and Hartmann's operation was performed. The other case was a 68-year old man who had received irradiation for left malignant orchionous 30 years before. He had the radiation dermatitis in both inguinal region, and had received skin graft for the left inguinal dermatitis. He complained of anal bleeding, and rectal cancer was found out by the colonoscopy. Low anterior resection was performed. Their pathological findings showed mucinous adenocarcinoma. In a review of the Japanese literature, colorectal cancers developed more than 30 years after pelvic radiation therapy have been reported in only 8 cases including these two cases. (author)

Two cases of colorectal cancer developed more than 30 years after pelvic radiation therapy

International Nuclear Information System (INIS)

Minami, Mituaki; Aoki, Youzou; Uesaka, Kazunobu; Enomoto, Katuhiko; Shimamoto, Tetuya; Hirabayashi, Naoki

2000-01-01

We experienced two cases of advanced colorectal cancer developed after radiation therapy. One case was a 66-year old female who had received irradiation for her uterine cancer 35 years before. She was treated for a radiation colitis and a radiation dermatitis 6 years ago. Sigmoid colon cancer was pointed out by barium enema and colonoscopy, and Hartmann's operation was performed. The other case was a 68-year old man who had received irradiation for left malignant orchionous 30 years before. He had the radiation dermatitis in both inguinal region, and had received skin graft for the left inguinal dermatitis. He complained of anal bleeding, and rectal cancer was found out by the colonoscopy. Low anterior resection was performed. Their pathological findings showed mucinous adenocarcinoma. In a review of the Japanese literature, colorectal cancers developed more than 30 years after pelvic radiation therapy have been reported in only 8 cases including these two cases. (author)

Management of colorectal cancer and diabetes.

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Yao, Caroline; Nash, Guy F; Hickish, Tamas

2014-03-01

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.

EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer

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Boye, K; Nesland, J M; Sandstad, B; Haugland Haugen, M; Mælandsmo, G M; Flatmark, K

2012-01-01

Background: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. Methods: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. Results: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. Conclusion: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy. PMID:22782346

Nutrients, Foods, and Colorectal Cancer Prevention

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Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

2015-01-01

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...

Get Tested for Colorectal Cancer

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... 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 ...

Environmental Factors and Colorectal Tumor Risk in Individuals With Hereditary Nonpolyposis Colorectal Cancer

NARCIS (Netherlands)

Diergaarde, B.; Braam, H.; Vasen, H.F.; Nagengast, F.M.; Muijen, van G.N.P.; Kok, F.J.; Kampman, E.

2007-01-01

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

An innately dangerous balancing act: intestinal homeostasis, inflammation, and colitis-associated cancer

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2010-01-01

Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses to the intestinal microbiota, and by chronic intestinal inflammation. Several recent studies demonstrate the importance of innate microbial recognition by immune and nonimmune cells in the gut. Paradoxically, either diminished or exacerbated innate immune signaling may trigger the breakdown of intestinal homeostasis, leading to IBD and colitis-associated cancer (CAC). This dichotomy may reflect divergent functional roles for immune sensing in intestinal epithelial cells and leukocytes, which may vary with distinct disease mechanisms. PMID:20679404

Associations of self-reported sleep duration and snoring with colorectal cancer risk in men and women.

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Zhang, Xuehong; Giovannucci, Edward L; Wu, Kana; Gao, Xiang; Hu, Frank; Ogino, Shuji; Schernhammer, Eva S; Fuchs, Charles S; Redline, Susan; Willett, Walter C; Ma, Jing

2013-05-01

We assessed the relationship between sleep duration, snoring and colorectal cancer risk. Prospective cohort studies. United States. A total of 30,121 men aged 41 to 79 years in the Health Professionals Follow-up Study and 76,368 women aged 40 to 73 years in the Nurses' Health Study. None. We queried information on sleep duration and snoring in 1986/87. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95% CIs). We documented 1,973 incident colorectal cancer cases (709 men and 1,264 women) over a 22-year follow-up period. Compared to sleep an average 7 h, ≥ 9 h of sleep was significantly associated with a higher risk of colorectal cancer among men (HR = 1.35, 95% CI: 1.00, 1.82), and to a lesser degree, among women (HR = 1.11, 95% CI: 0.85, 1.44). The risk associated with longer sleep was restricted to individuals who regularly snored (men: HR = 1.80, 95% CI: 1.14, 2.84; women: HR = 2.32, 95% CI: 1.24, 4.36) and to overweight individuals (i.e., BMI ≥ 25 kg/m2) (men: HR = 1.52, 95% CI: 1.04, 2.21; women: HR = 1.37, 95% CI: 0.97, 1.94). Short sleep duration (≤ 5 h) was not associated with an increased risk of colorectal cancer in the entire sample or in subgroups stratified by snoring or BMI. Longer sleep duration was associated with an increased risk of developing colorectal cancer among individuals who were overweight or snored regularly. This observation raises the possibility that sleep apnea and its attendant intermittent hypoxemia may contribute to cancer risk.

Serum biomarkers of habitual coffee consumption may provide insight into the mechanism underlying the association between coffee consumption and colorectal cancer.

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Guertin, Kristin A; Loftfield, Erikka; Boca, Simina M; Sampson, Joshua N; Moore, Steven C; Xiao, Qian; Huang, Wen-Yi; Xiong, Xiaoqin; Freedman, Neal D; Cross, Amanda J; Sinha, Rashmi

2015-05-01

Coffee intake may be inversely associated with colorectal cancer; however, previous studies have been inconsistent. Serum coffee metabolites are integrated exposure measures that may clarify associations with cancer and elucidate underlying mechanisms. Our aims were 2-fold as follows: 1) to identify serum metabolites associated with coffee intake and 2) to examine these metabolites in relation to colorectal cancer. In a nested case-control study of 251 colorectal cancer cases and 247 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we conducted untargeted metabolomics analyses of baseline serum by using ultrahigh-performance liquid-phase chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Usual coffee intake was self-reported in a food-frequency questionnaire. We used partial Pearson correlations and linear regression to identify serum metabolites associated with coffee intake and conditional logistic regression to evaluate associations between coffee metabolites and colorectal cancer. After Bonferroni correction for multiple comparisons (P = 0.05 ÷ 657 metabolites), 29 serum metabolites were positively correlated with coffee intake (partial correlation coefficients: 0.18-0.61; P 0.40) included trigonelline (N'-methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8 metabolites were directly related to caffeine metabolism, and 3 of these metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95% CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear trend = 0.027), were inversely associated with colorectal cancer. Serum metabolites can distinguish coffee drinkers from nondrinkers; some caffeine-related metabolites were inversely associated with colorectal

Serum YKL-40 in risk assessment for colorectal cancer

DEFF Research Database (Denmark)

Johansen, Julia Sidenius; Christensen, Ib Jarle; Jørgensen, Lars Nannestad

2015-01-01

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...

Associations of colorectal cancer incidence with nutrient and food group intakes in korean adults: a case-control study.

Science.gov (United States)

Chun, Yu Jeong; Sohn, Seung-Kook; Song, Hye Kyung; Lee, Song Mi; Youn, Young Hoon; Lee, Seungmin; Park, Hyojin

2015-04-01

This study aimed to examine the associations between intakes of various nutrients and food groups and colorectal cancer risk in a case-control study among Koreans aged 20 to 80 years. A total of 150 new cases and 116 controls were recruited with subjects' informed consent. Dietary data were collected using the food frequency questionnaire developed and validated by the Korea Centers for Disease Control and Prevention. Multivariate logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for colorectal cancer incidence. High intakes of total lipid (ORT3 vs T1 = 4.15, 95% CI: 1.33-12.96, p for trend = 0.034), saturated fatty acid (ORT3 vs T1 = 2.96, 95% CI: 1.24-7.04, p for trend = 0.016) and monounsaturated fatty acid (ORT3 vs T1 = 3.04, 95% CI: 1.23-7.54, p for trend = 0.018) were significantly associated with increased incidence of colorectal cancer. High dietary fiber (ORT3 vs T1 = 0.22, 95% CI: 0.08-0.56, p for trend = 0.002) and vitamin C (ORT3 vs T1 = 0.38, 95% CI: 0.14-1.05, p for trend = 0.021) intakes were significantly associated with reduced colorectal cancer incidence. From the food group analysis, bread (ORT3 vs T1 = 2.26, 95% CI: 0.96-5.33, p for trend = 0.031), red meat (ORT3 vs T1 = 7.33, 95% CI: 2.98-18.06, p for trend colorectal cancer risk. On the other hand, high intake of traditional rice cake (ORT3 vs T1 = 0.35, 95% CI: 0.14-0.86, p for trend = 0.024) was linked with lower colorectal cancer incidence. In conclusion, eating a diet high in total lipid, saturated fatty acids and monounsaturated fatty acids is associated with higher incidence of colorectal cancer, whereas a diet high in dietary fiber and vitamin C was found to lower the incidence in Korean adults. Interestingly high traditional rice cake consumption is associated inversely with colorectal cancer incidence, warranting a future study.

Red wine consumption not associated with reduced risk of colorectal cancer.

Science.gov (United States)

Chao, Chun; Haque, Reina; Caan, Bette J; Poon, Kwun-Yee T; Tseng, Hung-Fu; Quinn, Virginia P

2010-01-01

Red wine contains polyphenol antioxidants that inhibit colorectal cancer (CRC) development in animal studies. We investigated the effect of red wine intake on risk of CRC in the California Men's Health Study (CMHS). CMHS is a prospective, multiethnic cohort of middle-aged men who were members of the Kaiser Permanente (KP) California Health Plans and completed study questionnaires between 2002-2003. Incident CRC were identified from the health plan cancer registries through the end of 2007 (n = 287). To properly account for potential confounding by previous endoscopy screening, we restricted the primary analyses to CMHS men continuously enrolled in KP between 1998-2002 (n = 43,483 and CRC = 176). We used multivariable Cox regression to adjust for important confounders. We did not find an inverse association between moderate red wine intake and risk of CRC. The hazard ratio for consuming >/=1 drink/day (average = 2 drinks/day) was 1.16, 95% confidence intervals 0.56-2.40. There was no linear dose-response. The lack of clear association for red wine intake was consistently observed when we stratified the analyses by CRC stage at diagnosis and cancer site (colon or rectum). Moderate red wine consumption was not associated with reduced risk of colorectal cancer in this population of middle-aged men.

Colorectal cancer associated with abdominal aortic aneurysm: results of EVAR followed by colectomy.

Science.gov (United States)

Illuminati, Giulio; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco

2013-01-01

The association of colorectal cancer and abdominal aortic aneurysm (AAA) is infrequent but poses special problems of priority of treatment under elective circumstances. The purpose of this study was to retrospectively evaluate the outcome of 16 consecutive patients undergoing endovascular aneurysm repair (EVAR) followed by colectomy. Operative mortality was nil. Operative morbidity included two transient rise of serum creatinine level and one extraperitoneal anastomotic leakage which evolved favourably with conservative treatment. EVAR allowed a very short delay of treatment of colorectal cancer after aneurysm repair, minimizing operative complications.

Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer.

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Miller, Paige E; Cross, Amanda J; Subar, Amy F; Krebs-Smith, Susan M; Park, Yikyung; Powell-Wiley, Tiffany; Hollenbeck, Albert; Reedy, Jill

2013-09-01

Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. We compared 4 established DASH indexes and examined associations with colorectal cancer. Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results.

No higher risk for colorectal cancer in atrophic gastritis-related hypergastrinemia.

Science.gov (United States)

Lahner, Edith; Sbrozzi-Vanni, Andrea; Vannella, Lucy; Corleto, Vito Domenico; Di Giulio, Emilio; Delle Fave, Gianfranco; Annibale, Bruno

2012-09-01

Atrophic gastritis of the corporal mucosa is a frequent cause of hypergastrinemia. Hypergastrinemia is implicated in colorectal cancer development. To assess whether hypergastrinemic atrophic gastritis is associated with a higher risk of neoplastic colorectal lesions. Among 441 hypergastrinemic atrophic gastritis patients, 160 who were aged >40 and underwent colonoscopy for anaemia, diarrhoea or colorectal cancer-screening were retrospectively selected. Each patient was age- and gender-matched with a normogastrinemic control with healthy stomach. Controls had colonoscopy, gastroscopy with biopsies and gastrin assessment. 160 hypergastrinemic atrophic gastritis patients and 160 controls were included. 28 atrophic gastritis patients and 36 controls had neoplastic colorectal lesions (p=0.33). Patients and controls did not differ for frequency of colorectal adenomas (10.6% vs. 13.1%, p=0.60) or cancer (6.9% vs. 9.4%, p=0.54). Hypergastrinemic atrophic gastritis was not associated with a higher probability of developing colorectal cancer (OR 1.03, 95% CI 0.34-3.16). Age >50 years (OR 3.86) but not hypergastrinemia (OR 0.61) was associated with colorectal cancer. Hypergastrinemic atrophic gastritis is not associated with higher risk for colorectal cancer. Atrophic gastritis-related hypergastrinemia is not associated with an increased risk of neoplastic colorectal lesions. Closer surveillance of colonic neoplasia in atrophic gastritis patients seems not appropriate. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The Quebec Association of Gastroenterology Position Paper on Colorectal Cancer Screening - 2003

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AN Barkun

2004-01-01

Full Text Available Colorectal cancer is a leading cause of death and the third most common cancer in Canada. Evidence suggests that screening can reduce mortality rates and the cost effectiveness of a program compares favourably with initiatives for breast and cervical cancer. The objectives of the Association des gastro-entérologues du Québec Task Force were to determine the need for a policy on screening for colorectal cancer in Quebec, to evaluate the testing methods available and to propose one or more of these alternatives as part of a formal screening program, if indicated. Fecal occult blood testing (FOBT, endoscopy (including sigmoidoscopy and colonoscopy, barium enema and virtual colonoscopy were considered. Although most clinical efficacy data are available for FOBT and sigmoidoscopy, there are limitations to programs based on these strategies. FOBT has a high false positive rate and a low detection yield, and even a combination of these strategies will miss 24% of cancers. Colonoscopy is the best strategy to both detect and remove polyps and to diagnose colorectal cancer, with double contrast barium enema also being a sensitive detection method. The Task Force recommended the establishment, in Quebec, of a screening program with five- to 10-yearly double contrast barium enema or 10-yearly colonoscopy for individuals aged 50 years or older at low risk. The program should include outcome monitoring, public and professional education to increase awareness and promote compliance, and central coordination with other provincial programs. The program should be evaluated; specific billing codes for screening for colorectal cancer would help facilitate this. Formal feasibility, effectiveness and cost-effectiveness studies in Quebec are now warranted.

Examining patterns of association with defensive information processing about colorectal cancer screening.

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McQueen, Amy; Swank, Paul R; Vernon, Sally W

2014-11-01

To reduce negative psychological affect from information or behavior that is inconsistent with one's positive self-concept, individuals use a variety of defensive strategies. It is unknown whether correlates differ across defenses. We examined correlates of four levels of defensive information processing about colorectal cancer screening. Cross-sectional surveys were completed by a convenience sample of 287 adults aged 50-75 years. Defenses measures were more consistently associated with individual differences (especially avoidant coping styles); however, situational variables involving health-care providers also were important. Future research should examine changes in defenses after risk communication and their relative impact on colorectal cancer screening. © The Author(s) 2013.

Dietary patterns and colorectal cancer risk: a meta-analysis.

Science.gov (United States)

Feng, Yu-Liang; Shu, Long; Zheng, Pei-Fen; Zhang, Xiao-Yan; Si, Cai-Juan; Yu, Xiao-Long; Gao, Wei; Zhang, Lun

2017-05-01

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.

Clinical Outcomes of Colorectal Cancer in Kenya

African Journals Online (AJOL)

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.

Preliminary screening of the radiosensitivity-associated genes on colorectal cancer

International Nuclear Information System (INIS)

Xing Chungen; Yang Xiaodong; Zhou Liying; Wu Yongyou; Jiang Yinfen; Dai Hong; Lv Xiaodong; Gong Wei

2007-01-01

The screening of radiosensitive genes of human colorectal cancer was made by gene chip. Two human colorectal cancer cell lines LOVO and SW480 were cultivated and the total RNA was extracted from at least lxl0 7 cells. Then the gene expression profiling was performed by HG-U133 Plus 2.0 Array and the difference of gene expression has been analyzed. The results shows that there are 16882 genes expressed in LOVO cell and 17114 genes expressed in SW480 cell through gene expression profiling. It has been found that the genes with 2-fold expressed differentially include 908 genes up-regulated and 1312 genes down-regulated. The same genes, such as Fas and NFkB which is up-regulated, Caspas6, and RAD21 which is down-regulated, have been proved to be related to radiosensitivity. The genes with high expression level including CEACAM5, THBS1, SERPINE2, ARL7, HPGD in LOVO cell may also be related to the radiosensitivity. And the genes with high expression level including SCD, NQ01, LYZ, KRT20, ATP1B1 in SW480 cell may be related to the radioresistance of human colorectal cancer. It could be concluded that the radiosensitivity of colorectal cancer can be reflected from gene and protein expression level. And gene expression profiling is a fast and sensitive tool to predict the radiosensitivity and screen radiosensitive genes of colorectal cancer. (authors)

Microbiota Composition, HSP70 and Caspase-3 Expression as Marker for Colorectal Cancer Patients in Aceh, Indonesia

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Fauzi Yusuf

2017-02-01

Full Text Available Aim: to investigate the relationship between microbiota composition with HSP70 and Caspase-3 expressions in colon tissue as an initial study to develop the candidate for early detection of colorectal cancer for Indonesian patients. Methods: this is a cross-sectional study on 32 patients undergoing colonoscopy; 16 patients of colorectal cancer (CRC while the other 16 patients are not (colitis and internal hemorrhoid. The composition of microbiota in stool samples was examined using 16S rRNA Denaturing Gradient Gel Electrophoresis (DDGE while expression of HSP70 was examined by immunohistochemistry and Caspase-3 by using Haematoxylin-Eosin(HE staining to determine the morphological changes in colon tissue. Results: analysis of PCR-DDGE shows a different composition of microbiota between patients with CRC and non-CRC. All CRC patients showed disappearance of dominant band from Bifidobacterium groups. Histological observation based on Inter Class Correlation (ICC test from all slide showed a high scores (5.2-9.2 in CRC patients and low scores (1.7-2.4 in non-CRC patients. HSP70 expression was increased significantly in CRC patients with the highest percentage of 84%, while expression of caspase-3 decreased with the highest percentage of 21%. Statistical analysis showed that the incidence of colorectal cancer was associated with the expression of HSP 70 (p<0.001, and Caspase 3 (p<0.001. Conclusion: bifidobacterium is an important indicator for colorectal cancer patients that show disappearance of dominant band, while expression of HSP70 increased and the Caspase-3 expression decreased significantly.

Associations between lifestyles and neutrophil-lymphocyte and platelet-lymphocyte ratios in colorectal cancer.

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Hong, Chuyuan; Wei, Yisheng; Jiang, Jianxin; Zhao, Chuxiong; Liang, Guojian; Wang, Guoqiang; Yang, Hui

2014-06-01

To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer. In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model. The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer. © 2013 Wiley Publishing Asia Pty Ltd.

Diet index-based and empirically derived dietary patterns are associated with colorectal cancer risk.

Science.gov (United States)

Miller, Paige E; Lazarus, Philip; Lesko, Samuel M; Muscat, Joshua E; Harper, Gregory; Cross, Amanda J; Sinha, Rashmi; Ryczak, Karen; Escobar, Gladys; Mauger, David T; Hartman, Terryl J

2010-07-01

Previous studies have derived patterns by measuring compliance with preestablished dietary guidance or empirical methods, such as principal components analysis (PCA). Our objective was to examine colorectal cancer risk associated with patterns identified by both methods. The study included 431 incident colorectal cancer cases (225 men, 206 women) and 726 healthy controls (330 men, 396 women) participating in a population-based, case-control study. PCA identified sex-specific dietary patterns and the Healthy Eating Index-2005 (HEI-05) assessed adherence to the 2005 Dietary Guidelines for Americans. A fruits and vegetables pattern and a meat, potatoes, and refined grains pattern were identified among men and women; a third pattern (alcohol and sweetened beverages) was identified in men. The fruits and vegetables pattern was inversely associated with risk among men [odds ratio (OR) = 0.38, 95% CI = 0.21-0.69 for the highest compared with the lowest quartile] and women (OR = 0.35, 95% CI = 0.19-0.65). The meat, potatoes, and refined grains pattern was positively associated with risk in women (OR = 2.20, 95% CI = 1.08-4.50) and there was a suggestion of a positive association among men (OR = 1.56, 95% CI = 0.84-2.90; P-trend = 0.070). Men and women with greater HEI-05 scores had a significantly reduced risk of colorectal cancer (OR = 0.56, 95% CI = 0.31-0.99; OR = 0.44, 95% CI = 0.24-0.77, respectively). Following the Dietary Guidelines or a dietary pattern lower in meat, potatoes, high fat, and refined foods and higher in fruits and vegetables may reduce colorectal cancer risk.

Higher freshwater fish and sea fish intake is inversely associated with colorectal cancer risk among Chinese population: a case-control study

OpenAIRE

Xu, Ming; Fang, Yu-Jing; Chen, Yu-Ming; Lu, Min-Shan; Pan, Zhi-Zhong; Yan, Bo; Zhong, Xiao; Zhang, Cai-Xia

2015-01-01

The association between specific fish intake and colorectal cancer risk remains controversial. This study aimed to examine the association between specific fish intake and colorectal cancer risk in Chinese population in a large case control study. During July 2010 to November 2014, 1189 eligible colorectal cancer cases and 1189 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate log...

An apple oligogalactan enhances the growth inhibitory effect of 5-fluorouracil on colorectal cancer.

Science.gov (United States)

Li, Yuhua; Fan, Lei; Niu, Yinbo; Mian, Wenguang; Zhang, Feng; Xie, Ming; Sun, Yang; Mei, Qibing

2017-06-05

Treatment of colorectal cancer (CRC) remains a clinical challenge, since current therapies are associated with obvious side effects and high expenses. These limitations highlight an urgent need for developing novel and safe treatment strategies. It is suggested that combinatorial strategies could be more effective and much safer than monotherapy in cancer treatment. In our previous study, an apple oligogalactan (AOG) has been found to show beneficial effect on treating CRC. This study tried to investigate whether AOG could enhance the growth inhibitory effect of 5-FU in human CRC cells (HT-29 and SW-620), a mouse model of colitis associated colorectal cancer and a murine model of xenograft tumor. The IC 50 values of 5-FU were 26.70±0.21μM in HT-29 cells and 26.71±2.06μM in SW-620 cells. Pretreatment with 0.05 or 0.1mM AOG down-regulated IC 50 values of 5-FU to 22.44±1.01 or 18.67±1.16μM in HT-29 and 21.21±1.49 or 17.99±1.42μM in SW-620 cells. AOG enhanced 5-FU-induced cell apoptosis and S phase arrest. The combination not only protected ICR mice against intestinal toxicities and carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate, but also decreased the xenograft tumor size, triggered apoptosis and inhibited proliferation of tumor cells in nude mice. The mechanisms of AOG on enhancing the growth inhibitory effect of 5-FU may be through the influence of TLR-4/NF-κB pathway. Taken together, the combinatorial therapy using AOG and 5-FU is a promising strategy for the treatment of colorectal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Developments in Colorectal Cancer Screening

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... of this page please turn JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of ... at the National Cancer Institute, shared developments in colorectal cancer screening methods with NIH MedlinePlus magazine. What ...

Dietary patterns and the risk of colorectal cancer and adenomas.

Science.gov (United States)

Randi, Giorgia; Edefonti, Valeria; Ferraroni, Monica; La Vecchia, Carlo; Decarli, Adriano

2010-07-01

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.

Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling.

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Toshinori Hinoue

Full Text Available A CpG island methylator phenotype (CIMP is displayed by a distinct subset of colorectal cancers with a high frequency of DNA hypermethylation in a specific group of CpG islands. Recent studies have shown that an activating mutation of BRAF (BRAF(V600E is tightly associated with CIMP, raising the question of whether BRAF(V600E plays a causal role in the development of CIMP or whether CIMP provides a favorable environment for the acquisition of BRAF(V600E. We employed Illumina GoldenGate DNA methylation technology, which interrogates 1,505 CpG sites in 807 different genes, to further study this association. We first examined whether expression of BRAF(V600E causes DNA hypermethylation by stably expressing BRAF(V600E in the CIMP-negative, BRAF wild-type COLO 320DM colorectal cancer cell line. We determined 100 CIMP-associated CpG sites and examined changes in DNA methylation in eight stably transfected clones over multiple passages. We found that BRAF(V600E is not sufficient to induce CIMP in our system. Secondly, considering the alternative possibility, we identified genes whose DNA hypermethylation was closely linked to BRAF(V600E and CIMP in 235 primary colorectal tumors. Interestingly, genes that showed the most significant link include those that mediate various signaling pathways implicated in colorectal tumorigenesis, such as BMP3 and BMP6 (BMP signaling, EPHA3, KIT, and FLT1 (receptor tyrosine kinases and SMO (Hedgehog signaling. Furthermore, we identified CIMP-dependent DNA hypermethylation of IGFBP7, which has been shown to mediate BRAF(V600E-induced cellular senescence and apoptosis. Promoter DNA hypermethylation of IGFBP7 was associated with silencing of the gene. CIMP-specific inactivation of BRAF(V600E-induced senescence and apoptosis pathways by IGFBP7 DNA hypermethylation might create a favorable context for the acquisition of BRAF(V600E in CIMP+ colorectal cancer. Our data will be useful for future investigations toward

Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling.

Science.gov (United States)

Hinoue, Toshinori; Weisenberger, Daniel J; Pan, Fei; Campan, Mihaela; Kim, Myungjin; Young, Joanne; Whitehall, Vicki L; Leggett, Barbara A; Laird, Peter W

2009-12-21

A CpG island methylator phenotype (CIMP) is displayed by a distinct subset of colorectal cancers with a high frequency of DNA hypermethylation in a specific group of CpG islands. Recent studies have shown that an activating mutation of BRAF (BRAF(V600E)) is tightly associated with CIMP, raising the question of whether BRAF(V600E) plays a causal role in the development of CIMP or whether CIMP provides a favorable environment for the acquisition of BRAF(V600E). We employed Illumina GoldenGate DNA methylation technology, which interrogates 1,505 CpG sites in 807 different genes, to further study this association. We first examined whether expression of BRAF(V600E) causes DNA hypermethylation by stably expressing BRAF(V600E) in the CIMP-negative, BRAF wild-type COLO 320DM colorectal cancer cell line. We determined 100 CIMP-associated CpG sites and examined changes in DNA methylation in eight stably transfected clones over multiple passages. We found that BRAF(V600E) is not sufficient to induce CIMP in our system. Secondly, considering the alternative possibility, we identified genes whose DNA hypermethylation was closely linked to BRAF(V600E) and CIMP in 235 primary colorectal tumors. Interestingly, genes that showed the most significant link include those that mediate various signaling pathways implicated in colorectal tumorigenesis, such as BMP3 and BMP6 (BMP signaling), EPHA3, KIT, and FLT1 (receptor tyrosine kinases) and SMO (Hedgehog signaling). Furthermore, we identified CIMP-dependent DNA hypermethylation of IGFBP7, which has been shown to mediate BRAF(V600E)-induced cellular senescence and apoptosis. Promoter DNA hypermethylation of IGFBP7 was associated with silencing of the gene. CIMP-specific inactivation of BRAF(V600E)-induced senescence and apoptosis pathways by IGFBP7 DNA hypermethylation might create a favorable context for the acquisition of BRAF(V600E) in CIMP+ colorectal cancer. Our data will be useful for future investigations toward understanding

Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk

DEFF Research Database (Denmark)

Thrift, Aaron P.; Gong, Jian; Peters, Ulrike

2015-01-01

Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate...... the causal association between BMI and colorectal cancer. Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated......, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer....

Vegetarian dietary patterns and the risk of colorectal cancers.

Science.gov (United States)

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

2015-05-01

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

Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review

Directory of Open Access Journals (Sweden)

Chan Siew F

2011-05-01

Full Text Available Abstract Background Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps. Methods We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps. Results Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7 and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9. Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care nor study type was associated with accuracy. Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies. Conclusions Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into

Significance of Streptococcus gallolyticus subsp. gallolyticus Association With Colorectal Cancer

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Ewa Pasquereau-Kotula

2018-04-01

Full Text Available Streptococcus gallolyticus subsp. gallolyticus Sgg (formerly known as S. bovis type I is the main causative agent of septicemia and infective endocarditis (IE in elderly and immunocompromised persons. It belongs to the few opportunistic bacteria, which have been strongly associated to colorectal cancer (CRC. A literature survey covering a period of 40 years (1970–2010 revealed that 65% of patients diagnosed with an invasive Sgg infection had a concomitant colorectal neoplasia. Sgg is associated mainly with early adenomas and may thus constitute an early marker for CRC screening. Sgg has been described as a normal inhabitant of the rumen of herbivores and in the digestive tract of birds. It is more rarely detected in human intestinal tract (2.5–15%. Recent molecular analyses indicate possible zoonotic transmission of Sgg. Thanks to the development of a genetic toolbox and to comparative genomics, a number of factors that are important for Sgg pathogenicity have been identified. This review will highlight the role of Sgg pili in host colonization and how their phase-variable expression contributes to mitigate the host immune responses and finally their use as serological diagnostic tool. We will then present experimental data addressing the core question whether Sgg is a cause or consequence of CRC. We will discuss a few recent studies examining the etiological versus non-etiological participation of Sgg in colorectal cancer with the underlying mechanisms.

The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis.

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Ida Casorelli

Full Text Available BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/- mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS. The Mutyh(-/- phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/- mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/- mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+ regulatory T cells were observed only in Mutyh(-/- mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

Directory of Open Access Journals (Sweden)

Valerie A. Allen

2016-01-01

Full Text Available Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI. Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

Lysyl oxidase in colorectal cancer

DEFF Research Database (Denmark)

Cox, Thomas R; Erler, Janine T

2013-01-01

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....

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

DEFF Research Database (Denmark)

Hoeft, B.; Linseisen, J.; Beckmann, L.

2010-01-01

as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred......Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

Screening for colorectal cancer.

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He, Jin; Efron, Jonathan E

2011-01-01

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.

Prophylaxis against colorectal cancer

DEFF Research Database (Denmark)

Bülow, Steffen; Kronborg, O

1996-01-01

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....

Colorectal Cancer: A Personal Journey

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... of this page please turn JavaScript on. Feature: Colorectal Cancer Colorectal Cancer: A Personal Journey Past Issues / Summer 2016 Table ... Carmen Marc Valvo is an outspoken voice for colorectal cancer screening. Photo Courtesy of: Phil Fisch Photography Designer ...

Coffee consumption and risk of colorectal cancer.

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Bidel, S; Hu, G; Jousilahti, P; Antikainen, R; Pukkala, E; Hakulinen, T; Tuomilehto, J

2010-09-01

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.

Serum biomarkers of habitual coffee consumption may provide insight into the mechanism underlying the association between coffee consumption and colorectal cancer12345

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Guertin, Kristin A; Loftfield, Erikka; Boca, Simina M; Sampson, Joshua N; Moore, Steven C; Xiao, Qian; Huang, Wen-Yi; Xiong, Xiaoqin; Freedman, Neal D; Cross, Amanda J; Sinha, Rashmi

2015-01-01

Background: Coffee intake may be inversely associated with colorectal cancer; however, previous studies have been inconsistent. Serum coffee metabolites are integrated exposure measures that may clarify associations with cancer and elucidate underlying mechanisms. Objectives: Our aims were 2-fold as follows: 1) to identify serum metabolites associated with coffee intake and 2) to examine these metabolites in relation to colorectal cancer. Design: In a nested case-control study of 251 colorectal cancer cases and 247 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we conducted untargeted metabolomics analyses of baseline serum by using ultrahigh-performance liquid-phase chromatography–tandem mass spectrometry and gas chromatography–mass spectrometry. Usual coffee intake was self-reported in a food-frequency questionnaire. We used partial Pearson correlations and linear regression to identify serum metabolites associated with coffee intake and conditional logistic regression to evaluate associations between coffee metabolites and colorectal cancer. Results: After Bonferroni correction for multiple comparisons (P = 0.05 ÷ 657 metabolites), 29 serum metabolites were positively correlated with coffee intake (partial correlation coefficients: 0.18–0.61; P coffee intake (partial correlation coefficients >0.40) included trigonelline (N′-methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8 metabolites were directly related to caffeine metabolism, and 3 of these metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95% CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear trend = 0.027), were inversely associated with colorectal cancer. Conclusions: Serum metabolites can

Dietary Patterns and the Risk of Colorectal Cancer.

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Fung, Teresa T; Brown, Lisa S

2013-03-01

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.

Perceptions of Malaysian colorectal cancer patients regarding dietary intake: a qualitative exploration.

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Yusof, Afzaninawati Suria; Isa, Zaleha Md; Shah, Shamsul Azhar

2013-01-01

Changes in dietary practices are known to be associated with changes in the health and disease pattern of a population. This study aimed to qualitatively explore the perception of colorectal cancer patients regarding causes of colorectal cancer and the influence of diet. Twelve respondents from three major ethnicities in Malaysia were selected from the quantitative study on dietary pattern and colorectal cancer carried out earlier in this study. In-depth interviews (IDI), conducted from April until June 2012, were mainly in the Malay language with additional use of English and continued until the saturation point was reached. All interviews were autorecorded so that verbatim transcriptions could be created. Causes of colorectal cancer were categorized into internal and external factors. The majority of respondents agreed that there is an association between Western foods and colorectal cancer. Malaysian traditional diet was not related to colorectal cancer as less preservative agents were used. Malaysian diet preparation consisting of taste of cooking (spicy, salty and sour foods) plus type of cooking (fry, grilled and smoked) were considered causes of colorectal cancer. All respondents changed their dietary pattern to healthy food after being diagnosed with colorectal cancer. Advice from doctors regarding suitable food for colorectal cancer was useful in this regard. Eating outside, use of food flavoring ingredients and preservative agents were considered to be the main factors causing colorectal cancer. All respondents admitted that they changed to a healthy diet after being diagnosed with colorectal cancer.

Prophylaxis against colorectal cancer

DEFF Research Database (Denmark)

Bülow, Steffen; Kronborg, O

1996-01-01

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....

Association of Dietary Patterns With Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue.

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Mehta, Raaj S; Nishihara, Reiko; Cao, Yin; Song, Mingyang; Mima, Kosuke; Qian, Zhi Rong; Nowak, Jonathan A; Kosumi, Keisuke; Hamada, Tsuyoshi; Masugi, Yohei; Bullman, Susan; Drew, David A; Kostic, Aleksandar D; Fung, Teresa T; Garrett, Wendy S; Huttenhower, Curtis; Wu, Kana; Meyerhardt, Jeffrey A; Zhang, Xuehong; Willett, Walter C; Giovannucci, Edward L; Fuchs, Charles S; Chan, Andrew T; Ogino, Shuji

2017-07-01

Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' immune response to tumor. Evidence also suggests that diet influences intestinal F nucleatum. However, the role of F nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown. To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F nucleatum in tumor tissue. A prospective cohort study was conducted using data from the Nurses' Health Study (June 1, 1980, to June 1, 2012) and the Health Professionals Follow-up Study (June 1, 1986, to June 1, 2012) on a total of 121 700 US female nurses and 51 529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively (both predominantly white individuals), at enrollment. Data analysis was performed from March 15, 2015, to August 10, 2016. Prudent and Western diets. Incidence of colorectal carcinoma subclassified by F nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction. Of the 173 229 individuals considered for the study, 137 217 were included in the analysis, 47 449 were male (34.6%), and mean (SD) baseline age for men was 54.0 (9.8) years and for women, 46.3 (7.2) years. A total of 1019 incident colon and rectal cancer cases with available F nucleatum data were documented over 26 to 32 years of follow-up, encompassing 3 643 562 person-years. The association of prudent diet with colorectal cancer significantly differed by tissue F nucleatum status (P = .01 for heterogeneity); prudent diet score was associated with a lower risk of F nucleatum-positive cancers (P = .003 for trend; multivariable hazard ratio of 0.43; 95% CI, 0.25-0.72, for the highest vs the lowest prudent score quartile) but not with F nucleatum

Meat consumption and colorectal cancer risk in Japan: The Takayama study.

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Wada, Keiko; Oba, Shino; Tsuji, Michiko; Tamura, Takashi; Konishi, Kie; Goto, Yuko; Mizuta, Fumi; Koda, Sachi; Hori, Akihiro; Tanabashi, Shinobu; Matsushita, Shogen; Tokimitsu, Naoki; Nagata, Chisato

2017-05-01

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population-based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population-based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

[Changes of expression of miR-155 in colitis-associated colonic carcinogenesis].

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Li, Weiwei; Han, Wenxiao; Zhao, Xinhua; Wang, Hongying

2014-04-01

To investigate the changes of miR-155 and its target genes in colitis-associated carcinogenesis. Colitis-associated colon cancer was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice of three different stages during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment and a DSS only group representing chronic inflammation without cancer were set up as well. Colon tissue was collected and expression of miR-155 in the colon tissues was measured by real-time fluorescent quantitative PCR. TargetScan and PicTar were used to predict potential target genes of miR-155, which were then preliminarily screened with our gene expression microarray database of AOM-DSS mouse model. Regular PCR was used to confirm the changes of the expression of these potential target genes in AOM-DSS mouse model. Colitis-associated colon cancer was effectively induced by azoxymethane and dextran sulfate sodium in C57BL/6 mice. Histological examination revealed that the evolution process was sequentially from normal, mild dysplasia, moderate dysplasia, and severe dysplasia to adenocarcinoma in the AOM-DSS mouse model. The level of miR-155 was gradually elevated with the formation of colitis-associated colon cancer. There was no significant difference between the levels of miR-155 expression in the DSS group (0.005 6 ± 0.003 7) and control group (0.012 0 ± 0.005 1) (P > 0.05), but the level of miR-155 in the AD3 group (0.054 4 ± 0.027 0) was significantly higher than that of the DSS group (0.005 6 ± 0.003 7)(P Bcorl1, Cacna1c, Rspo2 and Foxo3 were potential target genes of miR-155 in the AOM-DSS mouse model. Changes of Kcna1 and Cacna1c in the AOM-DSS mouse model were validated to be consistent with the changes obtained with the gene expression microarray. The up-regulation of miR-155 is related to colitis-associated carcinogenesis, but is irrelevant to chronic inflammation in the

[Chinese Protocol of Diagnosis and Treatment of Colorectal Cancer].

Science.gov (United States)

2018-04-01

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.

Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists.

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Phillips, R L; Snowdon, D A

1985-02-01

Associations between fatal colon or colorectal cancer and frequency of use of meat, cheese, milk, eggs, green salad, and coffee, as well as percent desirable weight, are described with the use of 21 years of follow-up for 25,493 white California Seventh-Day Adventists. Associations are presented in terms of relative risk (RR) of colorectal cancer for heavy or light exposure versus rare exposure. There were no clear relationships evident between colon or rectal cancer and meat, cheese, milk, or green salad use. Egg use was positively associated with risk of fatal colon cancer in both males (RR = 1.6) and females (RR = 1.7). Coffee use was positively associated with both colon and rectal cancer mortality in males and females, particularly for colon cancer during the last 11 years of follow-up (male RR = 3.5; female RR = 1.9). Overweight (percent of desirable weight greater than or equal to 125) was associated with an increased risk of fatal rectal cancer in both sexes combined (RR = 2.8) and colon cancer in males only (RR = 3.3). Furthermore, eggs, coffee, and overweight appear to be independently associated with risk of both colon and colorectal cancer. These three factors may explain a substantial portion of the colorectal cancer mortality differential between Adventists and U.S. whites (62% for males; 30% for females).

Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer123

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Cross, Amanda J; Subar, Amy F; Krebs-Smith, Susan M; Park, Yikyung; Powell-Wiley, Tiffany; Hollenbeck, Albert; Reedy, Jill

2013-01-01

Background: Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. Objective: We compared 4 established DASH indexes and examined associations with colorectal cancer. Design: Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. Results: From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). Conclusion: The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results. PMID:23864539

Association of adherence to lifestyle recommendations and risk of colorectal cancer

DEFF Research Database (Denmark)

Kirkegaard, Helene; Johnsen, Nina Føns; Christensen, Jane

2010-01-01

on physical activity, waist circumference, smoking, alcohol intake, and diet (dietary fibre, energy percentage from fat, red and processed meat, and fruits and vegetables)) modelled through Cox regression. RESULTS: During a median follow-up of 9.9 years, 678 men and women had colorectal cancer diagnosed...... have been prevented. Results were similar for colon and rectal cancer, but only statistically significant for colon cancer. CONCLUSIONS: Adherence to the recommendations for physical activity, waist circumference, smoking, alcohol intake, and diet may reduce colorectal cancer risk considerably...

Role of physical activity and diet after colorectal cancer diagnosis.

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Van Blarigan, Erin L; Meyerhardt, Jeffrey A

2015-06-01

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.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

DEFF Research Database (Denmark)

Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

2017-01-01

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...

Physical activity and the risk of colorectal cancer in Lynch syndrome.

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Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S; Glombicki, Stephen E; Mallenahalli, Sheila; Thirumurthi, Selvi; Peterson, Susan K; You, Y Nancy; Buchanan, Daniel D; Figueiredo, Jane C; Campbell, Peter T; Gallinger, Steven; Newcomb, Polly A; Potter, John D; Lindor, Noralane M; Le Marchand, Loic; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Basen-Engquist, Karen M; Lynch, Patrick M; Pande, Mala

2018-06-14

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. Lynch syndrome, however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved. © 2018 UICC.

Microbiota, Inflammation and Colorectal Cancer

Directory of Open Access Journals (Sweden)

Cécily Lucas

2017-06-01

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.

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population.

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Rivu, Sanzana Fareen; Apu, Mohd Nazmul Hasan; Shabnaz, Samia; Nahid, Noor Ahmed; Islam, Md Reazul; Al-Mamun, Mir Md Abdullah; Nahar, Zabun; Rabbi, Sikder Nahidul Islam; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Hasnat, Abul

2017-08-01

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160Ccolorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77-3.77, pcolorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (pcolorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42-2.87, pcolorectal cancer development in Bangladeshi population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vegetarian Dietary Patterns and the Risk of Colorectal Cancers

Science.gov (United States)

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.

2015-01-01

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

Quality of life and its determinants among colorectal cancer survivors

OpenAIRE

Hossein Ali Nikbakht; Nayyereh Amini Sani; Mohamad Asghari Jafarabadi; Seyed Reza Hosseini

2015-01-01

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...

Co-Care: A Registry for Individuals at Increased Risk for Colorectal Cancer.

Science.gov (United States)

Sperling, Dylan; Jandorf, Lina; Sriphanlop, Pathu; Martinez, Clarissa; Brown, Karen L; Soper, Emily R; Hiraki, Susan; Itzkowitz, Steven H

2017-01-01

INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer death for both men and women in the United States. Several factors can increase one’s risk of CRC, including a personal or family history of CRC, a diagnosis or family history of a hereditary colon cancer syndrome, or a diagnosis of chronic inflammatory bowel disease. The purpose of this project was to create a colorectal cancer registry (Co-Care) for individuals with a personal or family history of CRC, and those with disorders of the colon or rectum that are associated with an increased risk for developing CRC. Methods: To be eligible for the registry, patients either had a personal or family history of CRC, a diagnosis or family history of Lynch syndrome, familial adenomatous polyposis, or a diagnosis of Crohn’s colitis or ulcerative colitis with dysplasia. Participants were recruited after seeing their gastroenterologist or genetic counselor, or after undergoing a full or partial colectomy at Mount Sinai Hospital in New York City. Eligible patients who agreed to participate were interviewed by a member of the research staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A total of 224 patients were enrolled in the registry. Participants are mostly white, born in the United States, and married, with a bachelor’s or graduate degree, reporting an annual household income of $100,000 or more. The largest portion have a family history of CRC (27.2%), and almost half of participants are of Jewish descent (46.2%) and have undergone full or partial colectomy (48.2%). More than half of participants have neither received genetic counseling (54.5%) nor undergone genetic testing (59.7%). Only 3.6% report that they currently smoke cigarettes, and 41.1% consume alcohol at least once per week. Lastly, 18.3%, 10.3%, and 27.7% of participants report that they currently take aspirin, folic acid/folate pills or tablets, or calcium pills/tablets, respectively. CONCLUSIONS: This

Obesity and colorectal cancer risk; Obesidad y riesgo de cancer colorrectal

Energy Technology Data Exchange (ETDEWEB)

Hano Garcia, Olga Marina; Wood Rodriguez, Lisette; Villa Jimenez, Oscar Manuel, E-mail: olga.hano@infomed.sld.c [Instituto Nacional de Gastroenterologia, La Habana (Cuba)

2011-07-01

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

Coffee Consumption and the Incidence of Colorectal Cancer in Women

International Nuclear Information System (INIS)

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.

2016-01-01

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.

Dietary patterns and colorectal cancer risk in Japan: the Ohsaki Cohort Study.

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Kumagai, Yumi; Chou, Wan-Ting; Tomata, Yasutake; Sugawara, Yumi; Kakizaki, Masako; Nishino, Yoshikazu; Tsuji, Ichiro

2014-06-01

To evaluate dietary patterns in relation to colorectal cancer risk in Japanese. We prospectively assessed the association between dietary patterns among the Japanese and the risk of colorectal cancer. Dietary information was collected from 44,097 Japanese men and women aged 40-79 years without a history of cancer at the baseline in 1994. During 11 years of follow-up, we documented 854 cases of colorectal cancer, which included 554 cases of colon cancer and 323 cases of rectal cancer. Factor analysis (principal component analysis) based on a validated food frequency questionnaire identified three dietary patterns: (1) a Japanese dietary pattern, (2) an "animal food" dietary pattern, and (3) a high-dairy, high-fruit-and-vegetable, low-alcohol (DFA) dietary pattern. After adjustment for potential confounders, the DFA pattern was inversely associated with the risk of colorectal cancer (hazard ratio of the highest quartile vs the lowest, 0.76; 95 % confidence interval 0.60-0.97; p for trend = 0.02). When colon and rectal cancers were separated, the inverse association between the DFA pattern and cancer risk was observed for rectal cancer (p for trend = 0.003), but not for colon cancer (p for trend = 0.43). No apparent association was observed for either the Japanese dietary pattern or the "animal food" dietary pattern. The DFA dietary pattern was found to be inversely associated with the risk of colorectal cancer. This association was observed for rectal cancer, but not for colon cancer.

Patient and provider characteristics associated with colorectal, breast, and cervical cancer screening among Asian Americans.

Science.gov (United States)

Thompson, Caroline A; Gomez, Scarlett Lin; Chan, Albert; Chan, John K; McClellan, Sean R; Chung, Sukyung; Olson, Cliff; Nimbal, Vani; Palaniappan, Latha P

2014-11-01

Routinely recommended screening for breast, cervical, and colorectal cancers can significantly reduce mortality from these types of cancer, yet screening is underutilized among Asians. Surveys rely on self-report and often are underpowered for analysis by Asian ethnicities. Electronic health records (EHR) include validated (as opposed to recall-based) rates of cancer screening. In this article, we seek to better understand cancer screening patterns in a population of insured Asian Americans. We calculated rates of compliance with cervical, breast, and colorectal cancer screening among Asians from an EHR population and compared them with non-Hispanic whites. We performed multivariable modeling to evaluate potential predictors (at the provider- and patient-level) of screening completion among Asian patients. Aggregation of Asian subgroups masked heterogeneity in screening rates. Asian Indians and native Hawaiians and Pacific Islanders had the lowest rates of screening in our sample, well below that of non-Hispanic whites. In multivariable analyses, screening completion was negatively associated with patient-physician language discordance for mammography [OR, 0.81; 95% confidence interval (CI), 0.71-0.92] and colorectal cancer screening (OR, 0.79; CI, 0.72-0.87) and positively associated with patient-provider gender concordance for mammography (OR, 1.16; CI, 1.00-1.34) and cervical cancer screening (OR, 1.66; CI, 1.51-1.82). In addition, patient enrollment in online health services increased mammography (OR, 1.32; CI, 1.20-1.46) and cervical cancer screening (OR, 1.31; CI, 1.24-1.37). Language- and gender-concordant primary care providers and culturally tailored online health resources may help improve preventive cancer screening in Asian patient populations. This study demonstrates how the use of EHR data can inform investigations of primary prevention practices within the healthcare delivery setting. ©2014 American Association for Cancer Research.

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk.

Science.gov (United States)

Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

2018-01-19

Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; p trend colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer.

Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With Colorectal Cancer.

Science.gov (United States)

Soliman, Basem G; Karagkounis, Georgios; Church, James M; Plesec, Thomas; Kalady, Matthew F

2018-05-01

The incidence of colorectal cancer in the young (under age 40) is increasing, and this population has worse oncologic outcomes. Mucinous histology is a potential prognostic factor in colorectal cancer, but has not been evaluated specifically in young patients. The objective of the study was to determine factors associated with poor outcome in young patients with colorectal cancer (≤40 years) and to determine relationships between mucinous histology and oncologic outcomes in this population. This is a retrospective study. Patients from a single-institution tertiary care center were studied. A total of 224 patients with colorectal cancer under 40 years of age diagnosed between 1990 and 2010 were included (mean age, 34.7 years; 51.3% female). 34 patients (15.2%) had mucinous histology. There were no interventions. Oncologic outcomes were analyzed according to the presence of mucinous histology. The mucinous and nonmucin colorectal cancer study populations were statistically similar in age, sex, tumor location, pathological stage, differentiation, and adjuvant chemotherapy use. Five-year disease-free survival was 29.1% versus 71.3% (p colorectal cancers recurred earlier at a median time of 36.4 months versus 94.2 months for nonmucin colorectal cancers (p colorectal cancer. This is associated with early and high recurrence rates, despite use of standard neoadjuvant and adjuvant regimens. Physicians need to be aware of this association and potentially explore novel treatment options. See Video Abstract at http://links.lww.com/DCR/A575.

Colorectal Cancer Risk Assessment Tool

Science.gov (United States)

... 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 ...

Linking Gut Microbiota to Colorectal Cancer

DEFF Research Database (Denmark)

Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian

2017-01-01

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....

Financial hardship associated with colorectal cancer survivorship: the role of asset depletion and debt accumulation.

Science.gov (United States)

Hanly, Paul; Maguire, Rebecca; Ceilleachair, Alan O; Sharp, Linda

2018-05-31

To estimate the prevalence of financial objective stress and subjective strain among colorectal cancer survivors and assess associated financial coping factors in Ireland which has a mixed public-private healthcare system. Colorectal cancer survivors were identified from the National Cancer Registry and a sample of 496 respondents were included in the analysis. A postal survey collected information on survivor demographics, socio-economic background, medical characteristics, cancer-related financial hardship, debt accumulation and asset depletion. Cancer-related financial objective stress and subjective strain were employed as dependent variables in logistic regression analysis. Approximately two in five survivors experienced objective stress (40.9%) or subjective strain (39.4%). Depletion of savings (49.1%) was the most prevalent form of financial coping strategy. Factors significantly associated with increased objective stress were having a stoma (OR=2.1, 95% CI 1.1-3.9), using savings (OR=9.4, 95% CI 4.9-18.0), formally borrowing money (OR=3.1, 95% CI 1.0-9.6) and loans from family members/friends (OR=3.8, 95% CI 1.9-7.8). Not working (excluding retirees) (OR=0.44, 95% CI 0.20-0.96) was associated with decreased objective stress. Significant predictors of subjective strain included having dependents, a stoma, using savings (OR=5.3 95% CI 2.9-9.5) and loans from family members/friends (OR=2.0, 95% CI 1.1-3.9), but excluded borrowing money. Cancer-related financial objective stress and subjective strain are common in colorectal cancer survivors, even where all citizens are entitled to publicly-funded care, but the financial coping strategies significantly associated with these two measures differed. These findings will help inform targeted measures across disparate health care systems, and survivor groups, to alleviate financial hardship. This article is protected by copyright. All rights reserved.

Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression

International Nuclear Information System (INIS)

Jensen, Søren A; Vainer, Ben; Kruhøffer, Mogens; Sørensen, Jens B

2009-01-01

Microsatellite instability (MSI) refers to mutations in short motifs of tandemly repeated nucleotides resulting from replication errors and deficient mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and chemosensitivity, however the molecular basis remains unclarified. The association of MSI and MMR status with outcome and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were evaluated. MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy. MSI was found in 43 (13.8%) tumors. Absence of repair protein expression was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%), hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI (instable) compared to MSS (stable) tumors were significantly associated with lower risk of recurrence (hazard ratio (HR) = 0.3; 95% CI: 0.2–0.7; P = 0.0007) and death (HR = 0.4; 95% CI: 0.2–0.9; P = 0.02) independently of the TS and DPD expressions. A direct relationship between MSI and TS intensity (P = 0.001) was found, while there was no significant association with DPD intensity (P = 0.1). The favourable outcome of MSI colorectal carcinomas is ascribed mainly to the tumor biology and to a lesser extent to antitumor response to 5-fluorouracil therapy. There is no evidence that differential TS or DPD expression may account for these outcome characteristics

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

Science.gov (United States)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191

Iranian dietary patterns and risk of colorectal cancer.

Science.gov (United States)

Azizi, Hosein; Asadollahi, Khairollah; Davtalab Esmaeili, Elham; Mirzapoor, Mohammad

2015-01-01

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.

Colorectal cancer with venous tumor thrombosis

OpenAIRE

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

2018-01-01

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 ...

Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study.

Science.gov (United States)

Lu, Min-Shan; Fang, Yu-Jing; Pan, Zhi-Zhong; Zhong, Xiao; Zheng, Mei-Chun; Chen, Yu-Ming; Zhang, Cai-Xia

2015-01-01

Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population. A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval) and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs). Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake. These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.

Ziv-aflibercept in metastatic colorectal cancer

Directory of Open Access Journals (Sweden)

Patel A

2013-12-01

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

Perceived religiousness is protective for colorectal cancer: data from the Melbourne Colorectal Cancer Study.

OpenAIRE

Kune, G A; Kune, S; Watson, L F

1993-01-01

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, ...

Update on Sporadic Colorectal Cancer Genetics.

Science.gov (United States)

Hardiman, Karin M

2018-05-01

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.

Role of β1-Integrin in Colorectal Cancer: Case-Control Study

Science.gov (United States)

Oh, Bo-Young; Kim, Kwang Ho; Chung, Soon Sup; Hong, Kyoung Sook

2014-01-01

Purpose In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-Integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer. Methods We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups. In the experimental group, preoperative results were compared with postoperative results for each marker. In addition, we analyzed the correlation between the expressions of β1-integrin and CEA. Results CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P = 0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P = 0.032). β1-Integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P < 0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P = 0.033) and was significantly decreased after surgery (P < 0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P = 0.001). Conclusion In conclusion, β1-integrin is a potential factor for forming a prognosis following surgical resection in colorectal cancer patients. β1-Integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients. PMID:24851215

Screening for colorectal cancer in defunctioned colons.

Science.gov (United States)

Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

2018-01-01

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.

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

Science.gov (United States)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

2016-09-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Endoscopic, epidemiologic and clinic characterization of the colorectal cancer in geriatric patients;Caracterizacion clinica, epidemiologica y endoscopica del cancer colorrectal en pacientes geriatricos

Energy Technology Data Exchange (ETDEWEB)

Umpierrez Garcia, Ibis [Hospital Militar Docente ' Dr Mario Munnoz Monroy' , Matanzas (Cuba); Norma, Herrera Hernandez [Hospital Universitario Clinico-Quirurgico ' Cmdte Faustino Perez Hernandez' Matanzas (Cuba); Hernandez Ortega, Ania [Hospital Territorial Docente ' Mario Munnoz Monroy' , Municipio de Colon, Matanzas (Cuba)

2009-07-01

The colorectal cancer is a serious health problem because of its high incidence. In Cuba, this disease is the fourth neoplasm in order of frequency with a rate of 17.1 per 100 000 inhabitants. With the objective of determining the precocious diagnosis of this complaint we carried out a prospective, longitudinal and descriptive study among geriatric patients with colorectal disease assisting to consultation at the policlinic 'Carlos Verdugo' of Matanzas in the period from January 2006 to December 2007. The studied parameters were age, genre, risk facts, presentation forms, localization, and endoscopic diagnosis of the disease. The results showed predominance of female sex (52,1 %), in ages from 60 to 69 years old (59.3 %), predominating risk facts like familiar antecedents (13,5 %), idiopathic ulcerative colitis (8.1 %), and an inadequate diet (35.1 %). The most used diagnostic method was colonoscopy (18 patients), with predominance of the rectosigmoidal cancer (15 cases), being the polypoid one the most common endoscopic kind (13 %). We concluded that generally there is not a precocious diagnosis of the colorectal cancer among geriatric patients, leading to a decrease of the healing possibilities and surviving of these patients

Involvement of hyaluronidases in colorectal cancer

International Nuclear Information System (INIS)

Bouga, Helen; Tsouros, Isidoros; Bounias, Dimitrios; Kyriakopoulou, Dora; Stavropoulos, Michael S; Papageorgakopoulou, Nikoletta; Theocharis, Dimitrios A; Vynios, Demitrios H

2010-01-01

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

CpG island methylator phenotype-low (CIMP-low) in colorectal cancer: possible associations with male sex and KRAS mutations.

Science.gov (United States)

Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Loda, Massimo; Fuchs, Charles S

2006-11-01

The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation seems to be a distinct epigenotype of colorectal cancer. However, no study has comprehensively examined features of colorectal cancer with less extensive promoter methylation (designated as "CIMP-low"). Using real-time polymerase chain reaction (MethyLight), we quantified DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1] in 840 relatively unbiased, population-based colorectal cancer samples, obtained from two large prospective cohort studies. CIMP-low (defined as 1/5 to 3/5 methylated promoters) colorectal cancers were significantly more common among men (38 versus 30% in women, P = 0.01) and among KRAS-mutated tumors (44 versus 30% in KRAS/BRAF wild-type tumors, P = 0.0003; 19% in BRAF-mutated tumors, P CIMP-low tumors (47%) than in CIMP-high tumors (with > or =4/5 methylated promoters, 12%, P CIMP-0 tumors (with 0/5 methylated promoters, 37%, P = 0.007). The associations of CIMP-low tumors with male sex and KRAS mutations still existed after tumors were stratified by microsatellite instability status. In conclusion, CIMP-low colorectal cancer is associated with male sex and KRAS mutations. The hypothesis that CIMP-low tumors are different from CIMP-high and CIMP-0 tumors needs to be tested further.

Cost-effectiveness of colorectal cancer screening

NARCIS (Netherlands)

I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

2011-01-01

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

High consumption of vegetable and fruit colour groups is inversely associated with the risk of colorectal cancer: a case-control study.

Science.gov (United States)

Luo, Wei-Ping; Fang, Yu-Jing; Lu, Min-Shan; Zhong, Xiao; Chen, Yu-Ming; Zhang, Cai-Xia

2015-04-14

The colour of the edible portion of vegetables and fruit reflects the presence of specific micronutrients and phytochemicals. No existing studies have examined the relationship between the intake of vegetable and fruit colour groups and the risk of colorectal cancer. The present study, therefore, aimed to investigate these associations in a Chinese population. A case-control study was conducted between July 2010 and July 2014 in Guangzhou, China, in which 1057 consecutively recruited cases of colorectal cancer were frequency-matched to 1057 controls by age (5-year interval), sex and residence (rural/urban). A validated FFQ was used to collect dietary information during face-to-face interviews. Vegetables and fruit were classified into four groups according to the colour of their primarily edible parts: green; orange/yellow; red/purple; white. Unconditional logistic regression models were used to estimate the OR and 95 % CI. A higher consumption of orange/yellow, red/purple and white vegetables and fruit was inversely associated with the risk of colorectal cancer, with adjusted OR of 0·16 (95 % CI 0·12, 0·22) for orange/yellow, 0·23 (95 % CI 0·17, 0·31) for red/purple and 0·53 (95 % CI 0·40, 0·70) for white vegetables and fruit when the highest and lowest quartiles were compared. Total vegetable intake and total fruit intake have also been found to be inversely associated with colorectal cancer risk. However, the intake of green vegetable and fruit was not associated with colorectal cancer risk. The results of the present study, therefore, suggest that a greater intake of orange/yellow, red/purple and white vegetables and fruit is inversely associated with the risk of colorectal cancer.

Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

African Journals Online (AJOL)

Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

Dietary calcium intake and the risk of colorectal cancer: a case control study.

Science.gov (United States)

Han, Changwoo; Shin, Aesun; Lee, Jeonghee; Lee, Jeeyoo; Park, Ji Won; Oh, Jae Hwan; Kim, Jeongseon

2015-12-16

High intake of dietary calcium has been thought to be a protective factor against colorectal cancer. To explore the dose-response relationship in the associations between dietary calcium intake and colorectal cancer risk by cancer location, we conducted a case-control study among Korean population, whose dietary calcium intake levels are relatively low. The colorectal cancer cases and controls were recruited from the National Cancer Center in Korea between August 2010 and August 2013. Information on dietary calcium intake was assessed using a semi-quantitative food frequency questionnaire and locations of the colorectal cancers were classified as proximal colon cancer, distal colon cancer, and rectal cancer. Binary and polytomous logistic regression models were used to evaluate the association between dietary calcium intake and risk of colorectal cancer. A total of 922 colorectal cancer cases and 2766 controls were included in the final analysis. Compared with the lowest calcium intake quartile, the highest quartile group showed a significantly reduced risk of colorectal cancer in both men and women. (Odds ratio (OR): 0.16, 95% confidence interval (CI): 0.11-0.24 for men; OR: 0.16, 95% CI: 0.09-0.29 for women). Among the highest calcium intake groups, decrease in cancer risk was observed across all sub-sites of colorectum in both men and women. In conclusion, calcium consumption was inversely related to colorectal cancer risk in Korean population where national average calcium intake level is relatively lower than Western countries. A decreased risk of colorectal cancer by calcium intake was observed in all sub-sites in men and women.

TIMP-1 expression in human colorectal cancer is associated with TGF-B1, LOXL2, INHBA1, TNF-AIP6 and TIMP-2 transcript profiles

DEFF Research Database (Denmark)

Offenberg, Hanne Kjær; Brunner, Nils; Mansilla, Francisco

2008-01-01

colorectal cancer (CRC) and the other TIMPs 2-4, which have also been associated with the progression of colorectal cancer. Genome-wide expression profiling of 172 CRC and normal mucosa samples was used to identify transcript changes for the genes under investigation. We found that TIMP-1 was up...... with the synthesis of extracellullar matrix, genes involved in the TGF-beta signalling pathway, and genes that are likely transcribed by the tumour cells. These insights add to the complex picture emerging about the regulation of TIMPs in colorectal cancer....... that colorectal cancer patients have increased plasma levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1), and that high plasma TIMP-1 levels are associated with short colorectal cancer patient survival. However, although TIMP-1 has been extensively studied in cancer, very little is known about how...

Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers.

Science.gov (United States)

Dashti, S Ghazaleh; Buchanan, Daniel D; Jayasekara, Harindra; Ait Ouakrim, Driss; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid M; Macrae, Finlay A; Giles, Graham G; Parry, Susan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loïc; Thibodeau, Stephen N; Lindor, Noralane M; Newcomb, Polly A; Potter, John D; Baron, John A; Hopper, John L; Jenkins, Mark A; Win, Aung Ko

2017-03-01

Background: People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive. Methods: 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between alcohol consumption and colorectal cancer. Results: Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (SD) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 g/day and >28 g/day was associated with increased colorectal cancer risk (HR, 1.50; 95% CI, 1.09-2.07 and 1.69; 95% CI, 1.07-2.65, respectively; P trend = 0.05), and colon cancer risk (HR, 1.78; 95% CI, 1.27-2.49 and 1.94; 95% CI, 1.19-3.18, respectively; P trend = 0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk. Conclusions: Our data suggest that alcohol consumption, particularly more than 28 g/day of ethanol (∼2 standard drinks of alcohol in the United States), is associated with increased colorectal cancer risk for MMR gene mutation carriers. Impact: Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk. Cancer Epidemiol Biomarkers Prev; 26(3); 366-75. ©2016 AACR . ©2016 American Association for Cancer Research.

[Oligometastasized colorectal cancer-modern treatment strategies].

Science.gov (United States)

Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

2018-06-05

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.

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer.

Science.gov (United States)

Aykut, Berk; Ochs, Markus; Radhakrishnan, Praveen; Brill, Adrian; Höcker, Hermine; Schwarz, Sandra; Weissinger, Daniel; Kehm, Roland; Kulu, Yakup; Ulrich, Alexis; Schneider, Martin

2017-08-22

The Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. We aimed to assess the prognostic significance of EMX2 expression in stage III colorectal adenocarcinoma. Expression levels of EMX2 in human colorectal cancer and adjacent mucosa were assessed by qRT-PCR technology, and results were correlated with clinical and survival data. siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed in order to investigate its effects on the migration of colorectal cancer cells in vitro. Compared to corresponding healthy mucosa, colorectal tumor samples had decreased EMX2 expression levels. Furthermore, EMX2 down-regulation in colorectal cancer tissue was associated with distant metastasis (M1) and impaired overall patient survival. In vitro knockdown of EMX2 resulted in increased tumor cell migration. Conversely, overexpression of EMX2 led to an inhibition of tumor cell migration. EMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. EMX2 might thus represent a promising therapeutic target in colorectal cancer.

Validation of genetic polymorphisms associated to the toxicity of chemotherapy in colorectal cancer patients

Directory of Open Access Journals (Sweden)

L. Cortejoso

2014-07-01

Full Text Available Objective: To validate the associations previously found in three cohorts of patients from the General University Hospital Gregorio Marañón, between the polymorphisms rs1128503, rs2032582 and rs1045642 of the ABCB1 gene and the hand-foot syndrome and diarrhea in colorectal cancer patients treated with chemotherapy regimes containing Capecitabine and 5-Fluorouracil, respectively, and between the polymorphisms rs2297595 of the DPYD gene and nausea/vomiting, rs11615 of ERCC1 and neutropenia, and rs28399433 CYP2A6 and neutropenia, in colorectal cancer patients treated with FOLFOX or XELOX as adjuvant therapy. Method: Colorectal cancer patients treated with chemotherapy regimes, containing Capecitabine (n = 157, 5-Fluorouracil (n = 99 were included in the study, as well as patients treated with XELOX or FOLFOX (n = 83 as adjuvant therapy. The patients included were recruited from the Doce de Octubre University Hospital and from the Gregorio Marañón General University Hospital, and signed the informed consent form. DNA was obtained from blood samples. Genotyping was carried out with SNaPshot. Contingency tables were created for analyzing the associations between the genotypes and the adverse reactions. Results: None of the associations previously identified was replicated in the validation cohort. Conclusions: Pharmacogenetic studies with a limited sample size must be validated with bigger cohorts, if possible by means of multicentre studies, reducing the variables to the maximum and should never be used in clinical practice without validation.

Association of oncogenic bacteria with colorectal cancer in South China.

Science.gov (United States)

Zhou, Youlian; He, Hanchang; Xu, Haoming; Li, Yingfei; Li, Zhiming; Du, Yanlei; He, Jie; Zhou, Yongjian; Wang, Hong; Nie, Yuqiang

2016-12-06

To quantify Fusobacterium spp., Enterococcus faecalis (E.faecalis), Enterotoxigenic Bacteroides fragilis (ETBF), and Enteropathogenic Escherichia coli in colorectal cancer (CRC) patients and their possible association with CRC clinicopathogical features, we collected the resected tumors and adjacent normal tissues (N) from 97 CRC patients. 48 age- and sex-matched healthy controls (HC) were also recruited. Real-time PCR was used for bacterial quantification. The median abundance ofFusobacterium spp.(p colon tissue in the proximity of the tumor.

Iranian Dietary Patterns and Risk of Colorectal Cancer

Directory of Open Access Journals (Sweden)

Hosein Azizi

2015-03-01

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.

Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study.

Directory of Open Access Journals (Sweden)

Min-Shan Lu

Full Text Available Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population.A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs and 95% confidence intervals (CIs. Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend <0.01 comparing the highest with the lowest quartile. No significant associations were observed for betaine or total choline+betaine intakes. For choline-containing compounds, lower colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake.These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.

Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue.

Directory of Open Access Journals (Sweden)

Ying Lu

Full Text Available We previously showed that L-arginine (Arg accumulates in colorectal cancer tissues. The aim of this study was to investigate the mechanism by which Arg accumulates and determine its biological significance. The concentration of Arg and Citrulline (Cit in sera and tumor tissues from colorectal cancer (CRC patients was analyzed by high-performance liquid chromatography (HPLC. The expression of Arg transporters was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemical analysis of tissue microarray. We also transfected the colon cancer cell line HCT-116 with siRNA specific for the Arg transporter CAT-1 and measured the induction of apoptosis by flow cytometry and cell proliferation by MTT assay. Consistent with our previous results, serum Arg and Cit concentrations in colorectal cancer patients were significantly lower than those in normal volunteers, while Arg and Cit concentrations in colorectal cancer tissues were significantly higher than in matched adjacent normal colon tissues. Quantitative RT-PCR showed that the CAT-1 gene was highly overexpressed in 70.5% of colorectal cancer tissue samples relative to adjacent normal colon tissues in all 122 patients with colorectal cancer. Immunohistochemical analysis of tissue microarray confirmed that the expression of CAT-1 was higher in all 25 colorectal cancer tissues tested. CAT-1 siRNA significantly induced apoptosis of HCT-116 cells and subsequently inhibited cell growth by 20-50%. Our findings indicate that accumulation of L-Arg and Cit and cell growth in colorectal cancer tissues is associated with over-expression of the Arg transporter gene CAT-1. Our results may be useful for the development of molecular diagnostic tools and targeted therapy for colorectal cancer.

Screening for colorectal cancer

DEFF Research Database (Denmark)

Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.

2011-01-01

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....

Danish Colorectal Cancer Group Database

DEFF Research Database (Denmark)

Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

2016-01-01

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...

Meat consumption, heterocyclic amines and colorectal cancer risk: the Multiethnic Cohort Study.

Science.gov (United States)

Ollberding, Nicholas J; Wilkens, Lynne R; Henderson, Brian E; Kolonel, Laurence N; Le Marchand, Loïc

2012-10-01

Greater consumption of red and processed meat has been associated with an increased risk of colorectal cancer in several recent meta-analyses. Heterocyclic amines (HCAs) have been hypothesized to underlie this association. In this prospective analysis conducted within the Multiethnic Cohort Study, we examined whether greater consumption of total, red or processed meat was associated with the risk of colorectal cancer among 165,717 participants who completed a detailed food frequency questionnaire at baseline. In addition, we examined whether greater estimated intake of HCAs was associated with the risk of colorectal cancer among 131,763 participants who completed a follow-up questionnaire that included a meat-cooking module. A total of 3,404 and 1,757 invasive colorectal cancers were identified from baseline to the end of follow-up and from the date of administration of the meat-cooking module to the end of follow-up, respectively. Proportional hazard models were used to estimate basic and multivariable-adjusted relative risks (RRs) and 95% confidence intervals for colorectal cancer associated with dietary exposures. In multivariable models, no association with the risk of colorectal cancer was detected for density-adjusted total meat (RR(Q5 vs. Q1) = 0.93 [0.83-1.05]), red meat (RR = 1.02 [0.91-1.16]) or processed meat intake (RR = 1.06 [0.94-1.19]) or for total (RR = 0.90 [0.76-1.05]) or specific HCA intake whether comparing quintiles of dietary exposure or using continuous variables. Although our results do not support a role for meat or for HCAs from meat in the etiology of colorectal cancer, we cannot rule out the possibility of a modest effect. Copyright © 2012 UICC.

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

Science.gov (United States)

Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

2018-01-01

Background Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Results Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; ptrendcolorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). Methods A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Conclusions Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer. PMID:29464080

Colorectal cancer screening

OpenAIRE

McLoughlin, Monica Ramona

2008-01-01

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...

Chinese peoples' perceptions of colorectal cancer screening: a New Zealand perspective.

Science.gov (United States)

Bong, Genevieve; McCool, Judith

2011-03-25

A national cancer screening programme requires a level of perceived acceptability of the procedure among the target population groups to be successful (that is, achieve a high uptake rate). In this study we explored Chinese immigrants' attitudes and perceptions towards colorectal cancer screening. A grounded theory methodology was used explore the determinants of colorectal cancer screening. In depth one-on-one interviews were conducted and subsequently analysed to develop an appreciation of the perspectives on colorectal cancer screening among Chinese people living in New Zealand. Findings indicated a high degree of perceived acceptability for the concept of a national colorectal cancer screening programme. Chinese participants valued health care and preventive health measures were highly prioritised. However, colorectal cancer suffered from the 'poor cousin' syndrome whereby other more highly publicised cancers, such breast cancer, or skin cancer, were perceived to be more relevant and serious, thus marginalising the perceived priority of colorectal cancer screening. Overall, participants paid close attention to their bodies' balance and were proactive in seeking medical advice. Patient practitioner interaction was also found to be influential in the patient's decision to seek screening. The results of the study suggest that the introduction of a colorectal cancer screening programme in New Zealand would benefit from close attention to cultural determinants of screening uptake to provide an equitable service and outcome. Chinese patients who are eligible for participating in the colorectal cancer screening would benefit from access to appropriately detailed and culturally relevant information on the risks, benefit and procedures associated with colorectal cancer screening.

Inflammatory Dietary Pattern, IL-17F Genetic Variant, and the Risk of Colorectal Cancer.

Science.gov (United States)

Cho, Young Ae; Lee, Jeonghee; Oh, Jae Hwan; Chang, Hee Jin; Sohn, Dae Kyung; Shin, Aesun; Kim, Jeongseon

2018-06-05

A proinflammatory diet may increase the risk of colorectal cancer, but its role may differ according to individuals' genetic variants. We aimed to examine whether a specific dietary pattern reflecting inflammation was associated with a risk of colorectal cancer and whether IL-17F genetic variant altered this association. In a study of 695 colorectal cancer cases and 1846 controls, we derived a reduced rank regression dietary pattern using 32 food groups as predictors and the plasma C-reactive protein (CRP) concentration as the response. High CRP levels were associated with a high risk of colorectal cancer (OR (95% CI) = 3.58 (2.65⁻4.82) for the highest quartile vs. lowest quartile). After adjusting for potential confounding factors, high pattern scores were associated with a high risk of colorectal cancer (OR (95% CI) = 9.98 (6.81⁻14.62) for the highest quartile vs. lowest quartile). When stratified by the IL-17F rs763780 genotype, this association was stronger for individuals carrying the C allele ( p for interaction = 0.034), particularly for individuals with rectal cancer ( p for interaction = 0.011). In conclusion, a dietary pattern reflecting inflammation was significantly associated with colorectal cancer risk. Moreover, this association could be modified according to the IL-17F rs763780 genotype and anatomic site.

Autoimmune hepatitis in association with lymphocytic colitis.

LENUS (Irish Health Repository)

Cronin, Edmond M

2012-02-03

Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

Colorectal cancer in Malaysia: Its burden and implications for a multiethnic country.

Science.gov (United States)

Veettil, Sajesh K; Lim, Kean Ghee; Chaiyakunapruk, Nathorn; Ching, Siew Mooi; Abu Hassan, Muhammad Radzi

2017-11-01

This study aims to provide an analytical overview of the changing burden of colorectal cancer and highlight the implementable control measures that can help reduce the future burden of colorectal cancer in Malaysia. We performed a MEDLINE search via OVID with the ​Medical Subject Headings (MeSH) terms "Colorectal Neoplasms"[Mesh] and "Malaysia"[Mesh], and PubMed with the key words "colorectal cancer" and "Malaysia" from 1990 to 2015 for studies reporting any clinical, societal, and economical findings associated with colorectal cancer in Malaysia. Incidence and mortality data were retrieved from population-based cancer registries/databases. In Malaysia, colorectal cancer is the second most common cancer in males and the third most common cancer in females. The economic burden of colorectal cancer is substantial and is likely to increase over time in Malaysia owing to the current trend in colorectal cancer incidence. In Malaysia, most patients with colorectal cancer have been diagnosed at a late stage, with the 5-year relative survival by stage being lower than that in developed Asian countries. Public awareness of the rising incidence of colorectal cancer and the participation rates for colorectal cancer screening are low. The efficiency of different screening approaches must be assessed, and an organized national screening program should be developed in a phased manner. It is essential to maintain a balanced investment in awareness programs targeting general population and primary care providers, focused on increasing the knowledge on symptoms and risk factors of colorectal cancer, awareness on benefits of screening, and promotion of healthy life styles to prevent this important disease. Copyright © 2016. Published by Elsevier Taiwan.

Prospective study of dietary patterns and colorectal cancer among Singapore Chinese.

Science.gov (United States)

Butler, L M; Wang, R; Koh, W-P; Yu, M C

2008-11-04

An influence of Western diet and lifestyle factors observed among Singapore Chinese may contribute to the population's marked rise in colorectal cancer incidence over the past two decades. Thus far, however, there is little evidence for individual nutrients and foods as major contributing factors in this population. We evaluated whether patterns of food intake were associated with colorectal cancer in a population-based cohort of 61,321 Singapore Chinese that was established in 1993-98. Two dietary patterns, meat-dim sum and vegetable-fruit-soy, were previously identified by principal components analysis using baseline dietary data from a validated 165-item food frequency questionnaire. As of 31 December 2005, 961 incident colorectal cancer cases were diagnosed. Proportional hazards regression was used to calculate adjusted hazard ratios. Using nearly 10 years of follow-up data, we observed no association with either the meat-dim sum or vegetable-fruit-soy pattern for colorectal cancer. In conclusion, neither individual nutrients or foods nor dietary patterns appear to explain the rise in colorectal cancer among Singapore Chinese population.

Genome-wide diet-gene interaction analyses for risk of colorectal cancer.

Directory of Open Access Journals (Sweden)

Jane C Figueiredo

2014-04-01

Full Text Available Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3 and processed meat consumption (OR = 1.17; p = 8.7E-09, which was consistently observed across studies (p heterogeneity = 0.78. The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively and null among those with the GG genotype (OR = 1.03. Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.

Poor prognostic role of the pretreatment platelet counts in colorectal cancer: A meta-analysis.

Science.gov (United States)

Rao, Xu-Dong; Zhang, Hua; Xu, Zheng-Shui; Cheng, Hua; Shen, Wei; Wang, Xin-Ping

2018-06-01

Recently, a wide variety of studies have suggested that elevated platelet counts are associated with survival in patients with colorectal cancer. On one hand several studies suggest a negative connection in colorectal cancer patients with pre-operative thrombocytosis, on the other hand other studies contradicts this. However, it remains unknown whether elevated platelet counts are associated with survival in colorectal cancer patients. We therefore conducted this meta-analysis to evaluate the prognostic role of platelet counts in colorectal cancer. PubMed, Embase, and the Cochrane Library databases were searched from their inception to October 15, 2016 to identify relevant studies that have explored the prognostic role of platelet counts in colorectal cancer. Studies that examined the association between platelet counts and prognoses in colorectal cancer and that provided a hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) and/or disease-free survival (DFS) were included. This meta-analysis included 9 retrospective cohort studies involving 3413 patients with colorectal cancer. OS was shorter in patients with elevated platelet counts than in patients with normal counts (HR 2.11, 95% CI: 1.68-2.65). For DFS, an elevated platelet count was also a poor predictor (HR 2.51, 95% CI: 1.84-3.43). In this meta-analysis, we suggest that an elevated platelet count is a negative predictor of survival in both primary colorectal cancer and resectable colorectal liver metastases.

The Synchronous Prevalence of Colorectal Neoplasms in Patients with Stomach Cancer

Science.gov (United States)

Lee, Sang Su; Kim, Cha Young; Ha, Chang Yoon; Min, Hyun Ju; Kim, Hyun Jin; Kim, Tae Hyo

2011-01-01

Purpose The association between stomach cancer and colorectal cancer is controversial. The purpose of this study was to determine the synchronous prevalence of colorectal neoplasms in patients with stomach cancer. Methods A total of 123 patients with stomach cancer (86 male) and 246 consecutive, age- and sex-matched persons without stomach cancer were analyzed from July 2005 to June 2010. All of them underwent colonoscopy within 6 months after undergoing gastroscopy. Results The prevalence of colorectal neoplasms was significantly higher in the stomach cancer group (35.8%) than in the control group (17.9%) (P neoplasms were more prevalent in the patients with stomach cancer (odds ratio [OR], 3.10; 95% confidence interval [CI], 1.71 to 5.63). In particular, the difference in the prevalence of colorectal neoplasms was more prominent in the patients above 50 years old (OR, 3.54; 95% CI, 1.80 to 6.98). Conclusion The results showed that the synchronous prevalence of colorectal neoplasms was higher in patients with stomach cancer than in those without stomach cancer. Therefore, patients with stomach cancer should be regarded as a high-risk group for colorectal neoplasms, and colonoscopy should be recommended for screening. PMID:22102975

Risk of Colorectal Cancer and Associated Mortality in HIV: A Systematic Review and Meta-Analysis.

Science.gov (United States)

OʼNeill, Tyler J; Nguemo, Joseph D; Tynan, Anne-Marie; Burchell, Ann N; Antoniou, Tony

2017-08-01

As people with HIV live longer, the numbers of colorectal cancer cases are expected to increase. We sought to compare the colorectal cancer incidence and cause-specific mortality among people living with and without HIV. Systematic review and meta-analysis. We searched 5 electronic databases up to June 28, 2016, for primary studies reporting standardized incidence ratios (SIRs), standardized mortality ratios (SMRs)/hazard ratios or data sufficient for estimating these summary measures. We performed a random effects pooled analysis to estimate SIR and SMR of colorectal cancer in HIV. Of 8110 articles, we included 27 studies from North America (n = 18), Europe (n = 7), the Pacific region (n = 4), and South America (n = 1). Overall, 1660 cases of colorectal cancer and colon cancer (excluding rectal cancer) occurred among 1,696,070 persons with HIV. In pooled analysis, we found no summary risk of malignancy among those with HIV relative to an uninfected population (SIR 1.00; 95% confidence interval 0.82 to 1.22; I = 89.2%). Colorectal cancer-specific mortality was higher among people with HIV but did not reach statistical significance (SMR 2.09; 95% confidence interval: 1.00 to 4.40; I = 85.0%). Rates of colorectal cancer are similar between people with and without HIV. Existing screening guidelines are likely adequate for people with HIV.

Diagnostic Ultrasound in Colorectal Cancer

DEFF Research Database (Denmark)

Rafaelsen, Søren Rafael

2014-01-01

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

Patient and provider characteristics associated with colorectal, breast, and cervical cancer screening among Asian Americans

Science.gov (United States)

Thompson, Caroline A.; Gomez, Scarlett Lin; Chan, Albert; Chan, John K.; McClellan, Sean R.; Chung, Sukyung; Olson, Cliff; Nimbal, Vani; Palaniappan, Latha P.

2014-01-01

BACKGROUND Routinely recommended screening for breast, cervical, and colorectal cancers can significantly reduce mortality from these types of cancer, yet screening is underutilized among Asians. Surveys rely on self-report and often are underpowered for analysis by Asian ethnicities. Electronic health records include validated (as opposed to recall-based) rates of cancer screening. In this paper we seek to better understand cancer screening patterns in a population of insured Asian Americans. METHODS We calculated rates of compliance with cervical, breast, and colorectal cancer screening among Asians from an EHR population, and compared them to non-Hispanic whites. We performed multivariable modeling to evaluate potential predictors (at the provider- and patient- level) of screening completion among Asian patients. RESULTS Aggregation of Asian subgroups masked heterogeneity in screening rates. Asian Indians and Native Hawaiians and Pacific Islanders had the lowest rates of screening in our sample, well below that of non-Hispanic whites. In multivariable analyses, screening completion was negatively associated with patient-physician language discordance for mammography (OR:0.81 95% CI:0.71–0.92) and colorectal cancer screening (OR:0.79 CI:0.72–0.87) and positively associated with patient-provider gender concordance for mammography (OR:1.16 CI:1.00–1.34) and cervical cancer screening (OR:1.66 CI:1.51–1.82). Additionally, patient enrollment in online health services increased mammography (OR:1.32 CI:1.20–1.46) and cervical cancer screening (OR:1.31 CI:1.24–1.37). CONCLUSIONS Language- and gender- concordant primary care providers, and culturally tailored online health resources may help improve preventive cancer screening in Asian patient populations. IMPACT This study demonstrates how use of EHR data can inform investigations of primary prevention practices within the healthcare delivery setting. PMID:25368396

Toward standardizing and reporting colorectal cancer screening indicators on an international level: The International Colorectal Cancer Screening Network

NARCIS (Netherlands)

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.

2012-01-01

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

Meat and colo-rectal cancer.

Science.gov (United States)

Hill, M J

1999-05-01

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.

Microsatellite Status of Primary Colorectal Cancer Predicts the Incidence of Postoperative Colorectal Neoplasms.

Science.gov (United States)

Takiyama, Aki; Tanaka, Toshiaki; Yamamoto, Yoko; Hata, Keisuke; Ishihara, Soichiro; Nozawa, Hiroaki; Kawai, Kazushige; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Watanabe, Toshiaki

2017-10-01

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.

Lgr5 Methylation in Cancer Stem Cell Differentiation and Prognosis-Prediction in Colorectal Cancer.

Directory of Open Access Journals (Sweden)

Shasha Su

Full Text Available Leucine-rich-repeat-containing G-protein-coupled receptor 5 (lgr5 is a candidate marker for colorectal cancer stem cells (CSC. In the current study, we investigated the methylation status within thelgr5 promoter and evaluated its relationship with CSC differentiation, prognosis for colorectal cancer, and its clinicopathological features.The methylation status within Lgr5 promoter was detected with a methylation-specific PCR in six colorectal cancer cell lines as well as 169 primary colorectal tumor tissues. Differentiation of CSC was examined with immunofluorescence and immunocytochemistry. Down-regulation of lgr5 was achieved with gene-specific siRNA. The associations between lgr5 methylation and the clinicopathological features as well as survival of patients were analyzed with statistical methods.The lgr5 promoter was methylated to different degrees for the six colorectal cell lines examined, with complete methylation observed in HCT116 cells in which the lgr5 expression was partially recovered following DAC treatment. The stem-cell sphere formation from HCT116 cells was accompanied by increasing methylation within the lgr5 promoter and decreasing expression of lgr5. Knocking down lgr5 by siRNA also led to stem-cell spheres formation. Among primary colorectal tumors, 40% (67/169 were positive for lgr5 methylation, while none of the normal colon tissues were positive for lgr5 methylation. Furthermore, lgr5 methylation significantly associated with higher tumor grade, and negative distant metastasis (p < 0.05, as well as better prognosis (p = 0.001 in patients with colorectal cancer.Our data suggests that lgr5 methylation, through the regulation of lgr5 expression and colorectal CSC differentiation, may constitute a novel prognostic marker for colorectal cancer patients.

Colorectal Cancer Awareness for Women via Facebook: A Pilot Study.

Science.gov (United States)

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.

Financial Impact of Colorectal Cancer and Its Consequences: Associations Between Cancer-Related Financial Stress and Strain and Health-Related Quality of Life.

Science.gov (United States)

Sharp, Linda; O'Leary, Eamonn; O'Ceilleachair, Alan; Skally, Mairead; Hanly, Paul

2018-01-01

The financial impact and consequences of cancer on the lives of survivors remain poorly understood. This is especially true for colorectal cancer. We investigated objective cancer-related financial stress, subjective cancer-related financial strain, and their association with health-related quality of life in colorectal cancer survivors. This was a cross-sectional postal survey. The study was conducted in Ireland, which has a mixed public-private healthcare system. Colorectal cancer survivors, diagnosed 6 to 37 months prior, were identified from the population-based National Cancer Registry. Cancer-related financial stress was assessed as impact of cancer on household ability to make ends meet and cancer-related financial strain by feelings about household financial situation since cancer diagnosis. Health-related quality of life was based on European Organisation for Research and Treatment of Cancer QLQ-C30 global health status. Logistic regression was used to identify associations between financial stress and strain and low health-related quality of life (lowest quartile, score ≤50). A total of 493 survivors participated. Overall, 41% reported cancer-related financial stress and 39% cancer-related financial strain; 32% reported both financial stress and financial strain. After adjustment for sociodemographic and clinical variables, the odds of low health-related quality of life were significantly higher in those who reported cancer-related financial stress postdiagnosis compared with those who reported no change in financial stress postcancer (OR = 2.54 (95% CI, 1.62-3.99)). The odds of low health-related quality of life were also significantly higher in those with worse financial strain postdiagnosis (OR =1.73 (95% CI, 1.09-2.72)). The OR for those with both cancer-related financial stress and financial strain was 2.59 (95% CI, 1.59-4.22). Survey responders were younger, on average, than nonresponders. Responders and nonresponders may have differed in cancer

Label-free nanoplasmonic sensing of tumor-associate autoantibodies for early diagnosis of colorectal cancer.

Science.gov (United States)

Soler, Maria; Estevez, M-Carmen; Villar-Vazquez, Roi; Casal, J Ignacio; Lechuga, Laura M

2016-08-03

Colorectal cancer is treatable and curable when detected at early stages. However there is a lack of less invasive and more specific screening and diagnosis methods which would facilitate its prompt identification. Blood circulating autoantibodies which are immediately produced by the immune system at tumor appearance have become valuable biomarkers for preclinical diagnosis of cancer. In this work, we present the rapid and label-free detection of colorectal cancer autoantibodies directly in blood serum or plasma using a recently developed nanoplasmonic biosensor. Our nanoplasmonic device offers sensitive and real-time quantification of autoantibodies with excellent selectivity and reproducibility, achieving limits of detection around 1 nM (150-160 ng mL(-1)). A preliminary evaluation of clinical samples of colorectal cancer patients has shown good correlation with ELISA. These results demonstrate the reliability of the nanobiosensor strategy and pave the way towards the achievement of a sensitive diagnostic tool for early detection of colorectal cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Science.gov (United States)

Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

2016-01-01

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the

Colorectal cancer screening

OpenAIRE

Plumb, A. A.; Halligan, S.

2015-01-01

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...

Colorectal cancer, diabetes and survival : Epidemiological insights

NARCIS (Netherlands)

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

The joint association of eating frequency and diet quality with colorectal cancer risk in the Health Professionals Follow-up Study.

Science.gov (United States)

Mekary, Rania A; Hu, Frank B; Willett, Walter C; Chiuve, Stephanie; Wu, Kana; Fuchs, Charles; Fung, Teresa T; Giovannucci, Edward

2012-04-01

The results of most case-control studies have suggested a positive association between eating frequency and colorectal cancer risk. Because no prospective cohort studies have done so to date, the authors prospectively examined this association. In 1992, eating frequency was assessed in a cohort of 34,968 US men in the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for various levels of eating frequency. Effect modifications by overall dietary quality (assessed using the Diet Approaches to Stop Hypertension score) and by factors that influence insulin resistance were further assessed. Between 1992 and 2006, a total of 583 cases of colorectal cancer were diagnosed. When comparing the highest eating frequency category (5-8 times/day) with the reference category (3 times/day), the authors found no evidence of an increased risk of colorectal cancer (multivariate relative risk = 0.88, 95% confidence interval: 0.62, 1.26) or colon cancer (multivariate relative risk = 0.78, 95% confidence interval: 0.49, 1.25). There was an implied inverse association with eating frequency among participants who had healthier diets (high Diet Approaches to Stop Hypertension score; P for interaction = 0.01), especially among men in the high-insulin-sensitivity group (body mass index (weight (kg)/height (m)(2)) frequency of healthy meals and colorectal cancer risk and in men with factors associated with higher insulin sensitivity.

Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review

Science.gov (United States)

Han, Shuwen; Gao, Jianlan; Zhou, Qing; Liu, Shanshan; Wen, Caixia

2018-01-01

Colorectal cancer is one of the most common human malignant tumors. Recent research has shown that colorectal cancer is a dysbacteriosis-induced disease; however, the role of intestinal bacteria in colorectal cancer is unclear. This review explores the role of intestinal flora in colorectal cancer. In total, 57 articles were included after identification and screening. The pertinent literature on floral metabolites in colorectal cancer from three metabolic perspectives – including carbohydrate, lipid, and amino acid metabolism – was analyzed. An association network regarding the role of intestinal flora from a metabolic perspective was constructed by analyzing the previous literature to provide direction and insight for further research on intestinal flora in colorectal cancer. PMID:29440929

Dietary Patterns and the Risk of Colorectal Cancer

OpenAIRE

Fung, Teresa T.; Brown, Lisa S.

2012-01-01

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 ...

Nutritional status assessment in colorectal cancer patients.

Science.gov (United States)

Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda

2013-01-01

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.

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

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Erbao Chen

2018-01-01

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.

Consumption of dairy products and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC.

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Neil Murphy

Full Text Available Prospective studies have consistently reported lower colorectal cancer risks associated with higher intakes of total dairy products, total milk and dietary calcium. However, less is known about whether the inverse associations vary for individual dairy products with differing fat contents.In the European Prospective Investigation into Cancer and Nutrition (EPIC, we investigated the associations between intakes of total milk and milk subtypes (whole-fat, semi-skimmed and skimmed, yoghurt, cheese, and dietary calcium with colorectal cancer risk amongst 477,122 men and women. Dietary questionnaires were administered at baseline. Multivariable hazard ratios (HRs and 95% confidence intervals (CIs were estimated using Cox proportional hazards models, adjusted for relevant confounding variables.During the mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred. After multivariable adjustments, total milk consumption was inversely associated with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89-0.98. Similar inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI: 0.82-0.99 and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79-1.02 in the multivariable models. Inverse associations were observed for cheese and yoghurt in the categorical models; although in the linear models, these associations were non-significant. Dietary calcium was inversely associated with colorectal cancer risk (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99; this association was limited to dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99, with no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00, 95% CI: 0.81-1.24.Our results strengthen the evidence for a possible protective role of dairy products on colorectal cancer risk. The inverse associations we observed did not differ by the fat content of the dairy products considered.

Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice.

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Kim, Han-Byul; Kim, Minchul; Park, Young-Soo; Park, Intae; Kim, Tackhoon; Yang, Sung-Yeun; Cho, Charles J; Hwang, DaeHee; Jung, Jin-Hak; Markowitz, Sanford D; Hwang, Sung Wook; Yang, Suk-Kyun; Lim, Dae-Sik; Myung, Seung-Jae

2017-02-01

Prostaglandin E 2 (PGE 2 ) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE 2 signaling pathway that contribute to tumor formation. We investigated whether yes-associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE 2 function. DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE 2 , with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse-transcription polymerase chain reaction, transcriptional reporter, and proliferation assays. Dextran sodium sulfate (DSS) was given to induce colitis in C57/BL6 (control) mice, as well as in mice with disruption of the hydroxyprostaglandin dehydrogenase 15 gene (15-PGDH-knockout mice), Yap1 gene (YAP-knockout mice), and double-knockout mice. Some mice also were given indomethacin to block PGE 2 synthesis. 15-PGDH knockout mice were crossed with mice with intestine-specific disruption of the salvador family WW domain containing 1 gene (Sav1), which encodes an activator of Hippo signaling. We performed immunohistochemical analyses of colon biopsy samples from 26 patients with colitis-associated cancer and 51 age-and sex-matched patients with colorectal cancer (without colitis). Incubation of colon cancer cell lines with PGE 2 led to phosphorylation of cyclic adenosine monophosphate-responsive element binding protein 1 and increased levels of YAP1 messenger RNA, protein, and YAP1 transcriptional activity. This led to increased transcription of the prostaglandin-endoperoxide synthase 2 gene (PTGS2 or cyclooxygenase 2) and prostaglandin E-receptor 4 gene (PTGER4 or EP4). Incubation with PGE 2 promoted proliferation of colon cancer cell lines, but not cells with knockdown of YAP1. Control mice

Dietary calcium intake and the risk of colorectal cancer: a case control study

OpenAIRE

Han, Changwoo; Shin, Aesun; Lee, Jeonghee; Lee, Jeeyoo; Park, Ji Won; Oh, Jae Hwan; Kim, Jeongseon

2015-01-01

Background High intake of dietary calcium has been thought to be a protective factor against colorectal cancer. To explore the dose-response relationship in the associations between dietary calcium intake and colorectal cancer risk by cancer location, we conducted a case-control study among Korean population, whose dietary calcium intake levels are relatively low. Methods The colorectal cancer cases and controls were recruited from the National Cancer Center in Korea between August 2010 and A...

Serum carotenoids and colorectal cancer risk: A case-control study in Guangdong, China.

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Huang, Jing; Lu, Min-Shan; Fang, Yu-Jing; Xu, Ming; Huang, Wu-Qing; Pan, Zhi-Zhong; Chen, Yu-Ming; Zhang, Cai-Xia

2017-10-01

Previous epidemiological studies on the association between circulating carotenoids and the risk of colorectal cancer drew inconclusive conclusions. This study aimed to examine serum carotenoids in relation to colorectal cancer risk in a Chinese population. One case-control study beginning from July 2010, consecutively recruited 538 eligible colorectal cancer cases and 564 age (5-year interval) and sex frequency-matched controls. Serum levels of α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin were detected by HPLC. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI) after adjusting for various confounders. Serum levels of α-carotene, β-cryptoxanthin and lycopene were found to be inversely associated with colorectal cancer risk. The adjusted ORs of the highest quartile relative to the lowest quartile serum level were 0.49 (95% CIs 0.33-0.72) for α-carotene, 0.44 (95% CIs 0.29-0.66) for β-cryptoxanthin, and 0.36 (95% CIs 0.24-0.54) for lycopene, respectively. The association between serum β-carotene, lutein/zeaxanthin and colorectal cancer risk was not statistically significant. The results indicated that the incidence of colorectal cancer was associated with lower serum levels of α-carotene, β-cryptoxanthin and lycopene among Chinese population residing in Guangdong. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Model selection approach suggests causal association between 25-hydroxyvitamin D and colorectal cancer.

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Lina Zgaga

Full Text Available Vitamin D deficiency has been associated with increased risk of colorectal cancer (CRC, but causal relationship has not yet been confirmed. We investigate the direction of causation between vitamin D and CRC by extending the conventional approaches to allow pleiotropic relationships and by explicitly modelling unmeasured confounders.Plasma 25-hydroxyvitamin D (25-OHD, genetic variants associated with 25-OHD and CRC, and other relevant information was available for 2645 individuals (1057 CRC cases and 1588 controls and included in the model. We investigate whether 25-OHD is likely to be causally associated with CRC, or vice versa, by selecting the best modelling hypothesis according to Bayesian predictive scores. We examine consistency for a range of prior assumptions.Model comparison showed preference for the causal association between low 25-OHD and CRC over the reverse causal hypothesis. This was confirmed for posterior mean deviances obtained for both models (11.5 natural log units in favour of the causal model, and also for deviance information criteria (DIC computed for a range of prior distributions. Overall, models ignoring hidden confounding or pleiotropy had significantly poorer DIC scores.Results suggest causal association between 25-OHD and colorectal cancer, and support the need for randomised clinical trials for further confirmations.

Bone morphogenetic protein signalling in colorectal cancer

NARCIS (Netherlands)

Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.

2008-01-01

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

DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers

DEFF Research Database (Denmark)

Jorissen, Robert N; Lipton, Lara; Gibbs, Peter

2008-01-01

Purpose: About 15% of colorectal cancers harbor microsatellite instability (MSI). MSI-associated gene expression changes have been identified in colorectal cancers, but little overlap exists between signatures hindering an assessment of overall consistency. Little is known about the causes...... and downstream effects of differential gene expression. Experimental Design: DNA microarray data on 89 MSI and 140 microsatellite-stable (MSS) colorectal cancers from this study and 58 MSI and 77 MSS cases from three published reports were randomly divided into test and training sets. MSI-associated gene......-number data. Results: MSI-associated gene expression changes in colorectal cancers were found to be highly consistent across multiple studies of primary tumors and cancer cell lines from patients of different ethnicities (P

The association between location, age and advanced colorectal adenoma characteristics

DEFF Research Database (Denmark)

Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

2017-01-01

PURPOSE: Evidence supports an association between certain colorectal adenoma characteristics and predisposition to cancer. The association between anatomical location of colorectal adenoma, age and advanced adenomas needs attention. The objective of this study was to evaluate the possible....... Inclusion criteria for patients were one adenoma of >1 cm in diameter or multiple adenomas of any size, or an adenoma of any size and familial disposition for colorectal cancer. Multivariate regression and propensity score-matched analyses were used to correlate location of adenomas and age with advanced...... adenoma features. RESULTS: In this study, 2149 adenomas were removed in 1215 patients. Advanced colorectal adenomas primarily occurred in the anal part of the colon. Older age was associated with more adenomas and more oral occurrence of adenomas, as well as a higher risk of advanced adenomas...

Multiple Regression Analysis of mRNA-miRNA Associations in Colorectal Cancer Pathway

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Wang, Fengfeng; Wong, S. C. Cesar; Chan, Lawrence W. C.; Cho, William C. S.; Yip, S. P.; Yung, Benjamin Y. M.

2014-01-01

Background. MicroRNA (miRNA) is a short and endogenous RNA molecule that regulates posttranscriptional gene expression. It is an important factor for tumorigenesis of colorectal cancer (CRC), and a potential biomarker for diagnosis, prognosis, and therapy of CRC. Our objective is to identify the related miRNAs and their associations with genes frequently involved in CRC microsatellite instability (MSI) and chromosomal instability (CIN) signaling pathways. Results. A regression model was adopted to identify the significantly associated miRNAs targeting a set of candidate genes frequently involved in colorectal cancer MSI and CIN pathways. Multiple linear regression analysis was used to construct the model and find the significant mRNA-miRNA associations. We identified three significantly associated mRNA-miRNA pairs: BCL2 was positively associated with miR-16 and SMAD4 was positively associated with miR-567 in the CRC tissue, while MSH6 was positively associated with miR-142-5p in the normal tissue. As for the whole model, BCL2 and SMAD4 models were not significant, and MSH6 model was significant. The significant associations were different in the normal and the CRC tissues. Conclusion. Our results have laid down a solid foundation in exploration of novel CRC mechanisms, and identification of miRNA roles as oncomirs or tumor suppressor mirs in CRC. PMID:24895601

Brain metastasis from colorectal cancer

International Nuclear Information System (INIS)

Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

2007-01-01

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)

Colorectal cancer presenting as bone metastasis

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M C Suresh Babu

2017-01-01

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.

Colorectal tuberculosis

International Nuclear Information System (INIS)

Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.

2003-01-01

Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

Galectin-3 expression in colorectal cancer and its correlation with clinical pathological characteristics and prognosis

OpenAIRE

Tao Liu; Jin Li; Dechun Li; Hongqiang Yang; Changhua Kou; Guijun Lei

2017-01-01

Abstract Objective 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. Methods An immunohistochemistry assay was used to test the expression levels of galectin-3 in cancer tissues of 61 colorectal cancer cases and in normal intestinal tissues adjacent to the cancer tissues of 23 cases. The associations between protein expression levels of gal...

The relationship between nut intake and risk of colorectal cancer: a case control study.

Science.gov (United States)

Lee, Jeeyoo; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

2018-03-07

Nut consumption is known to reduce the risk of obesity, diabetes mellitus, and cardiovascular disease. However, in previous studies, portion sizes and categories of nut consumption have varied, and few studies have assessed the association between colorectal cancer risk and nut consumption. In this study, we investigated the relationship between nut consumption and colorectal cancer risk. A case-control study was conducted among 923 colorectal cancer patients and 1846 controls recruited from the National Cancer Center in Korea. Information on dietary intake was collected using a semi-quantitative food frequency questionnaire with 106 items, including peanuts, pine nuts, and almonds (as 1 food item). Nut consumption was categorized as none, consumption and colorectal cancer risk, and a polytomous logistic regression model was used for sub-site analyses. High nut consumption was strongly associated with reduced risk of colorectal cancer among women (adjusted ORs: 0.30, 95%CI: 0.15-0.60 for the ≥3 servings per week group vs. none). A similar inverse association was observed for men (adjusted ORs: 0.28, 95% CI: 0.17-0.47). In sub-site analyses, adjusted ORs (95% CIs) comparing the ≥3 servings per week group vs none were 0.25 (0.09-0.70) for proximal colon cancer, 0.39 (0.19-0.80) for distal colon cancer, and 0.23 (0.12-0.46) for rectal cancer among men. An inverse association was also found among women for distal colon cancer (OR: 0.13, 95% CI: 0.04-0.48) and rectal cancer (OR: 0.40, 95% CI: 0.17-0.95). We found a statistically significant association between high frequency of nut consumption and reduced risk of colorectal cancer. This association was observed for all sub-sites of the colon and rectum among both men and women, with the exception of proximal colon cancer for women.

Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

Science.gov (United States)

Hung, Rayjean J; Ulrich, Cornelia M; Goode, Ellen L; Brhane, Yonathan; Muir, Kenneth; Chan, Andrew T; Marchand, Loic Le; Schildkraut, Joellen; Witte, John S; Eeles, Rosalind; Boffetta, Paolo; Spitz, Margaret R; Poirier, Julia G; Rider, David N; Fridley, Brooke L; Chen, Zhihua; Haiman, Christopher; Schumacher, Fredrick; Easton, Douglas F; Landi, Maria Teresa; Brennan, Paul; Houlston, Richard; Christiani, David C; Field, John K; Bickeböller, Heike; Risch, Angela; Kote-Jarai, Zsofia; Wiklund, Fredrik; Grönberg, Henrik; Chanock, Stephen; Berndt, Sonja I; Kraft, Peter; Lindström, Sara; Al Olama, Ali Amin; Song, Honglin; Phelan, Catherine; Wentzensen, Nicholas; Peters, Ulrike; Slattery, Martha L; Sellers, Thomas A; Casey, Graham; Gruber, Stephen B; Hunter, David J; Amos, Christopher I; Henderson, Brian

2015-11-01

Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

Increased risk of colorectal cancer in type 2 diabetes is independent of diet quality.

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Soghra Jarvandi

Full Text Available Poor diet increases the risk of both colorectal cancer and type 2 diabetes. We investigated the role of diet in the association between diabetes and colorectal cancer.We analyzed data from 484,020 individuals, aged 50-71 years who participated in the prospective National Institutes of Health-AARP Diet and Health Study and were cancer free at baseline (1995-1996. History of diabetes was self-reported. Diet quality was measured with the Healthy Eating Index-2005 (HEI-2005, using a self-administered food-frequency questionnaire. Cox regression models were constructed to estimate the hazard ratios (HR and 95% confidence intervals (CI of first primary incident colorectal cancer, overall and by anatomical location.During an average follow-up of 9.2 years, we identified 7,598 new cases of colorectal cancer. After controlling for non-dietary confounders, diabetes was associated with increased risk of colorectal cancer (HR 1.27, 95% CI: 1.18, 1.36. Further adjustment for diet quality did not attenuate this association. Diabetes was associated with a HR of 1.23 (95% CI: 1.07, 1.40 in individuals with good diet (quartile 4 of HEI-2005 and 1.58 (95% CI: 1.34, 1.86 in those with poor diet (quartile 1 of HEI-2005, compared to those with no diabetes and good diet. Moreover, diabetes was associated with a stronger risk of proximal than distal colon cancer (HR: 1.33 vs. HR: 1.20, while poor diet was associated with a weaker risk of proximal colon cancer (HR: 1.18 vs. HR: 1.46.Diabetes and poor diet, independently and additively are associated with the increased risk of colorectal cancer.

Colorectal Cancer: What You Should Know

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... 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 ...

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans.

Science.gov (United States)

Sanapareddy, Nina; Legge, Ryan M; Jovov, Biljana; McCoy, Amber; Burcal, Lauren; Araujo-Perez, Felix; Randall, Thomas A; Galanko, Joseph; Benson, Andrew; Sandler, Robert S; Rawls, John F; Abdo, Zaid; Fodor, Anthony A; Keku, Temitope O

2012-10-01

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn's disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1-V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria from 87 taxa than controls; only 5 taxa were more abundant in control samples. The magnitude of the differences in the distal gut microbiota between patients with adenomas and controls was more pronounced than that of any other clinical parameters including obesity, diet or family history of CRC. This suggests that sequence analysis of the microbiota could be used to identify patients at risk for developing adenomas.

OTX1 promotes colorectal cancer progression through epithelial-mesenchymal transition

International Nuclear Information System (INIS)

Yu, Kun; Cai, Xin-Yi; Li, Qiang; Yang, Zhi-Bin; Xiong, Wei; Shen, Tao; Wang, Wei-Ya; Li, Yun-Feng

2014-01-01

Highlights: • OTX1 is overexpression in colorectal cancer tissues. • Overexpression of OTX1 promotes colorectal cancer cell proliferation and invasion in vitro and tumor growth in vivo. • Depletion of OTX1 inhibits colorectal cancer cell proliferation and invasion in vitro. • Overexpression of OTX1 is linked to the EMT-like phenotype. - Abstract: Orthodenticle homeobox 1 (OTX1), a transcription factor containing a bicoid-like homeodomain, plays a role in brain and sensory organ development. In this study, we report that OTX1 is overexpressed in human colorectal cancer (CRC) and OTX1 overexpression is associated with higher stage. Functional analyses reveal that overexpression of OTX1 results in accumulation of CRC cell proliferation and invasion in vitro and tumor growth in vivo, whereas ablation of OTX1 expression significantly inhibits the proliferative and invasive capability of CRC cells in vitro. Together, our results indicate that OTX1 is involved in human colon carcinogenesis and may serve as a potential therapeutic target for human colorectal cancer

OTX1 promotes colorectal cancer progression through epithelial-mesenchymal transition

Energy Technology Data Exchange (ETDEWEB)

Yu, Kun; Cai, Xin-Yi; Li, Qiang; Yang, Zhi-Bin; Xiong, Wei; Shen, Tao; Wang, Wei-Ya; Li, Yun-Feng, E-mail: ynsliyunfeng@163.com

2014-01-31

Highlights: • OTX1 is overexpression in colorectal cancer tissues. • Overexpression of OTX1 promotes colorectal cancer cell proliferation and invasion in vitro and tumor growth in vivo. • Depletion of OTX1 inhibits colorectal cancer cell proliferation and invasion in vitro. • Overexpression of OTX1 is linked to the EMT-like phenotype. - Abstract: Orthodenticle homeobox 1 (OTX1), a transcription factor containing a bicoid-like homeodomain, plays a role in brain and sensory organ development. In this study, we report that OTX1 is overexpressed in human colorectal cancer (CRC) and OTX1 overexpression is associated with higher stage. Functional analyses reveal that overexpression of OTX1 results in accumulation of CRC cell proliferation and invasion in vitro and tumor growth in vivo, whereas ablation of OTX1 expression significantly inhibits the proliferative and invasive capability of CRC cells in vitro. Together, our results indicate that OTX1 is involved in human colon carcinogenesis and may serve as a potential therapeutic target for human colorectal cancer.

Colorectal carcinogenesis: Review of human and experimental animal studies

Directory of Open Access Journals (Sweden)

Tanaka Takuji

2009-01-01

Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

DNA Fingerprinting Abnormalities Can Distinguish Ulcerative Colitis Patients with Dysplasia and Cancer from Those Who Are Dysplasia/Cancer-Free

Science.gov (United States)

Chen, Ru; Rabinovitch, Peter S.; Crispin, David A.; Emond, Mary J.; Koprowicz, Kent M.; Bronner, Mary P.; Brentnall, Teresa A.

2003-01-01

Patients with extensive ulcerative colitis (UC) of longer than 8 years duration are at high risk for the development of colorectal cancer. The cancers in these patients appear to develop in a stepwise manner with progressive histological changes from negative for dysplasia → indefinite for dysplasia → dysplasia → cancer. The aim of this study was to determine the timing and extent of genomic instability in the progression of UC dysplasia and cancer. Using two polymerase chain reaction (PCR)-based DNA fingerprinting methods, arbitrarily primed PCR and intersimple sequence repeat PCR, we assessed DNA sequence variation in biopsies across the spectrum of cancerous, dysplastic, and nondysplastic mucosa. UC patients with dysplasia/cancer had substantial genomic instability in both their dysplastic and nondysplastic colonic mucosa, whereas instability was not present in the majority of UC patients without dysplasia/cancer. The degree of instability in nondysplastic tissue was similar to that of dysplastic/cancerous mucosa from the same patient, suggesting that this instability was widespread and reached the maximum level early in neoplastic progression. These results suggest that UC patients who develop dysplasia or cancer have an underlying process of genomic instability in their colonic mucosa whereas UC patients who are dysplasia-free do not. PMID:12547724

Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

Science.gov (United States)

Rubio, Carlos A; DE Petris, Giovanni; Puppa, Giacomo

2018-02-01

In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARgamma.

Science.gov (United States)

Evans, Nicholas P; Misyak, Sarah A; Schmelz, Eva M; Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-03-01

Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPARgamma in immune and epithelial cells and PPARgamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPARgamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPARgamma-expressing floxed mice but not in the tissue-specific PPARgamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPARgamma-expressing, but not in the tissue-specific, PPARgamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPARgamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPARgamma-dependent mechanism.

Meat consumption and risk of colorectal cancer in Japan: the Miyagi Cohort Study.

Science.gov (United States)

Sato, Yuki; Nakaya, Naoki; Kuriyama, Shinichi; Nishino, Yoshikazu; Tsubono, Yoshitaka; Tsuji, Ichiro

2006-06-01

The association between meat consumption and risk of colorectal cancer has been controversial. We examined this question in a large prospective cohort study in Japan. From June through August 1990, 47,605 residents, aged 40-64 years, of Miyagi Prefecture in northern Japan completed a self-administered questionnaire, including a food frequency questionnaire. In the study population, we observed 474 incident cases of colorectal cancer during 11 years of follow-up, to March 2001. We used the Cox proportional hazards model to estimate the relative risk of colorectal cancer (colorectum, colon, rectum and proximal colon and distal colon) according to each of the categories of meat intake (total meat, beef, pork, ham or sausage, chicken and liver), with adjustment for sex, age and other potentially confounding variables. The multivariate relative risk of colorectal cancer in the highest category of total meat consumption compared with the lowest was 1.14 [95% confidence interval (CI)=0.85-1.53; P-trend=0.22]. We also found no significant association between total meat consumption and the risk of sub-site of colorectal cancer. In conclusion, our data do not support the hypothesis that meat consumption is a risk factor for colorectal cancer.

The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands

NARCIS (Netherlands)

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.

1990-01-01

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).

Fish consumption and the risk of colorectal cancer: the Ohsaki Cohort Study.

Science.gov (United States)

Sugawara, Y; Kuriyama, S; Kakizaki, M; Nagai, M; Ohmori-Matsuda, K; Sone, T; Hozawa, A; Nishino, Y; Tsuji, I

2009-09-01

Evidence from laboratory and animal studies suggests that high fish consumption may reduce the risk of colorectal cancer, but the results of studies in humans have been inconsistent. The objective of this study was to prospectively examine the association between fish consumption and the risk of colorectal cancer incidence in Japan, where fish is widely consumed. We analysed data from 39 498 men and women registered in the Ohsaki National Health Insurance Cohort Study who were 40-79 years old and free of cancer at the baseline. Fish consumption was assessed at the baseline using a self-administered food frequency questionnaire. During 9 years of follow-up, we identified 566 incident cases of colorectal cancer (379 men and 187 women). The hazard ratios and 95% confidence intervals (CIs) for colorectal cancer incidence in the highest quartile of fish consumption compared with the lowest quartile were 1.07 (95% CIs; 0.78-1.46, P-trend=0.43) for men, and 0.96 (95% CIs; 0.61-1.53, P-trend=0.69) for women. The results of this prospective cohort study revealed no association between fish consumption and the risk of colorectal cancer.

The Synchronous Prevalence of Colorectal Neoplasms in Patients with Stomach Cancer

OpenAIRE

Lee, Sang Su; Jung, Woon Tae; Kim, Cha Young; Ha, Chang Yoon; Min, Hyun Ju; Kim, Hyun Jin; Kim, Tae Hyo

2011-01-01

Purpose The association between stomach cancer and colorectal cancer is controversial. The purpose of this study was to determine the synchronous prevalence of colorectal neoplasms in patients with stomach cancer. Methods A total of 123 patients with stomach cancer (86 male) and 246 consecutive, age- and sex-matched persons without stomach cancer were analyzed from July 2005 to June 2010. All of them underwent colonoscopy within 6 months after undergoing gastroscopy. Results The prevalence of...

MicroRNA-96 Promotes Tumor Invasion in Colorectal Cancer via RECK.

Science.gov (United States)

Iseki, Yasuhito; Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Hirakawa, Kosei; Ohira, Masaichi

2018-04-01

miR-96 is reported to inhibit reversion cysteine-rich Kazal motif (RECK), which is associated with tumor invasion, in solid cancer types (e.g. breast cancer, non-small cell lung cancer, esophageal cancer). The purpose of this study is to clarify whether miR-96 is similarly associated with tumor invasion in colorectal cancer. We performed western blotting to investigate the expression of RECK when miR-96 mimics or inhibitors were transferred into HCT-116 colorectal cancer cells. The RECK mRNA level was assessed by a reverse transcription polymerase chain reaction. An invasion assay was used to evaluate tumor invasion. The expression of RECK was inhibited by the transfection of miR-96 mimics. RECK mRNA level was reduced by miR-96 mimics and increased by miR-96 inhibitor. In the invasion assay, miR-96 mimics were shown to promote tumor invasion. miR-96 may be associated with tumor invasion through inhibition of RECK expression in colorectal cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Variation in the Vitamin D Receptor Gene is not Associated with Risk of Colorectal Cancer in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Hughes, D. J.; Hlavatá, I.; Souček, P.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Jenab, M.; Vodička, Pavel

2011-01-01

Roč. 42, č. 3 (2011), s. 149-154 ISSN 1941-6628 Institutional research plan: CEZ:AV0Z50390512 Keywords : colorectal cancer * cancer genetics * association study Subject RIV: EB - Genetics ; Molecular Biology

MIS in the management of colon and rectal cancer: consensus meeting of the Colorectal Cancer Association of Canada.

Science.gov (United States)

Schlachta, Christopher M; Ashamalla, Shady; Smith, Andy

2013-11-01

A consensus conference on the role of minimally invasive surgery (MIS) in the management of colon and rectal cancer was convened by the Colorectal Cancer Association of Canada in Toronto on April 18, 2012. This is a report of the consensus of an invited group of Canadian experts in MIS and surgery of the colon and rectum that addresses the role this technology should play in treatment and also considers advocacy and resources.

Radioimmunodetection of colorectal cancer

International Nuclear Information System (INIS)

Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.

1980-01-01

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

Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

Science.gov (United States)

Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

2016-08-15

A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

Colorectal Cancer Screening: A Guide to the Guidelines

Directory of Open Access Journals (Sweden)

Douglas K Rex

1999-01-01

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.

Predictors of advanced colorectal neoplasia for colorectal cancer screening.

Science.gov (United States)

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

2014-05-01

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.

Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease

DEFF Research Database (Denmark)

Munkholm, P

2003-01-01

Although colorectal cancer (CRC), complicating ulcerative colitis and Crohn's disease, only accounts for 1-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 15% of all deaths in inflammatory bowel disease (IBD...... of symptoms, and extent of the disease, with pancolitis having a more severe inflammation burden and risk of the dysplasia-carcinoma cascade. Considering the chronic nature of the disease, it is remarkable that there is such a low incidence of CRC in some of the population-based studies, and possible...... in Crohn's disease, the number was significantly increased in relation to the expected number....

Peritumoral eosinophils predict recurrence in colorectal cancer.

Science.gov (United States)

Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord

2015-03-01

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

Carbohydrate, dietary glycaemic index and glycaemic load, and colorectal cancer risk: a case-control study in China.