Salvi, S; Conteduca, V; Gurioli, G; Calistri, D; Casadio, V; De Giorgi, U
In the last few years, the presence of single nucleotide polymorphisms (SNPs) has been investigated in many tumors as predictor of disease aggressiveness and clinical outcome. We searched for relevant articles from 1998 to 2015 about the impact of SNPs in prostate cancer. Particularly, in this article, we review the pathogenetic, prognostic and predictive significance of gene polymorphisms in prostate tumor, providing a brief overview of studies in which the possible role of genetic variants was investigated in clinical settings. Because conflicting results often emerge about the impact of gene polymorphisms in prostate cancer, further larger studies are warranted in order to introduce gene polymorphism into clinical practice as biomarkers. PMID:26518421
Expert-reviewed information summary in which the features of hereditary cancer and the structure and content of other PDQ cancer genetics summaries are described. The summary also contains an extensive list of genetics resources available online.
Renal cell carcinoma is a group of malignancies arising from the epithelium of the renal tubules. The pattern of somatic mutations in kidney tumors has been extensively investigated. In the current 2004 WHO classification, the molecular background of a renal tumor has become, in addition to histopathology, a major criterion for tumor classification. The goal of this review is to discuss morphology and genetics of adult renal epithelial cancer included in the 2004 WHO classification and to men...
... Prevention Overview–for health professionals Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, ...
... Treatment Genetics of Colorectal Cancer Age and family history can affect the risk of rectal cancer. Anything ... to flow from the body to a collection bag. After the cancer is removed, the surgeon will ...
LI Marilyn; ALBERTSON Donna
The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.
... enlarged thyroid). Having a family history of thyroid disease or thyroid cancer. Having certain genetic conditions such as familial medullary thyroid cancer (FMTC), multiple endocrine neoplasia type 2A ...
... Other less common types of breast cancer include: Medullary Mucinous Tubular Metaplastic Papillary breast cancer Inflammatory breast cancer is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers. Paget’s disease is a type of cancer that begins in ...
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... Cancers of Childhood Treatment Childhood Cancer Genomics Research Childhood Cancer Survivor Study: An Overview In 2016, it ... Late Effects of Treatment for Childhood Cancer .) The Childhood Cancer Survivor Study ( CCSS ), funded by the National ...
Bogaert, Julie; Prenen, Hans
Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764
... lung cancer and secondhand tobacco smoke , outdoor air pollution, and asbestos . Drinking water that contains a large amount of arsenic has been linked to skin , bladder, and lung cancers. Studies have been done ...
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... a roadmap to this full guide. About the vulva The vulva is a woman’s external genitalia and is made ... labia majora and labia minora. Cancer of the vulva occurs most often in or on the labia. ...
This summary is to provide the reader with a brief overview of the key concepts relating to epidemiology and etiology; clinical presentation and patterns of spread; Canadian guidelines for management; prognosis; and current Canadian screening recommendations in the diagnosis and treatment of breast cancer. This information will enable the reader to have the appropriate background knowledge before delving into the subsequent articles in this special CJMRT breast cancer edition. A variety of references have been provided for readers who are interested in more than a skeleton version of the current literature. (author)
Full Text Available Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16INK4, DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers.
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Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlig...
Rustgi, Anil K.
This review by Rustgi elaborates on the known genetic syndromes that underlie familial pancreatic cancer. It aims to delineate the subtypes of syndromic hereditary pancreatic cancer in which germline genetic mutations have been identified and nonsyndromic familial pancreatic cancer in which genetic information is emerging.
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Cruz, Araceli Lantigua
This brief report provides an overview of the history and current status of genetic services in Cuba. In 1971, the University of Medical Sciences of Havana began to train doctors in medical genetics according to the medicine development plan in Cuba. With the aim of introducing genetic services to the population, two main issues were identified: the impact of neural tube defects as a cause of infantile mortality, and a founder effect resulting in a high frequency of sickle cell anemia, which increased the mortality rate and impacted the quality of peoples' lives. The impact of consanguinity is variable; it depends on the isolation of the population, with rates of 1 to 11% in different regions for first and second cousin marriages. From 1981, the services of medical genetics began to expand to the entire country, according to a government directive, and the need to design a program for the specialty became evident. From 1995 to 2000, two Masters-level programs were designed by professors of the Department of Medical Genetics, University of Medical Sciences of Havana, and authorized by the Ministry of Higher Education. One program in medical genetics was designed for physicians with other specialties, and the second program was designed to train professionals to become genetic counselors. The majority of graduates from the latter program are working at the primary level of healthcare. PMID:23934326
... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...
... Cancer Treatment Anal Cancer Prevention Research Anal Cancer Treatment (PDQ®)–Patient Version General Information About Anal Cancer ... factors affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on ...
... Cancer Treatment Bladder Cancer Screening Research Bladder Cancer Treatment (PDQ®)–Patient Version General Information About Bladder Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on ...
... Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...
... Cancer Prevention Cervical Cancer Screening Research Cervical Cancer Treatment (PDQ®)–Patient Version General Information About Cervical Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery) depends on ...
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... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...
Prostate cancer is a major health burden throughout the world, yet the etiology of prostate cancer is poorly understood. Evidence has accumulated supporting the existence of a hereditary form of this disease. Improved understanding of the genetic mechanisms underlying the development and progression of prostate cancer would be a major advance for improved prevention, detection and treatment strategies. This thesis evaluates different aspects of the genetic epidemiology of prostate cancer. In ...
... Cancer Overview Risk of Hereditary Cancer Hereditary Breast & Ovarian Cancer Colon Cancer Lynch Syndrome Cancer Counseling Other Hereditary Cancer Syndromes Cancer Support Organizations Our Statement on BRCA and Genetic Screening Health & Genetics Through a Jewish Lens Genetic Carrier ...
... Disease Control and Prevention Lynch Syndrome, Genetics Home Reference, U.S. National Library of Medicine Cancer Genetic Services Directory, National Cancer Institute Find-A-Counselor, National ...
Ghaleb Elyamany; Ali Mattar Alzahrani; Eman Bukhary
Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Emerging data have enhanced our understanding of cancer-associated thrombosis, a major cause of morbidity and mortality in patients with cancer. In addition to VTE, arterial occlusion with stroke and anginal symptoms is relatively common among cancer patients, and is possibly related to genetic predisposition. Several risk factors for developing venous thrombosis usually coexist in cancer patients includ...
... radiation therapy . Mohs microsurgery . A clinical trial of laser therapy . Check the list of NCI-supported cancer clinical ... nodes in the groin ). External or internal radiation therapy followed by ... clinical trial of laser surgery . Check the list of NCI-supported cancer ...
Lim, Gerard Chin Chye
The problem of cancer in Malaysia is a growing one. It is now the fourth leading cause of death among medically certified deaths. Cancer of the lung is the most common killer among malignancies. It is estimated that the annual incidence of cancer is 30 000. The majority of patients are found at a late stage of the disease. The National Cancer Control Program aims to reduce the incidence and mortality of cancer and to improve the quality of life of cancer patients. Policies encompass prevention, early diagnosis, treatment, palliative care and rehabilitation. The program for prevention includes an anti-smoking campaign and immunization of babies against hepatitis B. Papanicolaou's smear and breast self-examination are among efforts for the early detection of cancer. Public education and the promotion of healthy lifestyles have been actively carried out. Facilities for treatment and palliative care are being developed further. Networks between the public and private sectors and non-governmental organizations have been on-going. Apart from the establishment and upgrading of treatment facilities, the need for training of skilled staff in the treatment of cancer is highlighted. PMID:11959876
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... Jewish heritage and people of Norwegian, Icelandic, or Dutch ancestry. Related Information What information about a genetic ... an increased likelihood of developing cancer, not the disease itself. Not all people who inherit mutations in ...
... miscarriage (premature birth of a fetus that cannot survive). Women who were exposed to DES before birth ... to relieve symptoms and improve quality of life . Chemotherapy Chemotherapy is a cancer treatment that uses drugs ...
... and nonseminomas . These 2 types grow and spread differently and are treated differently. Nonseminomas tend to grow and spread more quickly ... trials is available from the NCI website . To Learn More About Testicular Cancer For more information from ...
... trials is available from the NCI website . Locally Advanced or Inflammatory Breast Cancer Treatment of locally advanced ... NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an ...
... through the outer layers as it grows. Being female can increase the risk of developing gallbladder cancer. Anything that increases your chance of getting a disease is called a risk factor . Having a risk factor does not mean that ...
... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and stomach, and ... tissues so they can be viewed under a microscope to check for signs of cancer. A biopsy ...
... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and stomach, and ... remove tissue samples, which are checked under a microscope for signs of cancer. When the esophagus and ...
... The surgeon may use part of the small intestine to make a tube that passes urine through an opening ( stoma ). This is called an ostomy or urostomy . If ... surgeon may also use part of the small intestine to make a new storage pouch ( continent ... the urine through a stoma. Even if the doctor removes all the cancer ...
... around it. Sometimes lymph nodes , half of the thyroid gland on the same side of the body as the cancer, and muscles, tissues , and a nerve in the neck are also removed. Tumor debulking : A surgical procedure in which as much ...
... to a gene mutation, such as breast or ovarian cancer Your family members had cancer at a younger age than normal for that type of cancer You have had cancer screening results that may point to genetic causes Family ...
The advent of genetic testing has made a dramatic impact on the management of individuals with inherited susceptibility to cancer and their relatives. Genetic counsel ing, with or without testing, is warranted when clues to familial cancer are recognized. Today, genetic testing for classic cancer genetic syndromes is now the standard of care, and has been complemented by genetic testing for other situations commonly encountered in clinical practice. Genetic testing for colorectal cancer, breast cancer, kidney cancer, thyroid cancer, melanoma, and pancreatic cancer raise important issues about the parameters for testing. Genetic cancer risk assessment can lead to measurable reductions in morbidity and mortality through strategies that rely on surveillance, chemo prevention, and risk-reducing surgery
D. K. V. Prasad
Full Text Available Idiopathic generalized epilepsy (IGE is a common type of epilepsy. Strong support for a genetic role in IGE comes from twin and family studies. Several subtypes of IGE have been reported but families often have members affected with different subtypes. Major advances have been made in the understanding of genetic basis of monogenic inherited epilepsies. However, most IGEs are complex genetic diseases and some susceptible IGE genes are shared across subtypes that determine subtypes in specific combinations. The high throughput technologies like deoxyribonucleic acid microarrays and sequencing technologies have the potential to identify causative genes or loci in non-familial cases.
Full Text Available Stroke or "brain attack" is a complex disease caused by a combination of multiple risk factors. It has major social and economic consequences. Various epidemiological studies in families and twins have revealed that there is a genetic component to stroke risk. Stroke may be the outcome of single gene disorders or more commonly, a polygenic multifactorial disease. Mutations in several candidate genes have been found to be associated with stroke. However, association studies in population-based samples have failed to identify reliable disease markers. The publication of the "Human Genome Project" has indeed improved our knowledge about the potential role of genetics in complex disorders including stroke. Rapidly expanding field of genetics is in a state of transforming medicine into a new kind in future, the individualized medicine, using tailor made drugs according to the genetic makeup of the individuals. However, this involves integrating genome wide genetic information with medical information. The first genome wide association study on ischemic stroke has been published recently. Further studies will hopefully tell us how far the genetic information will assist us to tailor clinical and therapeutic decisions to an individual′s genotype.
Breast cancer accounts for one third of all female cancer cases worldwide. A hereditary component accounts for 10-15% of all breast and ovarian cancer cases. The overall aim of this thesis is to evaluate and improve genetic diagnostic and genetic counseling in hereditary cancer patients. A total of 215 counselees were enrolled to a questionnaire study which aimed to conceptualize risk perception and worry for cancer before and one week after initial oncogenetic counseling and one year a...
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Francesco Camastra; Maria Donata Di Taranto; Antonino Staiano
The identification of causes of genetic diseases has been carried out by several approaches with increasing complexity. Innovation of genetic methodologies leads to the production of large amounts of data that needs the support of statistical and computational methods to be correctly processed. The aim of the paper is to provide an overview of statistical and computational methods paying attention to methods for the sequence analysis and complex diseases.
Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos
The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.
The normal development and function of tissues are under the regulation of programmed expression of genes involved in the proliferation and differentiation. Tumor development can be identified as the abnormal or deregulated expression of such genes. Two distinct classes of genes have been implicated in cancer development; oncogenes and tumor-suppressor genes. Those genes are potential target for radiation carcinogenesis. However, contemporal view of mutations of oncogenes and tumor-suppressor genes in radiogenic and non-radiogenic human cancers do not match to the spectrum of radiation-induced mutation in the selected genes, and raise the question whether radiations are primarily responsible for the initiation of carcinogenesis by mutation of those genes as primary target. There is now a growing evidence for the radiation to stimulate cell growth, which is followed by suppression. Such stimulatory effects of radiation may evoke the growth-promoting and -suppressing genes, or oncogenes and tumor-suppressor genes. This may lead to a testable proposition that constitutively present gain-of-function mutations in oncogenes and/or loss-of-function mutations in tumor-suppressor genes, accumulated spontaneously or environmentally, may play a significant role in the radiation carcinogenesis. (author)
Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiological diagnosis of pancreatic cancer; Biopsy and cytology in the diagnosis of pancreatic cancer; Pathology and morphology of pancreatic cancer; Staging and prognosis of pancreatic cancer; Biological and immunological markers in the diagnosis of pancreatic cancer; Surgical treatment of pancreatic cancer; Drug therapy of pancreatic cancer; Radiation therapy of pancreatic cancer; Selected studies on the epidemiology of pancreatic cancer; Clinical correlates and syndromes associated with pancreatic neoplasia
Ogilvie, Caroline Mackie; Braude, Peter R; Scriven, Paul N
Since the early 1990s, preimplantation genetic diagnosis (PGD) has been expanding in scope and applications. Selection of female embryos to avoid X-linked disease was carried out first by polymerase chain reaction, then by fluorescence in situ hybridization (FISH), and an ever-increasing number of tests for monogenic diseases have been developed. Couples with chromosome rearrangements such as Robertsonian and reciprocal translocations form a large referral group for most PGD centers and present a special challenge, due to the large number of genetically unbalanced embryos generated by meiotic segregation. Early protocols used blastomeres biopsied from cleavage-stage embryos; testing of first and second polar bodies is now a routine alternative, and blastocyst biopsy can also be used. More recently, the technology has been harnessed to provide PGD-AS, or aneuploidy screening. FISH probes specific for chromosomes commonly found to be aneuploid in early pregnancy loss are used to test blastomeres for aneuploidy, with the aim of replacing euploid embryos and increasing pregnancy rates in groups of women who have poor IVF success rates. More recent application of PGD to areas such as HLA typing and social sex selection have stoked public controversy and concern, while provoking interesting ethical debates and keeping PGD firmly in the public eye. PMID:15749997
Marinho, C D; Martins, F J O; Amaral Júnior, A T; Gonçalves, L S A; dos Santos, O J A P; Alves, D P; Brasileiro, B P; Peternelli, L A
In Brazil, the first genetically modified (GM) crop was released in 1998, and it is estimated that 84, 78, and 50% of crop areas containing soybean, corn, and cotton, respectively, were transgenic in 2012. This intense and rapid adoption rate confirms that the choice to use technology has been the main factor in developing national agriculture. Thus, this review focuses on understanding these dynamics in the context of farmers, trade relations, and legislation. To accomplish this goal, a survey was conducted using the database of the National Cultivar Registry and the National Service for Plant Variety Protection of the Ministry of Agriculture, Livestock and Supply [Ministério da Agricultura, Pecuária e Abastecimento (MAPA)] between 1998 and October 13, 2013. To date, 36 events have been released: five for soybeans, 18 for corn, 12 for cotton, and one for beans. From these events, 1395 cultivars have been developed and registered: 582 for soybean, 783 for corn and 30 for cotton. Monsanto owns 73.05% of the technologies used to develop these cultivars, while the Dow AgroScience - DuPont partnership and Syngenta have 16.34 and 4.37% ownership, respectively. Thus, the provision of transgenic seeds by these companies is an oligopoly supported by legislation. Moreover, there has been a rapid replacement of conventional crops by GM crops, whose technologies belong almost exclusively to four multinational companies, with the major ownership by Monsanto. These results reflect a warning to the government of the increased dependence on multinational corporations for key agricultural commodities. PMID:25061747
... this page: //medlineplus.gov/ency/patientinstructions/000842.htm Genetic testing and your cancer risk To use the sharing ... with one or more of the above About Genetic Testing You may first have a an assessment to ...
King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.
This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.
In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer
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Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk
Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)
Full Text Available ... Caregivers Questions to Ask about Advanced Cancer Research Managing Cancer Care Finding Health Care Services Advance Directives Using Trusted Resources What Is Cancer Cancer Statistics Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening ...
... the body. Cancer can spread through tissue , the lymph system , and the blood : Tissue. The cancer spreads from where it began by growing into nearby areas. Lymph system. The cancer spreads from where it began by ...
Das, Palashpriya; Mukherjee, Soumen; Sen, Ramkrishna
Microbial biosurfactants are surface active metabolites synthesized by microbes growing on a variety of substrates. In spite of having great potential for commercial, therapeutic and environmental applications, industrial level production has not been realized for their low yields and productivities. One vital factor determining their biosynthesis is the genetic makeup of the producer organisms. Studies on molecular genetics and biochemistry of the synthesis of several biosurfactants have revealed the operons, the enzymes and the metabolic pathways required for their extracellular production. Surfactin, a cyclic lipopeptide biosurfactant is a potent antimicrobial agent and is produced as a result of non-ribosomal biosynthesis catalyzed by a large multienzyme peptide synthetase complex called the surfactin synthetase. Pathways for the synthesis of other lipopeptides such as iturin, lichenysin and arthrofactin are also mediated by similar enzyme complexes. These non-ribosomal peptide synthetases (NRPSs) responsible for lipopeptide biosynthesis display a high degree of structural similarity among themselves even from distant microbial species. Plasmid-encoded- rhlA, B, R and I genes of rhl quorum sensing system are required for production of glycolipid biosurfactants by Pseudomonas species. Molecular genetics of biosynthesis of alasan and emulsan by Acinetobacter species and of the fungal biosurfactants such as mannosylerythritol lipids (MEL) and hydrophobins have been deciphered. However, limited genetic information is available about biosynthesis of other biosurfactants such as viscosin, amphisin and putisolvin produced by some strains of Pseudomonas species. Understanding of the genetic regulatory mechanisms would help to develop metabolically engineered hyper-producing strains with better product characteristics and acquired capability of utilizing cheap agro-industrial wastes as substrates. This article thus provides an overview of the role and importance of
Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Lambrechts, Diether; Leunen, Karin; Amant, Frédéric; Vergote, Ignace
Nonepithelial ovarian cancers (OCs), including sex cord-stromal tumors (SCSTs) and germ cell tumors (GCTs), are an uncommon subset of OC, together accounting for 10% of all OCs. The etiology of these tumors remains largely unresolved. It is well established that tumorigenesis is the result of multiple genetic alterations driving a normal cell toward a malignant state. Much effort has been made into researching the molecular mechanisms underlying epithelial OC, but far less is known about the genetic changes in SCSTs and GCTs. Recently, a single point missense mutation (C134W) was found in the FOXL2 gene in approximately 95% of adult-type granulosa cell tumors, suggesting a key role for FOXL2 in these tumors. By contrast, the FOXL2 mutation was not found in the juvenile type. DICER1 somatic missense mutations were found in approximately 60% of Sertoli-Leydig tumors. Ovarian GCTs share many morphological features and a similar pattern of chromosomal alterations with testicular GCTs. In the latter, recent genome-wide association studies have identified seven susceptibility loci near KITLG, SPRY4, UKC2, BAK1, DMRT1, TERT and ATF7IP. All of the susceptibility loci detected thus far are all involved in primordial germ cell function or sex determination. TGF-β/BMP and Wnt/β-catenin signaling was absent in dysgerminomas, but present in yolk sac tumors, suggesting intertumoral heterogeneity. In this article, the authors aim to provide an overview of the current knowledge on the possible molecular changes in SCSTs and GCTs of the ovary. PMID:23875665
Fussi, Barbara; Westergren, Marjana; Aravanopoulos, Filippos; Baier, Roland; Kavaliauskas, Darius; Finzgar, Domen; Alizoti, Paraskevi; Bozic, Gregor; Avramidou, Evangelia; Konnert, Monika; Kraigher, Hojka
Safeguarding sustainability of forest ecosystems with their habitat variability and all their functions is of highest priority. Therefore, the long-term adaptability of forest ecosystems to a changing environment must be secured, e.g., through sustainable forest management. High adaptability is based on biological variation starting at the genetic level. Thus, the ultimate goal of the Convention on Biological Diversity (CBD) to halt the ongoing erosion of biological variation is of utmost importance for forest ecosystem functioning and sustainability. Monitoring of biological diversity over time is needed to detect changes that threaten these biological resources. Genetic variation, as an integral part of biological diversity, needs special attention, and its monitoring can ensure its effective conservation. We compare forest genetic monitoring to other biodiversity monitoring concepts. Forest genetic monitoring (FGM) enables early detection of potentially harmful changes of forest adaptability before these appear at higher biodiversity levels (e.g., species or ecosystem diversity) and can improve the sustainability of applied forest management practices and direct further research. Theoretical genetic monitoring concepts developed up to now need to be evaluated before being implemented on a national and international scale. This article provides an overview of FGM concepts and definitions, discusses their advantages and disadvantages, and provides a flow chart of the steps needed for the optimization and implementation of FGM. FGM is an important module of biodiversity monitoring, and we define an effective FGM scheme as consisting of an assessment of a forest population's capacity to survive, reproduce, and persist under rapid environmental changes on a long-term scale. PMID:27473107
Park, Jong-Min; Lee, Ho-Jae; Yoo, Jun Hwan; Ko, Weon Jin; Cho, Joo Young; Hahm, Ki Baik
"War on cancer" was declared through the National Cancer Act by President Richard Nixon in 1971, but cancer statistics from the American Cancer Society and other sources indicated the failure of this war, suggesting instead focus on the message that a "prevention strategy" might be much more effective than cancer treatment. While cancer statistics notoriously showed sharp increases in incidence as well as in mortality concurrent with economic growth in Asia, fortunately Asian countries benefit from plentiful resources of natural compounds, which can prevent cancer. Just like cancer chemotherapeutics targeted to kill cancer cells in Western countries, natural agents activating molecular mechanisms for cancer prevention, reversion of premalignant tumors, and even ablation of cancer stem cells, are very abundant in Asia. Currently, these natural agents are under very active investigations targeting the hallmarks of cancer prevention, including selective induction of apoptosis in cancer cells, suppression of growth factors or their signaling, suppression of cell proliferation and of cancer-promoting angiogenesis, induction of mesenchymal-epithelial transition, and disruption of the tumor microenvironment, developing promising cancer preventive agents. However, Asia is the most populous continent in the world and some Asian countries do not have the resources to implement cancer screening programs for early detection or treatment. In addition, despite the excellent cancer preventive screening strategies in some Asian countries, well-designed clinical trials for cancer prevention are somewhat delayed compared to Western countries. In this review article, several phytochemicals/phytoceuticals produced and studied in different Asian countries will be introduced, including Korean red ginseng (pride of Korea), curcumin (Indian spice for life), black or green tea (popular in Japan/Sri Lanka), genistein from tofu (famous Chinese food), diallylsulfide or S-allylcysteine (garlic
E. Smid-Koopman (Ellen)
textabstractThe first observations indicative of a role of genetic factors in carcinogenesis were made as early as 1912, when Rous demonstrated that a filterable agent (i.e. virus) could induce cancer in chicken (Rous 1965). In 1914, Boveri postulated a "genetic" theory on carcinogenesis by hypothes
Hormones are central in the carcinogenic process in the breast and in the uterine epithelium. Individual genetically determined variation in the response to hormonal influence may alter susceptibility to breast and endometrial cancers. Many small studies of this hypothesis have generated inconclusive results. Since the effect of any genetic variant is expected to be modest, large studies are needed to draw reliable conclusions. Also, there may be interaction between genetic ...
Wang, Ena; Uccellini, Lorenzo; Marincola, Francesco M.
A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness.
... that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, ... that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one ...
Klein, Alison P
Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited g...
Full Text Available Abstract Background A substantial minority of individuals who initially apply for genetic counselling for breast/ovarian cancer withdraw at an early stage from the counselling process. This study investigated the self-reported reasons for early withdrawal and the factors associated significantly with such withdrawal. Methods Self-report questionnaires were mailed to 83 women who had applied for genetic counselling for breast/ovarian cancer but who subsequently withdrew from the counselling process (the "withdrawers". A comparison group of 105 women who had completed the genetic counselling (the "attendees" received a similar questionnaire. The questionnaire assessed sociodemographic characteristics, reasons for applying for genetic counselling, general distress (MHI-5, cancer-specific distress (IES, and cancer worries. For those women who discontinued the counselling, reasons for withdrawal were also assessed. Results The primary reasons given for withdrawing from counselling were difficulties in anticipating the consequences of genetic counselling (28%, and worries about being unable to adequately cope with an unfavourable test result (20%. Compared to the attendees, the withdrawers were significantly younger, more frequently asymptomatic, more often the first and only member of the family to apply for counselling, and less worried about cancer. Current levels of cancer-specific distress and general distress were comparable between the two groups. Conclusion Younger women, those without a history of cancer, and those who are first in their family to apply are more likely to withdraw prematurely from genetic counselling for breast/ovarian cancer. These withdrawers have no elevated levels of distress. However, a substantial percentage of individuals discontinue counselling due to concerns about their (inability to cope with a possible unfavourable test outcome. This suggests that greater attention should be paid to ways of coping with test
Steel, B J
Skin cancer is common and an increasing problem in the UK. It frequently occurs on the head and neck skin. A significant proportion of the adult population in the UK visits the dentist each year, thus making dental practitioners ideally placed to identify suspicious lesions, which could be skin cancer, as part of their routine extra-oral examination. These patients can then be referred on to hospital or their GP for further management. The dentist can also give advice on risk factors and self-monitoring to patients. This paper aims to describe the risk factors, pathology, presentation and treatments for the three most common forms of skin cancer - basal and squamous cell carcinomas, and malignant melanoma, to give the dental practitioner the knowledge and confidence to examine for and identify these skin cancers. PMID:24852988
... exposure, high levels of estrogen, and a family history of breast cancer can increase a man’s risk ... also show the dimpled appearance called peau d’orange (like the skin of an orange). There may ...
... not feel OK talking about it. Even just reading about sex here may seem a little strange ... ACS Sites Bookstore ACS CAN Shop Cancer Atlas Global Health Finish the Fight Press Room Mobile Site ...
Full Text Available Abstract Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1 mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC. E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.
Full Text Available Andrea J O’Hara, Daphne W Bell National Human Genome Research Institute, Cancer Genetics Branch, National Institutes of Health, Bethesda, MD, USAAbstract: Most sporadic endometrial cancers (ECs can be histologically classified as endometrioid, serous, or clear cell. Each histotype has a distinct natural history, clinical behavior, and genetic etiology. Endometrioid ECs have an overall favorable prognosis. They are typified by high frequency genomic alterations affecting PIK3CA, PIK3R1, PTEN, KRAS, FGFR2, ARID1A (BAF250a, and CTNNB1 (β-catenin, as well as epigenetic silencing of MLH1 resulting in microsatellite instability. Serous and clear cell ECs are clinically aggressive tumors that are rare at presentation but account for a disproportionate fraction of all endometrial cancer deaths. Serous ECs tend to be aneuploid and are typified by frequent genomic alterations affecting TP53 (p53, PPP2R1A, HER-2/ERBB2, PIK3CA, and PTEN; additionally, they display dysregulation of E-cadherin, p16, cyclin E, and BAF250a. The genetic etiology of clear cell ECs resembles that of serous ECs, but it remains relatively poorly defined. A detailed discussion of the characteristic patterns of genomic alterations that distinguish the three major histotypes of endometrial cancer is reviewed herein.Keywords: endometrial, cancer, genomics, genetics, sporadic
The main purpose of this thesis was to identify genetic risk factors using both hypothesis-based and hypothesis-free approaches. In an attempt to identify common disease susceptibility alleles for breast cancer, we started off with a hypothesis-free approach, and performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. As GWAS has been said to underperform for stu...
Each year, tens of thousands of persons are diagnosed with cancer, are treated, and become survivors while still in their reproductive years. Their concerns about possible germ-cell damage as a result of life-saving radiation, chemotherapy, or both are plausible, based on evidence from animal models and from somatic cell mutations in human beings. A 40-year follow-up of survivors of the atomic bomb blasts in Japan showed no detectable genetic damage and suggested that the human gonad is more resistant to radiogenic mutation than the laboratory mouse. The pooled results of studying 12 series of offspring of cancer patients showed a 4% rate of major birth defects (similar to that of the general population) and an excess of fetal loss and low birth weight in offspring of women who received abdominal radiotherapy. According to preliminary evaluation of a new National Cancer Institute collaboration with five cancer registries, offspring of survivors of childhood cancers had no more birth defects than expected and, beyond an increase in probably familial cancers in children younger than 5, no overall increase in childhood cancer. Ideally, genetic and reproductive counseling should take place as soon as cancer is diagnosed (before therapy starts) and again when pregnancy is contemplated. 28 references
... ND, Rubenstein JN, Eggener SE, Kozlowski JM. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol. 2003 Apr;169(4):1219-28. ...
Tong, Shuping; Revill, Peter
Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into ten genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing hepatitis B e antigen (HBeAg) expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance. PMID:27084035
Zamboni Giuseppe; Beghelli Stefania; Moore Patrick S; Scarpa Aldo
Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteratio...
Galli, Maria Cristina
This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described. PMID:27033211
Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation
Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP
Yin, Linda X; Ha, Patrick K
Salivary gland cancers are an incredibly heterogeneous group of tumors that include 24 histologically distinct tumor types. The use of new genetic methods has paved the way for promising advancements in our understanding of the molecular biology underlying each type of tumor. The objective of this review was to highlight common oncogenes, tumor suppressor genes, and cytogenetic and epigenetic changes associated with the most common tumor types: mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, mammary analogue secretory carcinoma, hyalinizing clear cell carcinoma, carcinoma ex pleomorphic adenoma, and acinic cell carcinoma. Recent insights into the pathogenesis of each cancer subtype have helped better define and classify these tumors. Further research in salivary gland cancers should focus on determining the key genes involved in the tumorigenesis of each distinct malignancy and identifying individualized chemotherapies directed at these targets. Cancer 2016;122:1822-31. © 2016 American Cancer Society. PMID:26928905
... on PubMed (1 link) PubMed OMIM (1 link) LUNG CANCER Sources for This Page Berger AH, Imielinski M, Duke F, Wala J, Kaplan N, Shi GX, Andres DA, Meyerson M. Oncogenic RIT1 mutations in lung adenocarcinoma. Oncogene. 2014 Aug 28;33(35):4418- ...
Full Text Available Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.
Expert-reviewed information summary about the genetics of prostate cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for prostate cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary prostate cancer syndrome are also discussed.
Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.
ZHAO Qing-hua; ZHOU Hong-lin
Defects of mismatch repair (MMR) genes also have beenidentified in many kinds of tumors. Loss of MMR functionhas been linked to genetic instability especially microsatelliteinstability that results in high mutation rate. In this review, wediscussed the microsatellite instability observed in thegynecological tumors. We also discussed defects in the DNAmismatch repair in these tumors and their correlation to themicrosatellite instability, as well as the gene mutations due tothe microsatellite instability in these tumors. From thesediscussion, we tried to understand the mechanism ofcarcinogenesis in gynecological tumors from the aspect ofgenetic instability due to mismatch repair defects.
Full Text Available Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Cancer Prevention Overview–for health professionals Research ...
Hollis, Robert L; Gourley, Charlie
Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.
The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention
between patients and their first-degree relatives in regards to cancer laterality and possibly age at initial diagnosis of cancer may suggest an underlying inherited genetic predisposition
This overview on defining risk of respiratory cancer from airborne pollutants summarizes broad issues related to a number of the environmental agents that are discussed in the articles that follow. Lung cancer kills more than 100,000 people annually and is the major form of cancer in both sexes in middle age. Cigarette smoking is the major cause of respiratory cancer and must be taken into account in any study of the effect of an environmental agent on the risk of respiratory cancer, particularly at relatively low levels of excess risk. The agents considered in this series all have the potential for widespread community exposures, either because there is widespread long-term exposure (passive smoking), the agents are direct byproducts of energy consumption (organic particles), have ubiquitous production and use patterns (formaldehyde and fibers), or occur widely in natural settings (radon). Several issues--measurement of exposure, latency, confounding factors and bias, extrapolation from animals to humans, population at risk, and attributable risk--must be considered for each agent. A further issue related to exposure estimates is the relationship of exposure to actual dose. Understanding exposure some 25 to 40 years in the past is important because of the prolonged latency period in the development of respiratory cancers. To the degree that these agents act synergistically with smoking, the reduction of smoking or of exposure to these agents may have greater public health consequences than would be anticipated from the directly measured attributable risk of each of these agents separately
The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)
Breast cancer is overall the most common cancer in women worldwide and endometrial cancer is the most common gynaecological cancer in the industrialized world. History of a first-degree relative with breast or endometrial cancer has been related to a twofold increase in risk of the respective diseases. Whilst genetic risk factors for endometrial cancer in general or for breast cancer in women not carrying any high-penetrance mutations are largely unknown, a polygenic model h...
Expert-reviewed information summary about the genetics of skin cancer — basal cell carcinoma, squamous cell carcinoma, and melanoma — including information about specific gene mutations and related cancer syndromes. The summary also contains information about interventions that may influence the risk of developing skin cancer in individuals who may be genetically susceptible to these syndromes.
Eijzenga, W.; Bleiker, E M A; Hahn, D E E; Kolk, van der, J.; Sidharta, G. N.; Aaronson, N K
Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to identify possible demographic and clinical variables associated significantly with them. Consenting individuals scheduled to undergo cancer genetic counseling completed the Psychosocial Aspects of H...
Full Text Available Defects in structures or functions of mitochondria, mainly involving the oxidative phosphorylation, mitochondrial biogenesis and other metabolic pathways have been shown to be associated with a wide spectrum of clinical phenotypes. The ubiquitous nature of mitochondria and their unique genetic features contribute to the clinical, biochemical and genetic heterogenecity of mitochondrial diseases. This article focuses on the recent advances in the field of mitochondrial disorders with respect to the consequences for an advanced clinical and genetic diagnostics. In addition, an overview on recently identified genetic defects and their pathogenic molecular mechanisms are given.
Puppala, Jharna; Siddapuram, Siva Prasad; Akka, Jyothy; Munshi, Anjana
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes. Hence, it has become a global public health issue. Environmental factors have been found to play a major role in the etiology of NAFLD, especially for genetically susceptible populations. Among these, one of the most important factors is junk food, especially the typical "Western-style" diet rich in simple carbohydrates, saturated fat, and highly processed food materials. Genetic predisposition to NAFLD does occur; however, a precise definition of genetic factors responsible for NAFLD is still lacking. Specific variants of different genes have been shown to present a risk for NAFLD. Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual's genotype. PMID:23357341
Jharna Puppala; Siva Prasad Siddapuram; Jyothy Akka; Anjana Munshi
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today.Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes.Hence,it has become a global public health issue.Environmental factors have been found to play a major role in the etiology of NAFLD,especially for genetically susceptible populations.Among these,one of the most important factors is junk food,especially the typical "Western-style" diet rich in simple carbohydrates,saturated fat,and highly processed food materials.Genetic predisposition to NAFLD does occur; however,a precise definition of genetic factors responsible for NAFLD is still lacking.Specific variants of different genes have been shown to present a risk for NAFLD.Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual's genotype.
... html Xalkori Approved For Rare Genetic Form of Lung Cancer ROS-1 positive NSCLC To use the sharing ... Drug Administration to treat advanced non-small cell lung cancer (NSCLC) with tumors that have a rare ROS- ...
Underhill, Meghan L; Jones, Tarsha; Habin, Karleen
Scientific and technologic advances in genomics have revolutionized genetic counseling and testing, targeted therapy, and cancer screening and prevention. Among younger women, African American and Hispanic women have a higher rate of cancers that are associated with hereditary cancer risk, such as triple-negative breast cancer, which is linked to poorer outcomes. Therefore, genetic testing is particularly important in diverse populations. Unfortunately, all races and ethnic groups are not well represented in current genetic testing practices, leading to disparities in cancer prevention and early detection. PMID:27314195
Expert-reviewed information summary about the genetics of kidney cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for kidney cancer and research aimed at prevention of this disease.
Ovesná, Jaroslava; Demnerová, Kateřina; Pouchová, Vladimíra
Genetically modified organisms (GMOs) are those whose genetic material has been altered by the insertion of a new gene or by the deletion of an existing one(s). Modern biotechnology, in particular, the rise of genetic engineering, has supported the development of GMOs suitable for research purposes and practical applications (Gepts, 2002; Novoselova,Meuwissen, & Huirne, 2007; Sakakibara & Saito, 2006). For over 20 years GM bacteria and other GM organisms have been used in laboratories for the study of gene functions (Maliga & Small, 2007; Ratledge & Kristiansen, 2006). Agricultural plants were the first GMOs to be released into the environment and placed on the market. Farmers around the world use GMsoybeans, GMcorn and GM cotton that are herbicide tolerant, or insect resistant, or combine several traits that reduce the costs associated with crop production (Corinne, Fernandez-Cornejo, & Goodhue, 2004).
Roč. 71, - (1998), s. 40. [ FAO /IAEA International Conference on area-wide control of insect pests integrating the sterile insect and related nuclear and other techniques. 28.05.1998-02.06.1998, Penang] Keywords : Cochliomyia hominivorax * Ceratitis capitata Subject RIV: EB - Genetics ; Molecular Biology
Sutphen, Rebecca; Davila, Barbara; Shappell, Heather; Holtje, Tricia; Vadaparampil, Susan; Friedman, Sue; Toscano, Michele; Armstrong, Joanne
One barrier to genetic testing is the lack of access to genetic counselors. We provided cancer genetic counseling via telephone, through a pilot project for employees of a national health insurer, Aetna, Inc. Knowledge transfer, behavioral intentions, and patient satisfaction were assessed by survey after genetic counseling. Aetna sent an individual email to its employees nationwide notifying them of the availability of a new telephone genetic counseling and testing program and providing a li...
Domanska, Katarina; Malander, Susanne; Staaf, Johan; Karlsson, Anna; Borg, Ake; JÃ¶nsson, GÃ¶ran; Nilbert, Mef
Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....
Jacobs, Chris; Pichert, Gabriella
Identification of a potential genetic susceptibility to cancer and confirmation of a pathogenic gene mutation raises a number of challenging issues for the patient with cancer, their relatives and the health professionals caring for them. The specific risks and management issues associated with rare cancer types have been addressed in the earlier chapters. This chapter considers the wider issues involved in genetic counselling and genetic testing for a genetic susceptibility to cancer for patients, families and health professionals. The first part of the chapter will present the issues raised by the current practice in genetic counselling and genetic testing for cancer susceptibility. The second part of the chapter will address some of the issues raised by the advances in genetic testing technology and the future opportunities provided by personalised medicine and targeted cancer therapy. Facilitating these developments requires closer integration of genomics into mainstream cancer care, challenging the existing paradigm of genetic medicine, adding additional layers of complexity to the risk assessment and management of cancer and presenting wider issues for patients, families, health professionals and clinical services. PMID:27075356
Marshall, Jan D; Maffei, Pietro; Collin, Gayle B.; Naggert, Jürgen K.
Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinic...
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for ovarian cancer is based on data from six randomized trials. Moreover, data from one prospective study and three retrospective studies were used. In total, 10 scientific articles are included, involving 1,282 patients. The results were compared with those of a similar overview from 1996 including 15,042 patients. The conclusions reached can be summarized in the following points: There is no scientific documentation supporting adjuvant radiotherapy for early-stage, low-risk patients. No studies have been reported where adjuvant radiotherapy has been compared with no adjuvant therapy in early-stage, high-risk patients. Adjuvant radiotherapy, either whole abdominal irradiation or intraperitoneal P32, has been compared with adjuvant chemotherapy in early-stage, high-risk patients. There is no scientific evidence to show that there is a difference in efficacy. There is some evidence to suggest that adjuvant radiotherapy after radical surgery leads to an increase in disease-free survival rate for patients with advanced-stage ovarian cancer. There is little documentation on long-term side effects (second malignancy) after adjuvant radiotherapy and no conclusions can be drawn
Barrisford, Glen W.; Singer, Eric A; Rosner, Inger L.; Marston Linehan, W.; Gennady Bratslavsky
Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted mole...
This paper summarizes several experiments conducted at Oak Ridge National Laboratory over the last several years. In 1977, approximately 250 western mosquitofish (Gambusia affinis) were transplanted from a non-contaminated pond into a radionuclide-contaminated settling basin. These, two populations, along with an additional contaminated and non-contaminated population, are the focus of these studies. Parameters measured were DNA strand breaks, fecundity, embryonic abnormalities, and RAPD and allozyme genotypes. The results are as follows: (1) the fish from the contaminated sites had more strand breaks than reference fish; (2) the number of strand breaks were negatively correlated with fecundity and positively correlated with abnormalities; (3) the contaminated populations had higher genetic diversity, and displayed a higher frequency of certain RAPD markers (contaminant-indicative markers) as well as nucleoside phosphorylase (NP) heterozygotes; (4) fish which displayed the contaminant-indicative markers or were NP heterozygotes had higher fecundity and fewer strand breaks than other fish when exposed to radiation. These types of studies are significant because they integrate responses from the molecular, organismal and population levels of biological organization. These results are discussed in relation to needs for future study and relevancy of RAPD research, as well as genetic ecotoxicology in general, to environmental monitoring programs
Leuven, Edwin; Plug, Erik; Rønning, Marte
Using Norwegian cancer registry data we study twin and non-twin siblings to decompose variation in cancer at most common sites and cancer mortality into a genetic, shared environment and individual (unshared environmental) component. Regardless the source of sibling variation, our findings indicate that genes dominate over shared environment in explaining relatively more of the variation in cancer at most common cancer sites (but lung and skin cancer) and cancer mortality. The vast majority o...
Marisser H. Álvarez-Guevara
Full Text Available The first transgenic plants were created in Europe about three decades ago. In Nicaragua, however, there is not commercial cultivation of transgenic crops allowed yet, and the only history of transgenic grain imports occurred in 2005, when the introduction of 15 events of GM maize was first authorized. The Law on Prevention of Risks from Living Modified Organisms by Means of Molecular Biotechnology was published in 2010, and more recently, in September 2012, the Law on Conservation and Sustainable Use of Biodiversity came into force. In line with the resulting requirements from these laws, the Ministry of Agriculture and Forestry (MAGFOR currently works in coordination with the Molecular Biology Center at the University of Central America to ensure that grains imported in the country correspond to events legally authorized. This article begins by presenting an overview of transgenic crops (GMO, their history and their implications for the economy and human health. Next, we describe the current status of GMO in Nicaragua. We conclude that MAGFOR has been successful in fulfilling the law in regards to sampling of imports related to the introduction of GMO grains. It is recommended, however, that for better monitoring of compliance with these laws, it will be necessary to establish a systematic monitoring plan nationwide, aimed at the appropriate screening and detection of transgenic material both in crop seeds as well as in imported grains.
Domanska, Katarina; Malander, Susanne; Staaf, Johan;
Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian canc...
Cohen, M Michael
An overview of German, Nazi, and Holocaust medicine brings together a group of subjects discussed separately elsewhere. Topics considered include German medicine before and during the Nazi era, such as advanced concepts in epidemiology, preventive medicine, public health policy, screening programs, occupational health laws, compensation for certain medical conditions, and two remarkable guidelines for informed consent for medical procedures; also considered are the Nuremberg Code; American models for early Nazi programs, including compulsory sterilization, abusive medical experiments on prison inmates, and discrimination against black people; two ironies in US and Nazi laws; social Darwinism and racial hygiene; complicity of Nazi physicians, including the acts of sterilization, human experimentation, and genocide; Nazi persecution of Jewish physicians; eponyms of unethical German physicians with particular emphasis on Reiter, Hallervorden, and Pernkopf; eponyms of famous physicians who were Nazi victims, including Pick and van Creveld; and finally, a recommendation for convening an international committee of physicians and ethicists to deal with five issues: (a) to propose alternative names for eponyms of physicians who exhibited complicity during the Nazi era; (b) to honor the eponyms and stories of physicians who were victims of Nazi atrocities and genocide; (c) to apply vigorous pressure to those German and Austrian Institutes that have not yet undertaken investigations to determine if the bodies of Nazi victims remain in their collections; (d) to recommend holding annual commemorations in medical schools and research institutes worldwide to remember and to reflect on the victims of compromised medical practice, particularly, but not exclusively, during the Nazi era because atrocities and acts of genocide have occurred elsewhere; and (e) to examine the influence of any political ideology that compromises the practice of medicine. PMID:20151431
Sagi, Michal; Uhlmann, Wendy R
Genetic counseling services have existed in Israel since 1964 and are available in almost all the major hospitals. Given the socialized healthcare system and small country size, genetic services are generally accessible and often free. The existence of founder mutations in various communities in Israel makes genetic testing easier to perform. Yet, the ethnic, cultural and religious diversity of the population has major implications on the design of the screening programs and the use of genetic services. The Israeli Association of Genetic Counselors (IAGC) was established in 2008 and had existed informally since 1989. There are two Master level genetic counseling training programs (6 students/class, 2 year program): Hebrew University-Hadassah Medical School (established in 1997) and the Technion (established in 2009). Genetic counselors' clinical training is largely observational and 2 years of supervised counseling sessions post degree are required for board exam eligibility. Genetic counselors are licensed and lead counseling sessions individually, but currently must work under medical geneticist supervision. This is the first article to summarize the history and training of Master level genetic counselors in Israel. Genetic services, coverage and regulations are also described. PMID:23435755
Al-Salameh, Abdallah; Cohen, Régis; Desailloud, Rachel
Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively). Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases) adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating) DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to elucidate the yet unknown mechanisms underlying sporadic bilateral adrenal hyperplasia. PMID:24817817
Full Text Available Abdallah Al-Salameh,1 Régis Cohen,2 Rachel Desailloud3 1Service de Diabétologie, Endocrinologie et Maladies Métaboliques, Centre Hospitalier de Creil, Creil, France; 2Service d'Endocrinologie, Centre Hospitalier de Saint-Denis, Saint-Denis, France; 3Service d'Endocrinologie, Diabétologie et Nutrition, Centre Hospitalier Universitaire d'Amiens, Amiens, France Abstract: Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively. Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to
in patients with chronic irreversible airflow obstruction, especially in those with early onset of disease or positive family history. Testing is also recommended for immediate family members of those with AATD, asthmatics with persistent airflow obstruction, and infants and older subjects with unexplained liver disease. There are over 100 different AAT gene variants; most are rare and only some are associated with clinical disease.Keywords: AAT, AATD, ZZ, early onset emphysema, panacinar emphysema, neonatal jaundice and hepatitis, childhood liver disease, genetics of alpha1-antitrypsin, alpha1-antitrypsin laboratory testing and phenotyping
Burrell, Rebecca A; McGranahan, Nicholas; Bartek, Jiri; Swanton, Charles
Recent studies have revealed extensive genetic diversity both between and within tumours. This heterogeneity affects key cancer pathways, driving phenotypic variation, and poses a significant challenge to personalized cancer medicine. A major cause of genetic heterogeneity in cancer is genomic instability. This instability leads to an increased mutation rate and can shape the evolution of the cancer genome through a plethora of mechanisms. By understanding these mechanisms we can gain insight into the common pathways of tumour evolution that could support the development of future therapeutic strategies. PMID:24048066
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41,204 patients. The results were compared with those of a similar overview from 1996 including 285,982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival
Eijzenga, W; Bleiker, E M A; Hahn, D E E; Van der Kolk, L E; Sidharta, G N; Aaronson, N K
Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to identify possible demographic and clinical variables associated significantly with them. Consenting individuals scheduled to undergo cancer genetic counseling completed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) prior to or immediately following their counseling session. More than half of the 137 participants reported problems on three or more domains of the PAHC, most often in the domains 'living with cancer' (84%), 'family issues' (46%), 'hereditary predisposition' (45%), and 'child-related issues' (42%). Correlations between the PAHC, the HADS and the DT were low. Previous contact with a psychosocial worker, and having a personal history of cancer were associated significantly with HADS scores, but explained little variance (9%). No background variables were associated significantly with the DT. Previous contact with a psychosocial worker, and having children were significantly associated with several PAHC domains, again explaining only a small percentage of the variance (2-14%). The majority of counselees experience specific cancer genetic counseling-related psychosocial problems. Only a few background variables are associated significantly with distress or psychosocial problems. Thus we recommend using the PAHC or a similar problem-oriented questionnaire routinely in cancer genetic counseling to identify individuals with such problems. PMID:25968807
... Central Sudarshan S, Pinto PA, Neckers L, Linehan WM. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer-- ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...
Bonadies, Danielle C; Brierley, Karina L; Barnett, Rachel E; Baxter, Melanie D; Donenberg, Talia; Ducaine, Whitney L; Ernst, Michelle E; Ernstx, Michelle E; Homer, Jeanne; Judkins, Megan; Lovick, Niki M; Powers, Jacquelyn M; Stanislaw, Christine; Stark, Elizabeth; Stenner, Rio C; Matloff, Ellen T
After repeated media attention in 2013 due to the Angelina Jolie disclosure and the Supreme Court decision to ban gene patents, the demand for cancer genetic counseling and testing services has never been greater. Debate has arisen regarding who should provide such services and the quality of genetics services being offered. In this ongoing case series, we document 35 new cases from 7 states (California, Connecticut, Florida, Georgia, Missouri, Pennsylvania, and Utah) and the District of Columbia of adverse outcomes in cancer genetic testing when performed without the involvement of a certified genetic counselor. We identified 3 major themes of errors: wrong genetic tests ordered, genetic test results misinterpreted, and inadequate genetic counseling. Patient morbidity and mortality were an issue in several of these cases. The complexity of cancer genetic testing and counseling has grown exponentially with the advent of multigene panels that include rare genes and the potential for more variants of uncertain significance. We conclude that genetic counseling and testing should be offered by certified genetics providers to minimize the risks, maximize the benefits, and utilize health care dollars most efficiently. PMID:25098283
Bao, Bin; Ahmad, Aamir; Azmi, Asfar S; Ali, Shadan; Sarkar, Fazlul H
The identification of small subpopulations of cancer stem cells (CSCs) from blood mononuclear cells in human acute myeloid leukemia (AML) in 1997 was a landmark observation that recognized the potential role of CSCs in tumor aggressiveness. Two critical properties contribute to the functional role of CSCs in the establishment and recurrence of cancerous tumors: their capacity for self-renewal and their potential to differentiate into unlimited heterogeneous populations of cancer cells. These findings suggest that CSCs may represent novel therapeutic targets for the treatment and/or prevention of tumor progression, since they appear to be involved in cell migration, invasion, metastasis, and treatment resistance-all of which lead to poor clinical outcomes. The identification of CSC-specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs provide a novel opportunity for cancer research. This overview describes the potential implications of several common CSC markers in the identification of CSC subpopulations that are restricted to common malignant diseases, e.g., leukemia, and breast, prostate, pancreatic, and lung cancers. The role of microRNAs (miRNAs) in the regulation of CSC function is also discussed, as are several methods commonly used in CSC research. The potential role of the antidiabetic drug metformin- which has been shown to have effects on CSCs, and is known to function as an antitumor agent-is discussed as an example of this new class of chemotherapeutics. PMID:23744710
Full Text Available Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA mismatch repair (MMR system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.
Data concerning the psychological impact of high risk of cancer are reviewed, including implications of genetic testing, breast screening,and accuracy of women's risk estimates. Work in progress on prophylactic mastectomy and chemoprevention is reviewed. Research on cancer families, and interventions and prevention strategies for high-risk…
... BP. Fanconi anemia and the development of leukemia. Best practice & research. Clinical Haematology 2014; 27(3-4):214- ... 2007; 39(2):165–167. [PubMed Abstract] Related Resources Cancer Genetics Risk ... and Human Services National Institutes of Health National Cancer Institute ...
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Doreen Marie Agnese
Full Text Available As surgeons who care for patients with breast cancer, the possibility of a cancer diagnosis being related to a hereditary predisposition is always a consideration. Not only are we as surgeons always trying to identify these patients and families, but also we are often asked about a potential hereditary component by the patients and their family members. It is therefore critical that we accurately assess patients to determine who may benefit from genetic testing. Importantly, the potential benefit for identifying a hereditary breast cancer extends beyond the patient to other family members and the risk may not be only for the development of breast cancers, but for other cancers as well. As a surgeon with additional training in clinical cancer genetics, I have perhaps a unique perspective on the issue and feel that a review of some of the more practical considerations is important.
Voorwinden, Jan S; Jaspers, Jan P C
The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network. PMID:26475052
Full Text Available Differentiated non-medullary thyroid cancer (NMTC is mostly sporadic, but the recurrence of familial form of the disease has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer. We aimed to study the telomere-telomerase complex in familial NMTC (FNMTC. The genetic analysis included the measurement in the peripheral blood of relative telomere length (RTL, telomerase reverse transcriptase (hTERT gene amplification, hTERT mRNA expression, telomerase protein activity and search of hTERT or TERC (telomerase RNA component gene mutations. We, also, studied telomeric fusions and associations as well as other chromosomal fragility features by conventional and molecular cytogenetic analyses, in phytohemagglutinin stimulated T-lymphocytes from familial patients, unaffected family members, sporadic PTC patients and healthy subjects. We found that, telomere lenght was significantly shorter in the blood of familial patients compared to sporadic PTCs, healthy subjects, nodular goiter and unaffected siblings. hTERT gene amplification was significantly higher in FNMTC patients compared to the other groups and, in particular, it was significantly greater in offspring with respect to parents. hTERT mRNA expression as well as telomerase activity were significantly higher in FNMTC patients compared to sporadic In addition, we demonstrated that familial patients have a significant increase in spontaneous telomeric associations and telomeric fusions compared to healthy subjects and sporadic cases. Q-FISH analysis demonstrated that familial cases display a significant decrease in the telomeric PNA-FISH signal intensity in metaphase chromsome. Our study demonstrates that patients with FNMTC display an imbalance of the telomeretelomerase complex in the peripheral blood.
Full Text Available Robert P Young1,4, Raewyn J Hopkins1, Gregory D Gamble1, Carol Etzel2, Randa El-Zein2, James D Crapo31Department of Medicine and School of Biological Sciences, University of Auckland, Auckland, New Zealand; 2Department of Epidemiology, UT MD Anderson Cancer Center, Houston, TX, USA; 3National Jewish Health, Denver, CO, USA; 4Synergenz Biosciences Ltd, Auckland, New ZealandAbstract: Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90% of cases of chronic obstructive pulmonary disease (COPD and lung cancer. However, genetic factors may explain why 10%–30% of smokers develop these complications. This perspective reviews the evidence suggesting that COPD is closely linked to susceptibility to lung cancer and outlines the potential relevance of this observation. Epidemiological studies show that COPD is the single most important risk factor for lung cancer among smokers and predates lung cancer in up to 80% of cases. Genome-wide association studies of lung cancer, lung function, and COPD have identified a number of overlapping “susceptibility” loci. With stringent phenotyping, it has recently been shown that several of these overlapping loci are independently associated with both COPD and lung cancer. These loci implicate genes underlying pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium, and link COPD with lung cancer at a molecular genetic level. It is currently possible to derive risk models for lung cancer that incorporate lung cancer-specific genetic variants, recently identified “COPD-related” genetic variants, and clinical variables. Early studies suggest that single nucleotide polymorphism-based risk stratification of smokers might help better target novel prevention and early diagnostic strategies in lung cancer.Keywords: lung cancer, chronic obstructive pulmonary disease, association study, single nucleotide polymorphism, risk model
Kikuchi, Akira; Kinshasa, S.
The genetics of development and cancer have converged in the identification of intra- and extra-cellular signaling pathways that are aberrantly regulated in cancer and are also central to embryonic patterning. The Wnt signaling pathway has provided an outstanding example of this. The genes for β-catenin, APC, and Axin in the Wnt signaling pathway are often mutated in human cancers. In all such cases, the common denominator is the accumulation of cytosolic and nuclear β-catenin and the activat...
Lynch, H.T.; Albano, W. A.; Layton, M A; Kimberling, W J; Lynch, J. F.
Hereditary breast cancer shows a distinctive natural history characterised by an earlier age of onset, excess bilaterality, vertical transmission, heterogeneous tumour associations, and improved survival when compared to its sporadic counterpart. To date, very little attention has been given to interrelationships between breast cancer risk factors and genetics. In the general population, early age of first term pregnancy has been generally accepted as protective against breast cancer. In addi...
Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.
Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.
Lynch, Julie; Venne, Vickie; Berse, Brygida
Objectives To describe the currently available genetic tests that identify hereditary risk for breast cancer. Data sources Systematic review of scientific literature, clinical practice guidelines, and data published by test manufacturers. Conclusion Changes in gene patent laws and advances in sequencing technologies have resulted in rapid expansion of genetic testing. While BRCA1/2 are the most recognized genes linked to breast cancer, several laboratories now offer multi-gene panels to detect many risk-related mutations. Implication for Nursing Practice Genetic testing will be increasingly important in the prevention, diagnosis, and treatment of breast cancer. Oncology and advanced practice nurses need to understand risk factors, significance of various genetic tests, and patient counseling. PMID:25951739
Lim, Bora; Cream, Leah V; Harvey, Harold A
Breast cancer is the most commonly diagnosed cancer in women in United States. From data of American Cancer Society from 2007 reported total of 178,480 women diagnosed with breast cancer. The death rate from breast cancer has decreased in North America over time, but still accounts for second highest cancer death, following lung cancer. Breast cancer is staged based on tumor size, nodal involvement, and distant metastasis like any other solid tumors. However clinical staging is not the only important factor in management of breast cancer. Various molecular features divides breast cancer into many subgroups - that act differently, and respond differently from therapy. Thus the focus of breast cancer treatment has evolved focusing on specific targets. The most important biologic markers in subtyping of breast cancer so far are hormone receptor positivity and HER2/neu protein expression. Five molecular subtypes using intrinsic gene set include Basal mRNA, HER2 + mRNA, Luminal AmRNA, Luminal B mRNA, and Normal-like mRNA. In addition, better understanding of genetic target of breast cancer has given us arsenal of personalized, and more effective treatment approach.This review will focus on examples that highlight several mechanism of tumorigenesis, giving us not just understanding of gene pathways and the molecular biology, that could lead us to therapeutic target. Several important molecular targets have been investigated in preclinical and clinical trials, others are yet to be explored. We will also describe genetic mechanisms discovery related to overcoming resistance to current targeted therapies in breast cancer, including hormone receptor expression and HER 2- neu amplification. We will also review other exciting developments in understanding of breast cancer, the tumor microenvironment and cancer stem cells, and targeting agents in that area. PMID:23288634
Lane, Michelle; Ngueng Feze, Ida; Joly, Yann
Genetic discrimination in the context of genetic testing has been identified as a concern for symptomatic and asymptomatic individuals for more than three decades. Genetic counselors are often the health care professionals who discuss risks and benefits of genetic testing with patients, thereby making them most appropriate to address patient concerns about genetics and personal insurance (i.e., life, life as related to mortgage or group insurance, disability, critical illness and travel). A pilot study was conducted to ascertain the current practices of Canadian cancer genetic counselors in regard to their discussions with patients about genetic testing and access to personal insurance. Among the 36 counselors surveyed, 100 % reported discussing the issue of genetic testing and personal insurance with their patients. Several factors influenced the content, depth and length of these discussions including age, cancer status, family members, and patients' current and future insurance needs. Counselors reported discussing with patients the possible impact of genetic test results on access to personal insurance, possible access and use of patient genetic information by insurance companies, and whom patients should contact if they have additional questions. The most commonly reported inquiries from patients included questions about the possible impact of genetic testing on their ability to obtain insurance, and the insurability of family members. While 28 % of counselors reported having been contacted by an insurer requesting access to patient information, only one counselor was aware of or could recall the outcome of such a request. This pilot study revealed that issues concerning genetics and personal insurance are commonly discussed in Canadian cancer genetic counseling sessions. Counselors furthermore expressed a need for additional educational resources on the topic of genetics and personal insurance for themselves and their patients. PMID:25925606
Guo, Qi; Schmidt, Marjanka K; Kraft, Peter;
BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis of.......2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in...... of genotyping suggested that the finding was less robust. CONCLUSIONS: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic...
Pourhoseingholi, Mohamad Amin; Vahedi, Mohsen; Baghestani, Ahmad Reza
The cancers in the digestive system including gastric cancer, colorectal cancer, liver cancer, esophageal cancer and pancreatic cancer are one of the most common cancers in Asia. The burden of GI cancer is increasing in Asia because of aging, growth of the population and the risk factors including smoking, obesity, changing lifestyle and high prevalence of H pylori, HBV and HCV. In most Asian countries, cancer control programs or early detection and treatment services are limited despite this increase. There are many people in the developing countries inside Asia who have no health insurance and many of them are too poor to go for screening tests, early detection or medical treatments. Therefore, it is important for the health organizations and governments in each country to recognize these groups and reduce the incidence and mortality of gastrointestinal cancers, using simple and economic screening test, vaccination and changing risk factors such as smoking, diet and lifestyle by education programs. PMID:25584172
Eyigor, Sibel; Kanyilmaz, Selcen
Breast cancer is the most common type of cancer in women, but fortunately has high survival rates. Many studies have been performed to investigate the effects of exercise in patients diagnosed with breast cancer. There is evidence that exercise after the diagnosis of breast cancer improves mortality, morbidity, health related quality of life, fatigue, physical functioning, muscle strength, and emotional wellbeing. Based on scientific data, breast cancer patients should be recommended to parti...
Schönfeld, I; Kraywinkel, K
Finding reliable data about cancer epidemiology on the World Wide Web is not an easy task. Information is often scattered, and sources are not always clear. This article gives a short overview of the most important websites that provide reliable data for Germany and Europe. Four internet sites are presented: The German Centre for Cancer Registry Data (ZfKD), the Association of Population-Based Cancer Registries in Germany (GEKID), and two different websites created by the International Agency for Research on Cancer (IARC). In combination, they provide comprehensive information about the distribution of cancer in Germany and Europe. PMID:24357168
Full Text Available Genetic influences on cancer development have been extensively investigated during the last decade following publication of human genome sequence. The present review summarizes case-control studies on genetic polymorphisms and cancer risk in Indians. It is observed that the most commonly studied genes in the Indian population included members of phase I and phase II metabolic enzymes. Other than these genes, genetic polymorphisms for cell cycle and apoptosis-related factors, DNA repair enzymes, immune response elements, growth factors, folate metabolizing enzymes, vitamin/hormone receptors, etc., were investigated. Several studies also evidenced a stronger risk for combined genotypes rather than a single polymorphism. Gene-environment interaction was also found to be a determining factor for cancer development in some experiments. Data for single polymorphism and single cancer type, however, was insufficient to validate an association. It appears that much more experiments involving larger sample size, cross-tabulating genetic polymorphisms and environmental factors are required in order to identify genetic markers for different cancers in Indian populations.
... common treatment for all stages of lip and oral cavity cancer. Surgery may include the following: Wide local excision : Removal ... cancer may have spread from the lip and oral cavity. Plastic surgery : An operation that restores or improves the appearance ...
Although cervical cancer gene therapy has a distance to clinical use due to some problems, the combinating of irradiation and gene therapy holds much promise in cancer therapy based on the traditional radiotherapy, chemotherapy and surgery. This review focuses on the group of radiogenic therapy that are either. (authors)
Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N;
this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had......Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...
Iacono, William G; Malone, Stephen M; Vaidyanathan, Uma; Vrieze, Scott I
This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind the steps taken in the molecular genetic study design. The statistical approach included (a) biometric analysis of twin and family data, (b) heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c) genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d) follow-up analyses of candidate SNPs and genes hypothesized to have an association with each endophenotype, (e) rare variant analysis of nonsynonymous SNPs in the exome, and (f) whole genome sequencing association analysis using 27 million genetic variants. These methods were used in the accompanying empirical articles comprising this special issue, Genome-Wide Scans of Genetic Variants for Psychophysiological Endophenotypes. PMID:25387703
Plucker, Jonathan A; Shelton, Amy L
Current technology has dramatically increased the prevalence of studies to establish the genetic correlates of a wide variety of human characteristics, including not only the physical attributes that determine what we look like and the risk of physiological disease but also the psychological and cognitive characteristics that often define who we are as individuals. Perhaps one of the most deeply personal and often controversial characteristics is the concept of general intelligence, known in the psychological literature as "g." As with the genetic study of any complex trait, the first step in studying the genetics of g is to carefully define the characteristic of interest. For g, this entails establishing what intelligence means and providing a clear operational definition for how it will be measured. In this paper, we provide a brief historical and theoretical overview of the construct of general intelligence, describe its relationship to the contemporary measurement of intelligence, and discuss these concepts in light of the challenges associated with defining g as a characteristic in the study of genetics. PMID:26413944
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Barbara A Hocevar
Full Text Available Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00 ± 0.05 versus both healthy unrelated and related controls (0.70 ± 0.06, pA and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.
Agnese, Doreen M.; Pollock, Raphael E
As surgeons who care for patients with breast cancer, the possibility of a cancer diagnosis being related to a hereditary predisposition is always a consideration. Not only are we as surgeons always trying to identify these patients and families but also we are often asked about a potential hereditary component by the patients and their family members. It is therefore critical that we accurately assess patients to determine who may benefit from genetic testing. Importantly, the potential bene...
Holst, Susanna von
Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) ha...
Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.
Davis, Margaret H.
This overview discusses articles published in this special 30th Anniversary of Medicare issue of the Health Care Financing Review. The authors whose work appears in this special commemorative issue all participated in a policy symposium held on May 6, 1996, at the Lyndon B. Johnson Library in Austin, Texas. The symposium, Medicare: Advancing Towards the 21st Century, was held in honor of the 30th anniversary of the implementation of the Medicare program. Co-sponsors of the symposium included ...
Sigurður Ingvarsson 1956
Somatic changes in the genome of breast cancer cells include amplifications, deletions and gene mutations. Several chromosome regions harboring known oncogenes are found amplified in breast tumors. Despite the high number of chromosome regions deleted in breast tumors the functional relationship to known genes at these locations and cancer growth is mainly undiscovered. Mutations in two tumor suppressor genes (TSG) have been described in a subset of breast carcinomas. These TSG are the TP53, ...
Amit Bali; Deepika Bali; Ashutosh Sharma
Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction...
贾卫华; 王继先; 李本孝; 李征
Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ～ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.
贾卫华; 王继先; 李本孝; 李征
Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.
Malik, Bhavna; Feng, Felix Y
Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044
Zain, R. B.
This is an update on cultural and dietary risk factors for oral precancer and cancer. It is an overview on ethnic differences (where possible) and socio-cultural risk factors (tobacco/areca nut/betel quid, alcohol use and dietary factors) in relation to oral precancer and cancer. While studies were from Western countries, India and China, this update also attempts to include and highlight some studies conducted in the Asia-Pacific region.
Full Text Available Nanotechnology provide innovative tools that shed greater light on life cycle of normal cells andthe point at which molecular processes and changes within cells become correlated with development ofcancer. It should be possible to obtain large amount of information from a small source. They aid inanalysis of parameters such as cellular mechanics, morphology and cytoskeleton which has been hard toachieve using conventional technology.Nano devices can detect cancer cells, identify cancer signatures and provide targeted delivery ofanti cancer therapeutics and contrast agents to tumour cells. The obstacle to early detection of cancer liesin the liability of existing tools to detect molecular level changes during early phases in the developmentof cancer. Nano Technology is potential tool that could help detect the molecular changes and assist infocusing on preventive efforts.
Aaltonen, L. A.; Brenner, H.; Buch, S.; Campbell, H.; Carracedo, A.; Carvajal-Carmona, L.; Castells, A.; Castellví-Bel, S.; Cheadle, J. P.; Devilee, P.; Dunlop, M.; Echeverry, M.; Gallinger, S.; Galvan, A.; Hampe, J.; Hemminki, K.; Ho, J. W. C.; Hofstra, R. M. W.; Hudson, T. J.; Kirac, I.; Lerch, M. M.; Li, L.; Lindblom, A.; Lipton, L.; Matsuda, K.; Maughan, T. S.; Moreno, V.; Morreau, H.; Naccarati, Alessio; Nakamura, Y.; Peterlongo, P.; Pharoah, P. D.; Sieber, O.; Radice, P.; Ruiz-Ponte, C.; Schafmayer, C.; Schmidt, C. A.; von Schönfels, W.; Schreiber, S.; Scott, R.; Sham, P.; Souček, P.; Tenesa, A.; Tomplinson, P. M.; Velez, A.; Villanueva, C. M.; Vodička, Pavel; Völzke, H.; van Wezel, T.; Wijnen, J.T.; Zanke, B.
Roč. 27, č. 2 (2012), s. 143-151. ISSN 0267-8357 Institutional research plan: CEZ:AV0Z50390703 Keywords : identification of low-risk variants * disease causing variants * susceptibility alleles Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012
Vig, Hetal S; Wang, Catharine
Practice changes in cancer genetic counseling have occurred to meet the demand for cancer genetic services. As cancer genetics continues to impact not only prevention strategies but also treatment decisions, current cancer genetic counseling models will need to be tailored to accommodate emerging clinical indications. These clinical indications include: surgical prophylactic bilateral mastectomy candidates, PARP-inhibitor candidates, patients with abnormal tumor screening results for Lynch sy...
Albada, A.; Vernooij, M.; Osch, L. van; Pijpe, A.; Dulmen, S. van; Ausems, M.G.E.M.
To optimally inform counselees about their and their relatives' risks, information about lifestyle risk factors, e.g. physical activity and alcohol consumption, might be discussed in breast cancer genetic counselling. This study explored whether lifestyle was discussed, on whose initiative, whether
Roč. 47, č. 5 (2001), s. 153-155. ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cells * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001
Hong, Andrew L; Tseng, Yuen-Yi; Cowley, Glenn S; Jonas, Oliver; Cheah, Jaime H; Kynnap, Bryan D; Doshi, Mihir B; Oh, Coyin; Meyer, Stephanie C; Church, Alanna J; Gill, Shubhroz; Bielski, Craig M; Keskula, Paula; Imamovic, Alma; Howell, Sara; Kryukov, Gregory V; Clemons, Paul A; Tsherniak, Aviad; Vazquez, Francisca; Crompton, Brian D; Shamji, Alykhan F; Rodriguez-Galindo, Carlos; Janeway, Katherine A; Roberts, Charles W M; Stegmaier, Kimberly; van Hummelen, Paul; Cima, Michael J; Langer, Robert S; Garraway, Levi A; Schreiber, Stuart L; Root, David E; Hahn, William C; Boehm, Jesse S
Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models to perform preclinical studies. As a proof-of-concept, we developed a patient-derived cancer cell line, CLF-PED-015-T, from a paediatric patient with a rare undifferentiated sarcoma. Here, we confirm that this cell line recapitulates the histology and harbours the majority of the somatic genetic alterations found in a metastatic lesion isolated at first relapse. We then perform pooled CRISPR-Cas9 and RNAi loss-of-function screens and a small-molecule screen focused on druggable cancer targets. Integrating these three complementary and orthogonal methods, we identify CDK4 and XPO1 as potential therapeutic targets in this cancer, which has no known alterations in these genes. These observations establish an approach that integrates new patient-derived models, functional genomics and chemical screens to facilitate the discovery of targets in rare cancers. PMID:27329820
Douma, Kirsten F. L.; Smets, Ellen M.A.; Allain, Dawn C.
Non-genetic health professionals (NGHPs) have insufficient knowledge of cancer genetics, express educational needs and are unprepared to counsel their patients regarding their genetic test results. So far, it is unclear how NGHPs perceive their own communication skills. This study was undertaken to gain insight in their perceptions, attitudes and knowledge. Two publically accessible databases were used to invite NGHPs providing cancer genetic services to complete a questionnaire. The survey a...
Cragun, Deborah; Malo, Teri L.; Pal, Tuya; Shibata, David; Vadaparampil, Susan T
Aims: Benefits of universal tumor screening for Lynch syndrome (LS), the most common form of hereditary colorectal cancer (CRC), will be realized only if patients are interested in genetic counseling and testing. This study explores interest in genetic testing for hereditary CRC among CRC patients who have never received genetic counseling or testing. Methods Using results from a cross-sectional survey of CRC patients (n=91) at varying categories of risk for hereditary CRC, bivariate and mult...
Expert-reviewed information summary about the genetics of breast and gynecologic cancers, including information about specific genes and family cancer syndromes. The summary also contains information about interventions that may influence the risk of developing breast and gynecologic cancers in individuals who may be genetically susceptible to these diseases. Psychosocial issues associated with genetic testing are also discussed.
Fertility preservation is becoming increasingly important to improve the quality of life in cancer survivors. Despite guidelines suggesting that discussion of fertility preservation should be done prior to starting cancer therapies, there is a lack of implementation in this area. A number of techniques are available for fertility preservation, and they can be used individually or together in the same patient to maximize efficiency. Oocyte and embryo cryopreservation are now established techni...
Full Text Available The Lethal Yellowing (LY disease is one of the main threats to coconut industry in many parts of Africa and the Caribbean. Planting resistant varieties has long been recognized as one of the most promising ways of controlling the disease. Considerable efforts have been devoted throughout the world to screening suitable varieties and have often involved international cooperation. It has proven to be a lengthy and difficult task. We present an overview of these efforts with special mention to Ghana, Jamaica and Mexico. Although no variety so far has been proven fully and permanently resistant, treating resistance level as a threshold trait makes it possible to demonstrate significant differences among varieties, which can be exploited effectively to make genetic improvement a component of an integrated control strategy. Based on past experience, we make a few suggestions to increase the diversity of resistance sources and increase the level and the sustainability of resistance to LY in coconut.
Full Text Available Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.
Aurisicchio, Luigi, E-mail: firstname.lastname@example.org [Takis, via di Castel Romano 100, 00128 Rome (Italy); BIOGEM scarl, via Camporeale, 83031 Ariano Irpino (AV) (Italy); Ciliberto, Gennaro [Takis, via di Castel Romano 100, 00128 Rome (Italy); Dipartimento di Medicina Sperimentale e Clinica, Università degli studi di Catanzaro “Magna Graecia”, 88100 Catanzaro (Italy)
Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.
Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost
Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek
With the advent of genomics-based treatment in recent years, the use of targeted therapies in the treatment of various malignancies has increased exponentially. Though much data is available regarding the efficacy of targeted therapies for common malignancies, genetic cancer syndromes remain a somewhat unexplored topic with comparatively less published literature. This review seeks to characterize targeted therapy options for the following genetic cancer syndromes: Fanconi anemia, inherited medullary thyroid cancer, tuberous sclerosis, and RASopathies. By understanding the pathophysiology of these conditions as well as available molecularly targeted therapies, oncologists, in collaboration with geneticists and genetic counsellors, can begin to develop effective clinical management options and therapy regimens for the patients with these genetic syndromes that they may encounter in their practice. PMID:25725224
Slattery, Martha L.; Lundgreen, Abbie; Stern, Marianna C.; Hines, Lisa; Wolff, Roger K.; Giuliano, Anna R.; Baumgartner, Kathy B.; John, Esther M.
The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity.
Full Text Available Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for oesophageal cancer is based on data from 42 randomized trials and 2 meta-analyses. A total of 44 scientific articles are included, involving 5,772 patients. The conclusions reached can be summarized as follows: There is fairly strong evidence that preoperative radiotherapy does not improve the survival in patients with potentially resectable oesophageal cancer. There is moderate evidence that preoperative chemo-radiotherapy has no beneficial impact on the survival of patients with potentially resectable oesophageal cancer. There is no scientific evidence that postoperative radiotherapy improves survival in patients with resectable oesophageal cancer. The documentation is, however, poor, consisting of only three randomized trials. There is fairly strong evidence that concomitant (but not sequential) chemo-radiotherapy gives significantly better survival rate than radiotherapy alone in inoperable oesophageal cancer. The results of the reported clinical trials are, however, conflicting, and no solid conclusion can be drawn. Hyperfractionated radiotherapy has been compared with conventionally fractionated radiotherapy in two randomized studies with conflicting results and no firm conclusion can be drawn
Wu, Xinyin; Chung, Vincent CH; Hui, Edwin P; Ziea, Eric TC; Ng, Bacon FL; Ho, Robin ST; Tsoi, Kelvin KF; Wong, Samuel YS; Wu, Justin CY
Acupuncture and related therapies such as moxibustion and transcutaneous electrical nerve stimulation are often used to manage cancer-related symptoms, but their effectiveness and safety are controversial. We conducted this overview to summarise the evidence on acupuncture for palliative care of cancer. Our systematic review synthesised the results from clinical trials of patients with any type of cancer. The methodological quality of the 23 systematic reviews in this overview, assessed using the Methodological Quality of Systematic Reviews Instrument, was found to be satisfactory. There is evidence for the therapeutic effects of acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. There is conflicting evidence regarding the treatment of cancer-related pain, hot flashes and hiccups, and improving patients’ quality of life. The available evidence is currently insufficient to support or refute the potential of acupuncture and related therapies in the management of xerostomia, dyspnea and lymphedema and in the improvement of psychological well-being. No serious adverse effects were reported in any study. Because acupuncture appears to be relatively safe, it could be considered as a complementary form of palliative care for cancer, especially for clinical problems for which conventional care options are limited. PMID:26608664
Wu, Xinyin; Chung, Vincent C H; Hui, Edwin P; Ziea, Eric T C; Ng, Bacon F L; Ho, Robin S T; Tsoi, Kelvin K F; Wong, Samuel Y S; Wu, Justin C Y
Acupuncture and related therapies such as moxibustion and transcutaneous electrical nerve stimulation are often used to manage cancer-related symptoms, but their effectiveness and safety are controversial. We conducted this overview to summarise the evidence on acupuncture for palliative care of cancer. Our systematic review synthesised the results from clinical trials of patients with any type of cancer. The methodological quality of the 23 systematic reviews in this overview, assessed using the Methodological Quality of Systematic Reviews Instrument, was found to be satisfactory. There is evidence for the therapeutic effects of acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. There is conflicting evidence regarding the treatment of cancer-related pain, hot flashes and hiccups, and improving patients' quality of life. The available evidence is currently insufficient to support or refute the potential of acupuncture and related therapies in the management of xerostomia, dyspnea and lymphedema and in the improvement of psychological well-being. No serious adverse effects were reported in any study. Because acupuncture appears to be relatively safe, it could be considered as a complementary form of palliative care for cancer, especially for clinical problems for which conventional care options are limited. PMID:26608664
Rangarajan, Bharath; Shet, Tanuja; Wadasadawala, Tabassum; Nair, Nita S; Sairam, R Madhu; Hingmire, Sachin S; Bajpai, Jyoti
The Incidence of breast cancer has been steadily increasing in the last two decades, more so in urban areas of the sub-continent. Cancer ceters across the country have large numbers of patients being treated with multiple publications in this field. Inspite of paucity of prospective data and randomised clinical trials from India, there are large number of retrospective publications on various aspects of the disease including pathology, radiology, surgery, chemotherapy, radiation, palliative care and alternatitive treatment modalities. These published data provide an insight into the trends of breast cancer in the country and this comprehensive data review of Indian data will provide a basis for designing trials relevant to our population and planning health care. PMID:27606288
Dang, Michelle; Fogley, Rachel; Zon, Leonard I
Chemical genetics is the use of small molecules to perturb biological pathways. This technique is a powerful tool for implicating genes and pathways in developmental programs and disease, and simultaneously provides a platform for the discovery of novel therapeutics. The zebrafish is an advantageous model for in vivo high-throughput small molecule screening due to translational appeal, high fecundity, and a unique set of developmental characteristics that support genetic manipulation, chemical treatment, and phenotype detection. Chemical genetic screens in zebrafish can identify hit compounds that target oncogenic processes-including cancer initiation and maintenance, metastasis, and angiogenesis-and may serve as cancer therapies. Notably, by combining drug discovery and animal testing, in vivo screening of small molecules in zebrafish has enabled rapid translation of hit anti-cancer compounds to the clinic, especially through the repurposing of FDA-approved drugs. Future technological advancements in automation and high-powered imaging, as well as the development and characterization of new mutant and transgenic lines, will expand the scope of chemical genetics in zebrafish. PMID:27165351
Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets
Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Blake Gilks, C; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Webb, Penelope M; Chenevix-Trench, Georgia; Risch, Harvey A; MacGregor, Stuart
Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach. PMID:27075448
Zahm, S.H.; Devesa, S.S. [National Cancer Inst., Rockville, MD (United States)
An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms` tumor. There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol. Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time. Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood. For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults. 143 refs., 1 fig., 3 tabs.
The incidence and mortality rates of skin cancer are rising in the United States and in many other countries. Concerns about stratospheric ozone depletion adding to the problem have made many organizations look at public and professional health programs as a possible solution. Early detection can reduce the problem in the short term, because mortality due to melanoma is clearly related to the depth of invasion of the tumor when it is removed. This is the factor which is amenable to change in an education program on early detection. Exposure to sunlight is clearly related to risk of development of skin cancer, including both melanoma and nonmelanoma skin cancers. This is the component of the equation of constitutional predisposition plus exposure to environmental risk factors leading to skin cancer that is amenable to change as a result of educational programs. On the basis of available data, there is a case for further development, provision, and evaluation of public and professional education programs designed to control what is becoming a major public health problem in the community. PMID:7804986
Breast cancer is one of the most common malignancies of women in the reproductive years. In the Western world there is a trend towards delaying pregnancy to later in life, and in combination with an increased incidence of breast cancer an increased number of women are diagnosed with breast cancer before they have completed their reproductive plans. In addition, breast cancer during pregnancy may affect an increased number of women as the childbearing years are delayed. The survival rate after breast cancer has improved during the last decades, and many young breast cancer survivors will consider a pregnancy subsequent to the completion of adjuvant breast cancer therapy. Traditionally, many women are advised against a pregnancy due to a fear of increased risk of recurrence, especially women with estrogen receptor-positive breast cancer. Due to feasibility issues, evidence from large prospective randomized trials is missing regarding the safety of pregnancy after breast cancer. Today guidelines are based on cohort studies and population-based registry evidence with its limitations. Overall, data suggest that pregnancy after breast cancer therapy is safe, and the current evidence is summarized in this overview. PMID:26542739
Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.
Shields, P.G.; Harris, C.C. (Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (USA))
Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments. 96 refs.
Clarice R Weinberg
Full Text Available Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001, especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer.
Prajna Mishra; Bismita Nayak; R. K. Dey
Advanced drug delivery systems using poly(ethylene glycol) (PEG) is an important development in anti-cancer therapy. PEGylation has the ability to enhance the retention time of the therapeutics like proteins, enzymes small molecular drugs, liposomes and nanoparticles by protecting them against various degrading mechanisms active inside a tissue or cell, which consequently improves their therapeutic potential. PEGylation effectively alters the pharmacokinetics (PK) of a variety of drugs and dr...
Burke, Wylie; Culver, Julie; Pinsky, Linda; Hall, Sarah; Reynolds, Susan E; Yasui, Yutaka; Press, Nancy
Family history is increasingly important in primary care as a means to detect candidates for genetic testing or tailored prevention programs. We evaluated primary care physicians’ skills in assessing family history for breast cancer risk, using unannounced standardized patient visits to 86 general internists and family medicine practitioners in King County, WA. Transcripts of clinical encounters were coded to determine ascertainment of family history, risk assessment, and clinical follow-up. ...
McDonald, Jasmine A; Weathers, Benita; Barg, Frances K.; Troxel, Andrea B; Shea, Judy A; Bowen, Deborah; Guerra, Carmen E.; Halbert, Chanita Hughes
Aims: Scientific agencies rely on individuals to donate their DNA to support research on chronic conditions that disproportionately affect African Americans; however, donation is variable in this population. The purpose of this study was to identify sociodemographic characteristics, health care variables, and cultural values having significant independent associations with intentions to donate blood or saliva samples for cancer genetics research among African American adults. Method: Cross-se...
Pechlivanis, S.; Bermejo, J. L.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Hemminki, K.; Vodička, Pavel; Försti, A.
Roč. 160, č. 6 (2009), s. 933-940. ISSN 0804-4643 R&D Projects: GA ČR GA310/07/1430; GA MZd NR8563 Grant ostatní: EU(SE) LSHC-CT-2004-503465 Institutional research plan: CEZ:AV0Z50390512 Keywords : colorectal cancer * diabetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.539, year: 2009
Michael Dean; Hong Lou
Prostate cancer (PCa) is one of the most common malignancies in the world with over 890 000 cases and over 258 000 deaths worldwide each year.Nearly all mortalities from PCa are due to metastatic disease,typically through tumors that evolve to be hormone-refractory or castrate-resistant.Despite intensive epidemiological study,there are few known environmental risk factors,and age and family history are the major determinants.However,there is extreme heterogeneity in PCa incidence worldwide,suggesting that major determining factors have not been described.Genome-wide association studies have been performed and a considerable number of significant,but low-risk loci have been identified.In addition,several groups have analyzed PCa by determination of genomic copy number,fusion gene generation and targeted resequencing of candidate genes,as well as exome and whole genome sequencing.These initial studies have examined both primary and metastatic tumors as well as murine xenografts and identified somatic alterations in TP53 and other potential driver genes,and the disturbance of androgen response and cell cycle pathways.It is hoped that continued characterization of risk factors as well as gene mutation and misregulation in tumors will aid in understanding,diagnosing and better treating PCa.
Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter
The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature. PMID:26259532
Travis, Lois B.; Rabkin, Charles S.; Brown, Linda Morris; Allan, James M.; Alter, Blanche P.; Ambrosone, Christine B.; Begg, Colin B.; Caporaso, Neil; Chanock, Stephen; DeMichele, Angela; Figg, William Douglas; Mary K Gospodarowicz; Hall, Eric J.; Hisada, Michie; Inskip, Peter
KEYWORDS - CLASSIFICATION: adverse effects;Antineoplastic Agents;biomarkers of individual susceptibility: validation;Biotechnology;cancer epidemiology;chemically induced;Carcinogens;Case-Control Studies;Clinical Trials;Cohort Studies;Congresses;drug therapy;epidemiology;etiology;genetics;Genetic Predisposition to Disease;Humans;methods;mortality;Medical Informatics;Multicenter Studies;Neoplasms;Neoplasms,Radiation-Induced;Neoplasms,Second Primary;radiotherapy;Radiotherapy;Registries;Research;...
Full Text Available Abstract Cervical cancer remains one of the greatest killers of women worldwide. It is difficult to foresee a dramatic increase in cure rate even with the most optimal combination of cytotoxic drugs, surgery, and radiation; therefore, testing of molecular targeted therapies against this malignancy is highly desirable. A number of epigenetic alterations occur during all stages of cervical carcinogenesis in both human papillomavirus and host cellular genomes, which include global DNA hypomethylation, hypermetylation of key tumor suppressor genes, and histone modifications. The reversible nature of epigenetic changes constitutes a target for transcriptional therapies, namely DNA methylation and histone deacetylase inhibitors. To date, studies in patients with cervical cancer have demonstrated the feasibility of reactivating the expression of hypermethylated and silenced tumor suppressor genes as well as the hyperacetylating and inhibitory effect upon histone deacetylase activity in tumor tissues after treatment with demethylating and histone deacetylase inhibitors. In addition, detection of epigenetic changes in cytological smears, serum DNA, and peripheral blood are of potential interest for development of novel biomolecular markers for early detection, prediction of response, and prognosis.
Yanju Bao; Xiangying Kong; Liping Yang; Rui Liu; Zhan Shi; Weidong Li; Baojin Hua; Wei Hou
Background and Objective. Now with more and more published systematic reviews of Complementary and Alternative Medicine (CAM) on adult cancer pain, it is necessary to use the methods of overview of systematic review to summarize available evidence, appraise the evidence level, and give suggestions to future research and practice. Methods. A comprehensive search (the Cochrane Library, PubMed, Embase, and ISI Web of Knowledge) was conducted to identify all systematic reviews or meta-analyses of...
Ambrosone, Christine B; Moysich, Kirsten B.; Furberg, Helena; Freudenheim, Jo L.; Bowman, Elise D.; Ahmed, Sabrina; Graham, Saxon; Vena, John E; Shields, Peter G.
Background Findings from previous studies regarding the association between the CYP17 genotype and breast cancer are inconsistent. We investigated the role of the MspAI genetic polymorphism in the 5' region of CYP17 on risk of breast cancer and as a modifier of reproductive risk factors. Methods Questionnaire and genotyping data were obtained from a population-based, case–control study of premenopausal (n = 182) and postmenopausal (n = 214) European-American Caucasian women in western New Yor...
van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Brocker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; Van Gool, A. R.; Klijn, J. G. M.; Tibben, A.
Background: This study explores the effect of age at the time of parental cancer diagnosis or death on psychological distress and cancer risk perception in individuals undergoing genetic testing for a specific cancer susceptibility. Patients and methods: Cancer-related distress, worry and risk perce
Amanda Muglia-Wechsler; Carmen Bragado-Álvarez; María J. Hernández-Lloreda
This article aims at providing a general overview of psychological interventions intended to promote psychological adjustment of children with cancer and their parents. To achieve this goal, we reviewed published articles between 1998-2010, using a combination of the following key words: psychosocial intervention, psychotherapy, trial, treatment, adjustment, wellbeing, adaptation, cancer, childhood cancer, pediatric cancer, anxiety and depression in the electronic databases: Psycinfo, Medline...
Saritha Katta; Inderjeet Kaur; Subhabrata Chakrabarti
Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly. While the prevalence is relatively higher in the Caucasian populations, it has gradually become a major public health issue among the non-Caucasian populations (including Indians) as well due to senescence, rapidly changing demographics and life-style factors. Recent genome-wide association studies (GWAS) on large case–control cohorts have helped in mapping genes in the complement cascade that are involved in the regulation of innate immunity with AMD susceptibility. Genes involved with mitochondrial oxidative stress and extracellular matrix regulation also play a role in AMD pathogenesis. Majority of the associations observed in complement (CFH, CFB, C2 and C3) and other (ARMS2 and HTRA1) genes have been replicated in diverse populations worldwide. Gene–gene (CFH with ARMS2 and HTRA1) interactions and correlations with environmental traits (smoking and body mass index) have been established as significant covariates in AMD pathology. In this review, we have provided an overview on the underlying molecular genetic mechanisms in AMD worldwide and highlight the AMD-associated-candidate genes and their potential role in disease pathogenesis.
Ratner, Elena; Lu, Lingeng; Boeke, Marta; Barnett, Rachel; Nallur, Sunitha; Chin, Lena J; Pelletier, Cory; Blitzblau, Rachel; Tassi, Renata; Paranjape, Trupti; Hui, Pei; Andrew K Godwin; Yu, Herbert; Risch, Harvey; Rutherford, Thomas
Ovarian cancer is the single most deadly form of women’s cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of ovarian cancer and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant,...
Linda S Lindström
Full Text Available BACKGROUND: In lung cancer, a patient's survival is poor with a wide variation in survival within the stage of disease. The aim of this study was to investigate the familial concordance in lung cancer survival by means of analyses of pairs with different degrees of familial relationships. METHODS: Our population-based Swedish family database included three million families and over 58,100 lung cancer patients. We modelled the proband (parent, sibling, spouse survival utilizing a multivariate proportional hazard (Cox model adjusting for possible confounders of survival. Subsequently, the survival in proband's relative (child, sibling, spouse was analysed with a Cox model. FINDINGS: By use of Cox modelling with 5 years follow-up, we noted a decreased hazard ratio for death in children with good parental survival (Hazard Ratio [HR] = 0.71, 95% CI = 0.51 to 0.99, compared to those with poor parental survival. Also for siblings, a very strong protective effect was seen (HR = 0.14, 95% CI = 0.030 to 0.65. Finally, in spouses no correlation in survival was found. INTERPRETATION: Our findings suggest that genetic factors are important in lung cancer survival. In a clinical setting, information on prognosis in a relative may be vital in foreseeing the survival in an individual newly diagnosed with lung cancer. Future molecular studies enhancing the understanding of the underlying mechanisms and pathways are needed.
Full Text Available Background and Objective. Now with more and more published systematic reviews of Complementary and Alternative Medicine (CAM on adult cancer pain, it is necessary to use the methods of overview of systematic review to summarize available evidence, appraise the evidence level, and give suggestions to future research and practice. Methods. A comprehensive search (the Cochrane Library, PubMed, Embase, and ISI Web of Knowledge was conducted to identify all systematic reviews or meta-analyses of CAM on adult cancer pain. And the evidence levels were evaluated using GRADE approach. Results. 27 systematic reviews were included. Based on available evidence, we could find that psychoeducational interventions, music interventions, acupuncture plus drug therapy, Chinese herbal medicine plus cancer therapy, compound kushen injection, reflexology, lycopene, TENS, qigong, cupping, cannabis, Reiki, homeopathy (Traumeel, and creative arts therapies might have beneficial effects on adult cancer pain. No benefits were found for acupuncture (versus drug therapy or shame acupuncture, and the results were inconsistent for massage therapy, transcutaneous electric nerve stimulation (TENS, and Viscum album L plus cancer treatment. However, the evidence levels for these interventions were low or moderate due to high risk of bias and/or small sample size of primary studies. Conclusion. CAM may be beneficial for alleviating cancer pain, but the evidence levels were found to be low or moderate. Future large and rigor randomized controlled studies are needed to confirm the benefits of CAM on adult cancer pain.
Bao, Yanju; Kong, Xiangying; Yang, Liping; Liu, Rui; Shi, Zhan; Li, Weidong; Hua, Baojin; Hou, Wei
Background and Objective. Now with more and more published systematic reviews of Complementary and Alternative Medicine (CAM) on adult cancer pain, it is necessary to use the methods of overview of systematic review to summarize available evidence, appraise the evidence level, and give suggestions to future research and practice. Methods. A comprehensive search (the Cochrane Library, PubMed, Embase, and ISI Web of Knowledge) was conducted to identify all systematic reviews or meta-analyses of CAM on adult cancer pain. And the evidence levels were evaluated using GRADE approach. Results. 27 systematic reviews were included. Based on available evidence, we could find that psychoeducational interventions, music interventions, acupuncture plus drug therapy, Chinese herbal medicine plus cancer therapy, compound kushen injection, reflexology, lycopene, TENS, qigong, cupping, cannabis, Reiki, homeopathy (Traumeel), and creative arts therapies might have beneficial effects on adult cancer pain. No benefits were found for acupuncture (versus drug therapy or shame acupuncture), and the results were inconsistent for massage therapy, transcutaneous electric nerve stimulation (TENS), and Viscum album L plus cancer treatment. However, the evidence levels for these interventions were low or moderate due to high risk of bias and/or small sample size of primary studies. Conclusion. CAM may be beneficial for alleviating cancer pain, but the evidence levels were found to be low or moderate. Future large and rigor randomized controlled studies are needed to confirm the benefits of CAM on adult cancer pain. PMID:24817897
Palmquist, Aunchalee E. L.; Upton, Rachel; Lee, Seungjin; Panter, Abby T.; Hadley, Don W.; Koehly, Laura M.
Objective: To assess beliefs about the role of diet in cancer prevention among individuals considering genetic testing for Lynch Syndrome. Design: Family-centered, cascade recruitment; baseline assessment of a longitudinal study. Setting: Clinical research setting. Participants: Participants were 390 persons, ages 18 and older, including persons…
Buchanan, Adam Hudson; Rahm, Alanna Kulchak; Williams, Janet L.
Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care, and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state o...
Michelle Guy; Helen I.Field; Melissa C.Southey; Gianluca Severi; Jenny L.Donovan; Freddie C.Hamdy; David P.Dearnaley; Kenneth R.Muir; Charmaine Smith; Melisa Bagnato; Audrey T.Ardern-Jones; Zsofia Kote-Jarai; Amanda L.Hall; Lynne T.O'Brien; Beatrice N.Gehr-Swain; Rosemary A.Wilkinson; Angela Cox; Sarah Lewis; Paul M.Brown; Sameer G.Jhavar; Malgorzata Tymrakiewicz; Artitaya Lophatananon; Graham G.Giles; Sarah L.Bryant; The UK Genetic Prostate Cancer Study Collaborators; British Association of Urological Surgeons' Sectio; Alan Horwich; Robert A.Huddart; Vincent S.Khoo; Christopher C.Parker; Christopher J.Woodhouse; Alan Thompson; Tim Christmas; Ali Amin Al Olama; Chris Ogden; Cyril Fisher; Charles Jameson; Colin S.Cooper; Dallas R.English; John L.Hopper; David E.Neal; Douglas E Easton; Rosalind A.Eeles; Sarah K.Jugurnauth; Shani Mulholland; Daniel A.Leongamomlert; Stephen M.Edwards; Jonathan Morrison
There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies.We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified.Three of these loci contain candidate susceptibility genes:MSMB,LMTK2 and KLK2/3.The MSMB and KLK2/3 genes may he useful for PCa screening,and the LMTK2 gene might provide a potential therapeutic target.Together with results from other groups,there are now 23 germline genetic variants which have been reported.These results have the potential to be developed into a genetic test.However,we consider that marketing of tests to the public is premature,as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed.Follow-up validation studies,as well as studies to explore the psychological implications of genetic profile testing,will be vital prior to roll out into healthcare.
Bleiker Eveline MA; Menko Fred H; Kluijt Irma; Taal Babs G; Gerritsma Miranda A; Wever Lidwina DV; Aaronson Neil K
Abstract Background This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling. Methods In this cross-sectional study, individuals who had received genetic counselling for HNPCC dur...
Expert-reviewed information summary in which cancer risk perception, risk communication, and risk counseling are discussed. The summary also contains information about recording and analyzing a family history of cancer and factors to consider when offering genetic testing.
Morgan, Richard A.; Dudley, Mark E.; Wunderlich, John R.; Hughes, Marybeth S.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Topalian, Suzanne L.; Kammula, Udai S.; Restifo, Nicholas P.; Zheng, Zhili; Nahvi, Azam; de Vries, Christiaan R.; Rogers-Freezer, Linda J.; Mavroukakis, Sharon A.; Rosenberg, Steven A.
Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.
Malcolm J. Simons
The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20-21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modem day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome
Full Text Available Despite important advances in microarray-based molecular classification of tumors, its application in clinical settings remains formidable. This is in part due to the limitation of current analysis programs in discovering robust biomarkers and developing classifiers with a practical set of genes. Genetic programming (GP is a type of machine learning technique that uses evolutionary algorithm to simulate natural selection as well as population dynamics, hence leading to simple and comprehensible classifiers. Here we applied GP to cancer expression profiling data to select feature genes and build molecular classifiers by mathematical integration of these genes. Analysis of thousands of GP classifiers generated for a prostate cancer data set revealed repetitive use of a set of highly discriminative feature genes, many of which are known to be disease associated. GP classifiers often comprise five or less genes and successfully predict cancer types and subtypes. More importantly, GP classifiers generated in one study are able to predict samples from an independent study, which may have used different microarray platforms. In addition, GP yielded classification accuracy better than or similar to conventional classification methods. Furthermore, the mathematical expression of GP classifiers provides insights into relationships between classifier genes. Taken together, our results demonstrate that GP may be valuable for generating effective classifiers containing a practical set of genes for diagnostic/ prognostic cancer classification.
Bengel, Jürgen; Barth, Jürgen; Reitz, Frauke
In the past years advances in genetic technologies have led to an increased interest in predictive genetic testing for breast cancer risk. Studies in the US and UK reported an increasing interest among women of the general public in genetic testing for breast cancer risk, although the benefit of such a test is questionable for low risk women. The aim of the present study was to identify factors that predict interest in genetic testing of German women in the general public. Women with neither ...
Ratner, Elena; Lu, Lingeng; Boeke, Marta; Barnett, Rachel; Nallur, Sunitha; Chin, Lena J; Pelletier, Cory; Blitzblau, Rachel; Tassi, Renata; Paranjape, Trupti; Hui, Pei; Godwin, Andrew K; Yu, Herbert; Risch, Harvey; Rutherford, Thomas; Schwartz, Peter; Santin, Alessandro; Matloff, Ellen; Zelterman, Daniel; Slack, Frank J; Weidhaas, Joanne B
Ovarian cancer (OC) is the single most deadly form of women's cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA (miRNA) let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of OC and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant, which disrupts a let-7 miRNA binding site in this oncogene. Specimens obtained were tested for the presence of the KRAS-variant from nonselected OC patients in three independent cohorts, two independent ovarian case-control studies, and OC patients with hereditary breast and ovarian cancer syndrome (HBOC) as well as their family members. Our results indicate that the KRAS-variant is associated with more than 25% of nonselected OC cases. Further, we found that it is a marker for a significant increased risk of developing OC, as confirmed by two independent case-control analyses. Lastly, we determined that the KRAS-variant was present in 61% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Our findings strongly support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing OC, and they suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities. PMID:20647319
Okuyama Kishima, Marina; Brajão de Oliveira, Karen; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Losi Guembarovski, Roberta; Banin Hirata, Bruna Karina; de Almeida, Felipe Campos; Vitiello, Glauco Akelinghton Freire; Trugilo, Kleber Paiva; Guembarovski, Alda Fiorina Maria Losi; Jorge Sobrinho, Walter; Campos, Clodoaldo Zago; Watanabe, Maria Angelica Ehara
CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis. PMID:26576337
Full Text Available Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve. These discoveries will change the way that breast cancer risk is understood in Mexico over the next few decades.La investigación en cáncer de mama ha dado varios resultados importantes incluyendo los genes fuertemente susceptibles, BRCA1 y BRCA2, y más recientemente 19 genes y loci genéticos que confieren un riesgo moderado. El ritmo de los descubrimientos se acelera conforme mejora la tecnología y métodos computacionales.Estosdescubrimientoscambiarán la forma en que la investigación del cáncer es comprendida en México en las próximas décadas.
Full Text Available The prevalence of testicular germ cell tumors (TGCT, a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC into gonocytes, the increase has been attributed to maternal/fetal exposures to environmental factors. We examined the effects of an estrogen (diethylstilbestrol, DES, an antiandrogen (flutamide, or radiation on the incidence of testicular germ cell tumors in genetically predisposed 129.MOLF-L1 (L1 congenic mice by exposing them to these agents on days 10.5 and 11.5 of pregnancy. Neither flutamide nor DES produced noticeable increases in testis cancer incidence at 4 weeks of age. In contrast, two doses of 0.8-Gy radiation increased the incidence of TGCT from 45% to 100% in the offspring. The percentage of mice with bilateral tumors, weights of testes with TGCT, and the percentage of tumors that were clearly teratomas were higher in the irradiated mice than in controls, indicating that irradiation induced more aggressive tumors and/or more foci of initiation sites in each testis. This radiation dose did not disrupt spermatogenesis, which was qualitatively normal in tumor-free testes although they were reduced in size. This is the first proof of induction of testicular cancer by an environmental agent and suggests that the male fetus of women exposed to radiation at about 5-6 weeks of pregnancy might have an increased risk of developing testicular cancer. Furthermore, it provides a novel tool for studying the molecular and cellular events of testicular cancer pathogenesis.
Liebe, Roman; Milkiewicz, Piotr; Krawczyk, Marek; Bonfrate, Leonilde; Portincasa, Piero; Krawczyk, Marcin
Gallbladder cancer (GbCa) is the most frequent malignancy of the biliary tract. It is also the 6th most common gastrointestinal tumor. It is associated with very high lethality, mainly due to the lack of symptoms up to a very late and thus incurable state. As many as 80% of patients are diagnosed at very late stages of disease, which allow only palliative therapy. As a result, most of the patients with GbCa will die within 6 months of the diagnosis, hence the average 5-year survival does not exceed 5%. Currently, surgical resection represents the only curative option in GbCa, but this approach is feasible only at an early stage of the disease. Other oncologic therapies are of limited use. The incidence of GbCa is remarkably increased in certain populations such as Native North Americans, South Indian females and, in Europe, in the Polish population. It is not clear to date if these enhanced risk populations are the result of common environmental exposure or of shared genetic risk factors. In this review we provide an overview of the state-of-art in GbCa research with the focus on the current knowledge concerning genetic and environmental triggers of this tumor. PMID:26405706
Birgisson, Helgi; Paahlman, Lars; Gunnarsson, Ulf [Dept. of Surgery, Univ. Hospital, Univ. of Uppsala, Uppsala (Sweden); Glimelius, Bengt [Dept. of Oncology, Radiology and Clinical Immunology, Univ. Hospital, Univ. of Uppsala, Uppsala (Sweden); Dept. of Oncology and Pathology, Karolinska Inst., Stockholm (Sweden)
Purpose. The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. Methods. Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5x5 Gy radiation therapy with surgery alone. Results. The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. Conclusions. These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.
Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)
Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it`s alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author).
To examine the loci of putative tumor suppressor genes in ovarian cancers, we performed the molecular genetic analysis with fresh human ovarian cancers and observed the following data. Frequent allelic losses were observed on chromosomes 4p(42%), 6p(50%), 7p(43%), 8q(31%), 12p(38%), 12q(33%), 16p(33%), 16q(37%), and 19p(34%) in addition to the previously reported 6q, 11p, and 17p in ovarian caroinomas. we have used an additional probe, TCP10 to narrow down the deleted region on chromosome 6q. TCP10 was reported to be mapped to 6q 25-27. Allelic loss was found to be 40% in epithelial ovarian caroinomas. This finding suggests that chromosome 6q 24-27 is one of putative region haboring the tumor suppressor gene of epithelial ovarian cancer (particularly serous type). To examine the association between FAL(Fractional Allelic Loss) and histopathological features, the FAL value on each phenotypically different tumor was calculated as the ratio of the number of allelic losses versus the number of cases informative in each chromosomal arm. The average FALs for each phenotypically different tumor were: serous cystoadenocarcinomas. FAL=0.31 : mucinous 0.12 : and clear cell carcinoma. FAL=0.20. (Author)
Black Issues in Higher Education, 2005
Black women with a family history of breast cancer are much less likely than Whites to get genetic counseling, in part because of the mistaken notion that the genetic form of the illness is a White woman's disease, researchers say. While breast cancer generally is more common among White women, some data suggest both races have similar rates of…
Plon, S.E.; Eccles, D.M.; Easton, D.; Foulkes, W.D.; Genuardi, M.; Greenblatt, M.S.; Hogervorst, F.B.; Hoogerbrugge, N.; Spurdle, A.B.; Tavtigian, S.V.
Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genet
Naccarati, Alessio; Poláková, Veronika; Pardini, Barbara; Vodičková, Ludmila; Hemminki, K.; Kumar, R.; Vodička, Pavel (ed.)
Roč. 27, č. 2 (2012), s. 211-218. ISSN 0267-8357 R&D Projects: GA ČR GP305/09/P194; GA ČR GAP304/10/1286 Grant ostatní: GA UK(CZ) GA96908/B/2008 Institutional research plan: CEZ:AV0Z50390512 Keywords : TP53 mutations * TP53 polymorphisms * cancer risk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012
, environmental chemical toxins, allopathic drugs, pesticide infected food with heavy metals and some not properly developed metallic preparation of Ayurvedic or other Folk Medicine can be a causative factor, leave aside genetic processes of the Individual for the development of the risk of cancer. If we look in the properties of WS like adaptogen/ anti-stress agent, immunomodulator, antioxidant (reducing free radical damage, anabolic effect, improving resistance of body, reducing fatigue and detoxificant effects, we are inclined to suggests that WS works through all above mechanisms in controlling the dreaded cancer, rather than its effect on stopping the cell division. As during radio and chemotherapy body’s natural normal cells are also killed and low immunity develops, WS helps prevent these adverse effects of both and helps patients better recovery and life styles. However, multicentric long term clinical studies by oncologists, although deviated from their routine, must be carried out on WS to prove our contentions.
Ji, Zhenyu; Mei, Fang C; Lory, Pedro L.; Gilbertson, Scott R.; Chen, Yijun; Cheng, Xiaodong
Pancreatic cancer is one of the deadliest diseases largely due to difficulty in early diagnosis and the lack of effective treatments. KRAS is mutated in more than 90% of pancreatic cancer patients, and oncogenic KRAS contributes to pancreatic cancer tumorigenesis and progression. In this report, using an oncogenic KRASV12-based pancreatic cancer cell model, we developed a chemical genetic screen to identify small chemical inhibitors that selectively target pancreatic cancer cells with gain-of...
Widmer, Colin L; Wolfe, Christopher R; Reyna, Valerie F; Cedillos-Whynott, Elizabeth M; Brust-Renck, Priscila G; Weil, Audrey M
The intelligent tutoring system (ITS) BRCA Gist is a Web-based tutor developed using the Shareable Knowledge Objects (SKO) platform that uses latent semantic analysis to engage women in natural-language dialogues to teach about breast cancer risk. BRCA Gist appears to be the first ITS designed to assist patients' health decision making. Two studies provide fine-grained analyses of the verbal interactions between BRCA Gist and women responding to five questions pertaining to breast cancer and genetic risk. We examined how "gist explanations" generated by participants during natural-language dialogues related to outcomes. Using reliable rubrics, scripts of the participants' verbal interactions with BRCA Gist were rated for content and for the appropriateness of the tutor's responses. Human researchers' scores for the content covered by the participants were strongly correlated with the coverage scores generated by BRCA Gist, indicating that BRCA Gist accurately assesses the extent to which people respond appropriately. In Study 1, participants' performance during the dialogues was consistently associated with learning outcomes about breast cancer risk. Study 2 was a field study with a more diverse population. Participants with an undergraduate degree or less education who were randomly assigned to BRCA Gist scored higher on tests of knowledge than those assigned to the National Cancer Institute website or than a control group. We replicated findings that the more expected content that participants included in their gist explanations, the better they performed on outcome measures. As fuzzy-trace theory suggests, encouraging people to develop and elaborate upon gist explanations appears to improve learning, comprehension, and decision making. PMID:25921818
Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.)
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for cervical cancer is based on data from 1 meta-analysis and 34 randomized trials. In total, 35 scientific articles are included, involving 7,952 patients. The results were compared with those of a similar overview from 1996 including 34,024 patients. The conclusions reached can be summarized in these points: There are limited scientific data supporting that postoperative pelvic radiotherapy improves disease-free survival in early cervical cancer. No firm conclusion can be drawn. There is moderate scientific evidence that external beam radiotherapy combined with brachytherapy gives a similar disease-free and overall survival rate as radical hysterectomy in early cervical cancer. There is strong scientific evidence that concomitant radiochemotherapy improves disease-free and overall survival compared to radiotherapy alone in early cervical cancer. The NCI has recently published an announcement stating that cisplantin-based chemotherapy should be used concomitantly with radiotherapy in cervical cancer. No solid documentation for this statement can be found concerning locally advanced stages (>IIB). There is a strong scientific evidence that cisplatin-based chemotherapy given concomitantly with radiotherapy is superior to concomitant chemotherapy with hydroxyurea. There is no scientific evidence to show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free or overall survival compared to radiotherapy alone in patients with localized cervical cancer. There is moderate scientific evidence that high-dose-rate brachytherapy gives the same local control rate as low-dose-rate brachytherapy but with fewer rectal complications
Dijk, Sandra van
The cumulative lifetime risk of developing breast cancer for a Dutch woman is about 12%. In some families breast cancer seems to occur even more frequently or women fall ill at a relatively young age. Such families may have a genetic susceptibility towards breast cancer. To learn more about the like
Campa, D.; Rizzato, C.; Capurso, G.; Giese, N.; Funel, N.; Greenhalf, W.; Souček, P.; Gazouli, M.; Pezzilli, R.; Pasquali, C.; Talar-Wojnarowska, R.; Cantore, M.; Andriulli, A.; Scarpa, A.; Jamroziak, K.; Delle Fave, G.; Costello, E.; Khaw, K. T.; Heller, A.; Key, T. K.; Theodoropoulos, G.; Malecka-Panas, E.; Mambrini, A.; Bambi, F.; Landi, S.; Pedrazzoli, S.; Bassi, C.; Pacetti, P.; Piepoli, A.; Tavano, F.; di Sebastiano, P.; Vodičková, Ludmila; Basso, D.; Plebani, M.; Fogar, P.; Buechler, M. W.; Bugert, P.; Vodička, Pavel; Boggi, U.; Neoptolemos, J. P.; Werner, J.; Canzian, F.
Roč. 45, č. 2 (2013), s. 95-99. ISSN 1590-8658 Institutional support: RVO:68378041 Keywords : cancer susceptibility * genetic polymorphisms * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.889, year: 2013
Park, Solip; Lehner, Ben
Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another. PMID:26227665
Full Text Available Abstract Background Counselees are more aware of genetics and seek information, reassurance, screening and genetic testing. Risk counseling is a key component of genetic counseling process helping patients to achieve a realistic view for their own personal risk and therefore adapt to the medical, psychological and familial implications of disease and to encourage the patient to make informed choices 12. The aim of this study was to conceptualize risk perception and anxiety about cancer in individuals attending to genetic counseling. Methods The questionnaire study measured risk perception and anxiety about cancer at three time points: before and one week after initial genetic counseling and one year after completed genetic investigations. Eligibility criteria were designed to include only index patients without a previous genetic consultation in the family. A total of 215 individuals were included. Data was collected during three years period. Results Before genetic counseling all of the unaffected participants subjectively estimated their risk as higher than their objective risk. Participants with a similar risk as the population overestimated their risk most. All risk groups estimated the risk for children's/siblings to be lower than their own. The benefits of preventive surveillance program were well understood among unaffected participants. The difference in subjective risk perception before and directly after genetic counseling was statistically significantly lower in all risk groups. Difference in risk perception for children as well as for population was also statistically significant. Experienced anxiety about developing cancer in the unaffected subjects was lower after genetic counseling compared to baseline in all groups. Anxiety about cancer had clear correlation to perceived risk of cancer before and one year after genetic investigations. The affected participants overestimated their children's risk as well as risk for anyone in
Tarleton, Heather P; Chang, Shen-Chih; Park, Sungshim Lani; Cai, Lin; Ding, Baoguo; He, Na; Hussain, Shehnaz K; Jiang, Qingwu; Mu, Li-Na; Rao, Jianyu; Wang, Hua; You, Nai-Chieh Y; Yu, Shun-Zhang; Zhao, Jin-Kou; Zhang, Zuo-Feng
Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95% CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR(adj) 2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility. PMID:24030569
Marcy, Theodore W.; Stefanek, Michael; Thompson, Kimberly M.
Advances in genetics have increased our ability to assess an individual's genetic risk for disease. There is a hypothesis that genetic test results will motivate high-risk individuals to reduce harmful exposures, to increase their surveillance for disease, or to seek preventive treatments. However, genetic testing for genes associated with an increased risk of lung cancer would not change physicians' recommendations regarding smoking cessation. Limited studies suggest that test results that d...
Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Inherited Susceptibility to Cancer: Comparing Breast and Ovarian Cancers to Colon Cancers: Patents and Licensing for Breast, Ovarian and Colon Cancer Testing
Cook-Deegan, Robert; DeRienzo, Christopher; Carbone, Julia; Chandrasekharan, Subhashini; Heaney, Christopher; Conover, Christopher
Genetic testing for inherited susceptibility to breast and ovarian cancer can be compared to similar testing for colorectal cancer as a “natural experiment.” Inherited susceptibility accounts for a similar fraction of both cancers and genetic testing results guide decisions about options for prophylactic surgery in both sets of conditions. One major difference is that in the United States, Myriad Genetics is the sole provider of genetic testing, because it has sole control of relevant patents...
Full Text Available Ultraviolet radiation (UV contributes to a variety of skin diseases including inflammation, degenerative aging, and cancer. Historically, humans have been exposed to UV radiation mainly through occupational exposure; recreational UV exposure, however, has increased dramatically in recent years, because of outdoor leisure activities and to purposely tan for cosmetic purposes. Both UVB and UVA radiation have been shown to cause DNA damage and immunosuppression, the important forms of biological damage that lead to NMSC. Nonmelanoma skin cancer (NMSC is the most common malignancy, whose public health significance is often unrecognized which continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include photodynamic therapy, electrochemotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Among these, photodynamic therapy is a noninvasive technique with excellent cosmetic outcome and good curative results, when used in initial stages of skin cancers for superficial lesions. It is administered under numerous and significantly varied regimens and there are a wide range of cure rates reported, permitting treatment of large and multiple lesions with excellent cosmetic results. This is an overview of photodynamic applications especially for the treatment of NMSC, with a short focus on daylight modality.
Grinberg, Alex; Widmer, Giovanni
Knowledge of the within-host genetic diversity of a pathogen often has broad implications for disease management. Cryptosporidium protozoan parasites are among the most common causative agents of infectious diarrhoea. Current limitations of in vitro culture impose the use of uncultured isolates obtained directly from the hosts as operational units of Cryptosporidium genotyping. The validity of this practice is centred on the assumption of genetic homogeneity of the parasite within the host, and genetic studies often take little account of the within-host genetic diversity of Cryptosporidium. Yet, theory and experimental evidence contemplate genetic diversity of Cryptosporidium at the within-host scale, but this diversity is not easily identified by genotyping methods ill-suited for the resolution of DNA mixtures. We performed a systematic bibliographical search of the occurrence of within-host genetic diversity of Cryptosporidium parasites in epidemiological samples, between 2005 and 2015. Our results indicate that genetic diversity at the within-host scale, in the form of mixed species or intra-species diversity, has been identified in a large number (n=55) of epidemiological surveys of cryptosporidiosis in variable proportions, but has often been treated as a secondary finding and not analysed. As in malaria, there are indications that the scale of this diversity varies between geographical regions, perhaps depending on the prevailing transmission pathways. These results provide a significant knowledge base from which to draw alternative population genetic structure models, some of which are discussed in this paper. PMID:27021167
Pober, Barbara R.
Congenital diaphragmatic hernia (CDH) is a common and well-studied birth defect. The etiology of most cases remains unknown but increasing evidence points to genetic causation. The data supporting genetic etiologies which are detailed below include the association of CDH with recurring chromosome abnormalities, the existence of CDH-multiplex families, and the co-occurrence of CDH with additional congenital malformations.
Hayat Roshanai, Afsaneh
The overall aims of this thesis were to investigate psychological and behavioral effects of receiving cancer genetic counseling for breast, ovarian and colorectal cancer and/or with a family history of these cancer types and to determine whether counselees’ informational needs were met. Study I was performed 3-7 years post-counseling. Participants (n=214) reported a relatively high level of anxiety but a low level of depression compared to cancer patients in general. However, there was no ind...
Lindström, Linda Sofie
Cancer affects essentially everyone, directly or indirectly. The aim of this thesis was to study the genetic and environmental factors in cancer development and survival. Our studies were based on a record linkage between several Swedish population-based registries, principally the Multi-Generation Register, which records familial relationships, the Swedish Cancer Registry, and the Cause of Death Registry. In summary, the Swedish Family-Cancer database comprised over 11 mill...
Butt Salma; Harlid Sophia; Borgquist Signe; Ivarsson Malin; Landberg Göran; Dillner Joakim; Carlson Joyce; Manjer Jonas
Abstract Background Recent studies have identified several single-nucleotide polymorphisms (SNPs) associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk. Methods The Malmö Diet and Cancer Study (MDCS) included 17 035 female participants, from which 728 incident bre...
Forchetti, G; Suppa, M; Del Marmol, V
The risk of non-melanoma skin cancer (NMSC) is significantly increased in solid organ transplant recipients (SOTRs) due to the long-term immunosuppressive treatment. NMSCs can be more aggressive in SOTRs than in the general population, resulting in significantly higher morbidity and mortality. In contrast to the immunocompetent population, skin cancers in SOTRs are dominated by squamous cell carcinoma, followed by basal cell carcinoma. Life-long radiation exposure, male sex, fair skin, history of prior NMSC, genetic factors, age at transplant along with duration and extent of the immunosuppression therapy have been identified as risk factors for NMSC in SOTRs. Photo-protection, skin self-examination, early diagnosis and treatment of skin lesions, reduction of immunotherapy, switch to mammalian target-of-rapamycin inhibitors and chemoprevention with oral retinoids are effective measures for the reduction of the incidence of NMSC in such patients. PMID:25068224
Noori Daloii MR
Full Text Available "nThe prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer, and also the second leading cause of cancer death (after lung cancer among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.
Clear and unambiguous associations have been established between therapeutic exposures and specific complications. However, considerable interindividual variability is observed in the risk of developing an outcome for a given therapeutic exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the interindividual variability. This article provides a brief overview of the current knowledge about the role of genomic variation in the development of therapy-related complications. Relatively common outcomes with strong associations with therapeutic exposures, including cardiomyopathy, obesity, osteonecrosis, ototoxicity, and subsequent malignancies are discussed here. To develop a deeper understanding of the molecular underpinnings of therapy-related complications, comprehensive and near-complete collection of clinically annotated samples is critical. Methodologic issues such as study design, definition of the endpoints or phenotypes, identification of appropriate and adequately sized study population together with a reliable plan for collecting and maintaining high-quality DNA, and selection of an appropriate approach or platform for genotyping are also discussed. Understanding the etiopathogenetic pathways that lead to the morbidity is critical to developing targeted prevention and intervention strategies, optimizing risk-based health care of cancer survivors, thus minimizing chronic morbidities and improving quality of life. PMID:21980013
Núñez, Cristina; Capelo, José Luis; Igrejas, Gilberto; Alfonso, Amparo; Botana, Luis M; Lodeiro, Carlos
Breast cancer (BC) is generally classified based on the receptors overexpressed on the cell nucleus, which include hormone receptors such as progesterone (PR) and estrogen (ER), and HER2. Triple-negative breast cancer (TNBC) is a type of cancer that lacks any of these three types of receptor proteins (ER/PR/HER2). Tumor cells exhibit drug resistant phenotypes that decrease the efficacy of chemotherapeutic treatments. Generally, drug resistance has a genetic basis that is caused by an abnormal gene expression, nevertheless, there are several types of drug resistance: efflux pumps reducing the cellular concentration of the drug, alterations in membrane lipids that reduce cellular uptake, increased or altered drug targets, metabolic alteration of the drug, inhibition of apoptosis, repair of the damaged DNA, and alteration of the cell cycle checkpoints. The use of "combination therapy" is recognized as an efficient solution to treat human diseases, in particular, breast cancer. In this review, we give examples of different nanocarriers used to co-deliver multiple therapeutics (chemotherapeutic agent and nucleic acid) to drug-resistant tumor cells, and lastly, we give our recommendations for the future directions for the co-delivery treatments. PMID:27162073
Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets. Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding.
Alessandro Leone; Alberto Spada; Alberto Battezzati; Alberto Schiraldi; Junior Aristil; Simona Bertoli
Moringa oleifera is an interesting plant for its use in bioactive compounds. In this manuscript, we review studies concerning the cultivation and production of moringa along with genetic diversity among different accessions and populations. Different methods of propagation, establishment and cultivation are discussed. Moringa oleifera shows diversity in many characters and extensive morphological variability, which may provide a resource for its improvement. Great genetic variability is pres...
Baars, J. E.; van Dulmen, A M; Velthuizen, M. E.; Theunissen, E. B. M.; Vrouenraets, B.C.; Kimmings, A.N.; Dalen, T. van; van Ooijen, B; Witkamp, A.J.; van der Aa, M. A.; Ausems, M.G.E.M.
Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total ...
Baars, J. E.; van Dulmen, A M; Velthuizen, M. E.; Theunissen, E. B. M.; Vrouenraets, B.C.; Kimmings, A.N.; Dalen, T. van; van Ooijen, B; Witkamp, A.J.; van der Aa, M. A.; Ausems, M.G.E.M.
Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total ...
Beth Anderson; Jennifer McLosky; Elizabeth Wasilevich; Sarah Lyon-Callo; Debra Duquette; Glenn Copeland
Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS). Methods. Through the Michi...
Cragun, Deborah; Lewis, Courtney; Camperlengo, Lucia; Pal, Tuya
This article introduces the identification, prevention, and treatment of hereditary cancer as an important public health concern. Hereditary cancer research and educational outreach activities are used to illustrate how public health functions can help to achieve health benefits of genetic and genomic medicine. First, we evaluate genetic service delivery through triangulating patient and provider survey results which reveal variability among providers in hereditary cancer knowledge and genetic service provision. Second, we describe efforts we have made to assure competency among healthcare providers and to inform, educate and empower patients with regard to the rapidly evolving field of genomics and hereditary cancer. Lastly, key policy-issues raised by our experiences are discussed in the context of how they may help us to more effectively translate future genomic technologies into practice in order to attain population health benefits from genetic and genomic medicine.
Morley-Bunker, A; Walker, L C; Currie, M J; Pearson, J; Eglinton, T
Colorectal cancer (CRC) is a major health problem worldwide accounting for over a million deaths annually. While many patients with Stage II and III CRC can be cured with combinations of surgery, radiotherapy and chemotherapy, this is morbid costly treatment and a significant proportion will suffer recurrence and eventually die of CRC. Increased understanding of the molecular pathogenesis of CRC has the potential to identify high risk patients and target therapy more appropriately. Despite increased understanding of the molecular events underlying CRC development, established molecular techniques have only produced a limited number of biomarkers suitable for use in routine clinical practice to predict risk, prognosis and response to treatment. Recent rapid technological developments, however, have made genomic sequencing of CRC more economical and efficient, creating potential for the discovery of genetic biomarkers that have greater diagnostic, prognostic and therapeutic capabilities for the management of CRC. This paper reviews the current understanding of the molecular pathogenesis of CRC, and summarizes molecular biomarkers that surgeons will encounter in current clinical use as well as those under development in clinical and preclinical trials. New molecular technologies are reviewed together with their potential impact on the understanding of the molecular pathogenesis of CRC and their potential clinical utility in classification, diagnosis, prognosis and targeting of therapy. PMID:26990814
V. N. Pavlov
Full Text Available To reveal possible associations of the polymorphic variants of the cytochrome P450 and enzymes glutathione-S-transferase genes with the risk for bladder cancer (BC, the authors analyzed the frequency of genotypes and alleles at the polymorphic loci of the CYP1A1 (A2454G, GSTM1 (del, and GSTP1 (A313G genes in 208 patients diagnosed as having BC (104 patients with invasive BC and 104 with superficial BC and in 367 patients without identified oncopathology. The *1A*2C (OR = 3.42 and *2C*2С (OR = 6.98 genotypes, *2C (OR = 3.73 allele of the CYP1A1 gene and the GG (OR = 2.53 genotype of the GSTP1 gene were ascertained to be genetic markers for a risk for BC. The presence of the *2C (OR = 1.69 allele of the CYP1A1 gene, the G (OR = 2.40 allele and the AG genotype (OR = 2.40 of the GSTP1 gene was associated with the invasive forms of BC. There were no substantial differences in the distribution of the frequency of genotypes of the GSTM1 gene between the samples of patients and healthy individuals.
Salemink, Simone; Dekker, Nicky; Kets, Carolien M.; van der Looij, Erica; van Zelst-Stams, Wendy A. G.; Hoogerbrugge, Nicoline
During cancer genetic counseling, different items which counselors consider important are discussed. However, relatively little empirical evidence exists regarding the needs and preferences of counselees. In this study needs and preferences were assessed from counselees with a personal and/or family history of colorectal cancer (CRC), who were referred for genetic counseling regarding CRC. They received a slightly modified version of the QUOTE-GENEca questionnaire prior to their first visit t...
Kelly, Kimberly M.; Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D.; Leventhal, Howard; Andrykowski, Michael
Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheri...
Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.
Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...
Riel, E. van; Dulmen, S. van; Ausems, M.G.E.M.
Both physician and patient play a role in the referral process for cancer genetic counseling. Access to such counseling is not optimal because some eligible patients are not being reached by current referral practice. We aimed to identify factors associated with the initiator of referral. During a 7-month period, we recorded demographic characteristics like gender, personal and family history of cancer, ethnicity and eligibility for genetic testing for 406 consecutive counselees using a speci...
Patrick-Miller, Linda J.; Egleston, Brian L.; Fetzer, Dominique; Forman, Andrea; Bealin, Lisa; Rybak, Christina; Peterson, Candace; Corbman, Melanie; Albarracin, Julio; Stevens, Evelyn; Daly, Mary B.; Bradbury, Angela R.
Background Dissemination of genetic testing for disease susceptibility, one application of “personalized medicine”, holds the potential to empower patients and providers through informed risk reduction and prevention recommendations. Genetic testing has become a standard practice in cancer prevention for high-risk populations. Heightened consumer awareness of “cancer genes” and genes for other diseases (eg, cardiovascular and Alzheimer’s disease), as well as the burgeoning availability of inc...
Lee, Charmaine Pei Ling; Irwanto, Astrid; Salim, Agus; Yuan, Jian-Min; Liu, Jianjun; Koh, Woon Puay; Hartman, Mikael
Introduction Genetic variants for breast cancer risk identified in genome-wide association studies (GWAS) in Western populations require further testing in Asian populations. A risk assessment model incorporating both validated genetic variants and established risk factors may improve its performance in risk prediction of Asian women. Methods A nested case-control study of female breast cancer (411 cases and 1,212 controls) within the Singapore Chinese Health Study was conducted to investigat...
George Hripcsak; Rita Kukafka; Chung, Wendy K.; Casey Lynnette Overby
Personalized medicine is a model of healthcare that is predictive, personalized, preventive and participatory (“P4 Medicine”). Genetic counselors are an ideal group to study when designing tools to support cancer P4 Medicine activities more broadly. The goal for this work was to gain a better understanding of the information cancer genetic counselors seek from their patients to facilitate effective information exchange for discussing risk. This was an analysis of a qualitative data set from i...
I.I.H. van Oostrom (Iris)
textabstractCancer is generally feared because it is associated with death and severe physical suffering. It is one of the most common causes of death in the Netherlands. Breast and colon cancer are the most prevalent types of cancer among women. Frequently occurring types in men are cancer of colon
Full Text Available This article aims at providing a general overview of psychological interventions intended to promote psychological adjustment of children with cancer and their parents. To achieve this goal, we reviewed published articles between 1998-2010, using a combination of the following key words: psychosocial intervention, psychotherapy, trial, treatment, adjustment, wellbeing, adaptation, cancer, childhood cancer, pediatric cancer, anxiety and depression in the electronic databases: Psycinfo, Medline, Scielo, Lilacs, Psicodoc and Psyarticles. Fourteen articles were found and analyses show that most interventions had some efficacy in the psychological adjustment of children and their parents; nevertheless, there is a limited number of treatments that can in fact be considered effective. The convenience of psychological interventions is discussed and how they must comprehend strengths and the promotion of psychological health and should not be based solely on deficits and psychopathological models. Possibly, this reorientation will help fostering significant clinic changes regarding the stress associated to cancer and its treatment.
Légaré, France; Robitaille, Hubert; Gane, Claire; Hébert, Jessica; Labrecque, Michel; Rousseau, François
Background Knowledge translation (KT) interventions are attempts to change behavior in keeping with scientific evidence. While genetic tests are increasingly available to healthcare consumers in the clinic, evidence about their benefits is unclear and decisions about genetic testing are thus difficult for all parties. Objective We sought to identify KT interventions that involved decisions about genetic testing in the clinical context and to assess their effectiveness for improving decision making in terms of behavior change, increased knowledge and wellbeing. Methods We searched for trials assessing KT interventions in the context of genetic testing up to March 2014 in all systematic reviews (n = 153) published by two Cochrane review groups: Effective Practice and Organisation of Care (EPOC) and Consumers and Communication. Results We retrieved 2473 unique trials of which we retained only 28 (1%). Two EPOC reviews yielded two trials of KT interventions: audit and feedback (n = 1) and educational outreach (n = 1). Both targeted health professionals and the KT intervention they assessed was found to be effective. Four Consumers and Communication reviews yielded 26 trials: decision aids (n = 15), communication of DNA-based disease risk estimates (n = 7), personalized risk communication (n = 3) and mobile phone messaging (n = 1). Among these, 25 trials targeted only health consumers or patients and the KT interventions were found to be effective in four trials, partly effective in seven, and ineffective in four. Lastly, only one trial targeted both physicians and patients and was found to be effective. Conclusions More research on the effectiveness of KT interventions regarding genetic testing in the clinical context may contribute to patients making informed value-based decisions and drawing the maximum benefit from clinical applications of genetic and genomic innovations. PMID:26938633
Roč. 55, č. 6 (2009), s. 199-200. ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : genetically modified vaccines * cancer surgery and chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009
Schoeps, Anja; Rudolph, Anja; Seibold, Petra;
Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,47...
Kelly, Kimberly M.; Andrews, James E; Case, Donald O.; Allard, Suzanne L.; Johnson, J. David
Context: Research is limited regarding the potential of genetic testing for cancer risk in rural Appalachia. Purpose: This study examined perceptions of genetic testing in a population sample of Kentuckians, with a focus on Appalachian and rural differences. The goals were to examine cultural and psychosocial factors that may predict intentions to…
Lee, Jihyoun; Cho, Hyung Jung; Yoo, Han-Wook; Park, Sue K.; Yang, Jae Jeong; Kim, Sung-Won; Kang, Eunyoung; Ahn, Sei-Hyun; Lee, Soo-Jung; Suh, Young Jin; Kim, Sung Yong; Kim, Eun-Kyu; Moon, Nan Mo; Lee, Min Hyuk; ,
Purpose Systematic educational programs and genetic counseling certification courses for hereditary breast/ovarian cancer (HBOC) have not yet been introduced in Korea. We provided and evaluated the effects of genetic counseling education on Korean healthcare providers' knowledge, awareness, and counseling skills for patients at high risk of HBOC. Methods A 3-day educational program was conducted for healthcare providers who were interested in genetic counseling for patients at high risk of HB...
Rantala Johanna; Platten Ulla; Lindgren Gunilla; Nilsson Bo; Arver Brita; Lindblom Annika; Brandberg Yvonne
Abstract Background Counselees are more aware of genetics and seek information, reassurance, screening and genetic testing. Risk counseling is a key component of genetic counseling process helping patients to achieve a realistic view for their own personal risk and therefore adapt to the medical, psychological and familial implications of disease and to encourage the patient to make informed choices 12. The aim of this study was to conceptualize risk perception and anxiety about cancer in ind...
Watson, M.; Duvivier, V; Wade Walsh, M; Ashley, S; Davidson, J; Papaikonomou, M; Murday, V; Sacks, N; Eeles, R
The current study has two aims: (1) to look at people's recall of risk information after genetic counselling and (2) to determine the impact of receiving an audiotape of the genetic consultation on level of recall, cancer related worry, and women's uptake of risk management methods. Using a prospective randomised controlled design, subjects receiving an audiotape were compared with a standard consultation group. Participants were drawn from attenders at the genetic clinics of two London hospi...
Full Text Available Congenital renal cystic disease comprises a mixed group of developmental anomalies with different etiology, histology and clinical presentation. Progress in molecular genetics as well as use of prenatal and postnatal ultrasound contributed in early diagnosis and differentiation of congenital cystic diseases of the kidney. "nIn a retrospective study clinical and imaging findings of 131 infants and children with cystic diseases of kidney were collected with reviewing of clinical and imaging findings."nThis patient material is categorized in two groups: inherited renal cystic diseases and non-inherited cystic kidney diseases."nThe group of inherited renal diseases includes 28 patients with an autosomal dominant polycystic kidney disease (ADPKD. Eleven infants and children suffered from an autosomal recessive polycystic kidney disease (ARPKD. The remaining 6 of the 45 inherited cystic kidney diseases were 4 children with nephronophtisis and 2 with syndromal related cysts in kidney."nWithin the large group of patients with a non-inherited cystic kidney disease 79 infants and chil-dren were with one-sided non-functioning multicystic dysplastic kidney disease (MCKD. An ectopic ureter was found in 11 patients in this group and in 2 cases the ureter of the affected kidney was atretic. Lung hypoplasia was found in 2 cases with double-sided multicystic dysplastic kid-ney."nCystic nephroma (2 cases, renal cysts in malforma-tion syndromes (2 cases and the medullary sponge kidney (one case are the diagnosis of the remaining patients with a non-inherited renal cystic disease. "nSpecial attention should be payed to hepatic in-volvement in cases with ADPKD (hepatic cysts and ARPKD (liver fibrosis."nWithin the scope of this meeting the importance of early diagnostic and the incredible value of ultra-sound in prenatal and postnatal life will be empha-sized. The mode of inheritance in different genetic renal cystic diseases, complications and other addi
Ladics, G.S.; Holsapple, M.P.; Astwood, J.D.; Kimber, I.; Knippels, L.M.J.; Helm, R.M.; Dong, W.
There is a need to assess the safety of foods deriving from genetically modified (GM) crops, including the allergenic potential of novel gene products. Presently, there is no single in vitro or in vivo model that has been validated for the identification or characterization of potential food allerge
Leońska-Duniec, A; Ahmetov, I I; Zmijewski, P
Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary. PMID:27601774
Ahmetov, II; Zmijewski, P
Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary. PMID:27601774
Full Text Available
With over 500 000 annual deaths, Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide and a leading cause of death in developing countries where about 80% of the cases arise. Risk factors include chronic hepatitis infections (hepatitis B, (HBV and hepatitis C (HCV viruses, alcohol, dietary contaminants such as falatoxins The incidence shows important geographic variations, accor In southern Asia, HCC development is mainly related to the endemic Hepatitis B Virus (HBV infection, cases with hot spot mutation in codon 249 (249ser of TP53 tumor suppressor gene were also described and associated to a low-intermediate exposure rate to Aflatoxin B1 (AFB1. Presence of Hepatitis C Virus (HCV infection was also detected in 12 - 17% of HCC cases. Despite the increasing number of studies identifying viral/host interactions in viro-induced HCC or describing potential pathways for hepatocarcinogenesis, precise mechanism has not been identified so far. HBV was demonstrated to enhance hepatocarcinogenesis by different manners; HBV chronic infection is associated to active hepatitis (CAH and cirrhosis which are hepatic complications considered as early stage for HCC development. These complications mobilise the host immune response, the resulting inflammation initiates and selects the first genetic alteration at the origin of loss of cell control. Moreover, HBV can also promote carcinogenesis through genetic instability generated by its common integration in host DNA. HBV proteins, as HBx, was proven to interact with a variety of targets in the host cell including protein or host transcription factor such as, in particular, the p53 protein or the transcription factor E4F, which is implicated in growth, differenciation and senescence. Specific HBV mutations or distinct HBV genotypes are associated to higher risks factors for HCC or hepatic complications leading
Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M
The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. PMID:26324357
This thesis described the construction and screening of one of the first large scale RNAi libraries for use in human cells. Functional genetic screens with this library have led to the identification of novel cancer genes. These cancer genes function in several pathways including the p53 tumor suppr
Lee, Julie; Dahl, Morten; Nordestgaard, Børge G
Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in...
Zhu, Yitan; Xu, Yanxun; Helseth, Donald L.; Gulukota, Kamalakar; Yang, Shengjie; Pesce, Lorenzo L.; Mitra, Riten; Muller, Peter; Sengupta, Subhajit; Guo, Wentian; Foster, Ian; Bullock, JaQuel A.
Background: Genetic interactions play a critical role in cancer development. Existing knowledge about cancer genetic interactions is incomplete, especially lacking evidences derived from large-scale cancer genomics data. The Cancer Genome Atlas (TCGA) produces multimodal measurements across genomics and features of thousands of tumors, which provide an unprecedented opportunity to investigate the interplays of genes in cancer. Methods: We introduce Zodiac, a computational tool and resource to integrate existing knowledge about cancer genetic interactions with new information contained in TCGA data. It is an evolution of existing knowledge by treating it as a prior graph, integrating it with a likelihood model derived by Bayesian graphical model based on TCGA data, and producing a posterior graph as updated and data-enhanced knowledge. In short, Zodiac realizes “Prior interaction map + TCGA data → Posterior interaction map.” Results: Zodiac provides molecular interactions for about 200 million pairs of genes. All the results are generated from a big-data analysis and organized into a comprehensive database allowing customized search. In addition, Zodiac provides data processing and analysis tools that allow users to customize the prior networks and update the genetic pathways of their interest. Zodiac is publicly available at www.compgenome.org/ZODIAC. Conclusions: Zodiac recapitulates and extends existing knowledge of molecular interactions in cancer. It can be used to explore novel gene-gene interactions, transcriptional regulation, and other types of molecular interplays in cancer.
E1Z11 is a study to determine whether certain genetic information can predict which breast cancer patients will discontinue treatment with AIs due to the development of musculoskeletal symptoms (MSS). Women with stage 1-111 breast cancer who are prescribed the aromatase inhibitor anastrozole as treatment may join. |
Szulkin, Robert; Whitington, Thomas; Eklund, Martin;
BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate ca...
Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki;
BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. M...
Edenir I. Palmero
Full Text Available In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9% reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8% had an estimated lifetime risk of breast cancer ³ 20% and 214 (23.7% had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%. The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65. These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3% indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers.
Sheppard, Vanessa B.; Graves, Kristi D.; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia
Genetic counseling and testing for hereditary breast cancer have the potential benefit of early detection and early interventions in African American women. However, African American women have low use of these services compared to White women. We conducted two focus groups with African American women diagnosed with breast cancer (affected group, n=13) and women with at least one first-degree relative with breast/ovarian cancer (unaffected group, n= 8). A content analysis approach was employe...
Einarsdóttir, Kristjana; Darabi, Hatef; Li, Yi; Low, Yen Ling; Li, Yu Qing; Bonnard, Carine; Sjölander, Arvid; Czene, Kamila; Wedrén, Sara; Liu, Edison T.; Hall, Per; Humphreys, Keith; Liu, Jianjun
Introduction Oestrogen exposure is a central factor in the development of breast cancer. Oestrogen receptor alpha (ESR1) is the main mediator of oestrogen effect in breast epithelia and has also been shown to be activated by epidermal growth factor (EGF). We sought to determine if common genetic variation in the ESR1 and EGF genes affects breast cancer risk, tumour characteristics or breast cancer survival. Methods We genotyped 157 single nucleotide polymorphisms (SNPs) in ESR1 and 54 SNPs in...
AL-QASEM, ABEER J.; Toulimat, Mohamed; Abdelmoneim M Eldali; Tulbah, Asma; Al-Yousef, Nujoud; Al-Daihan, Sooad K; Al-Tassan, Nada; Al-Tweigeri, Taher; ABOUSSEKHRA, ABDELILAH
Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain ...
Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B;
Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and.......5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry....
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George, Angela; Riddell, Daniel; Seal, Sheila; Talukdar, Sabrina; Mahamdallie, Shazia; Ruark, Elise; Cloke, Victoria; Slade, Ingrid; Kemp, Zoe; Gore, Martin; Strydom, Ann; Banerjee, Susana; Hanson, Helen; Rahman, Nazneen
Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases. PMID:27406733
Labouisse Jean-Pierre; Sileye Tiata; Morin Jean-Paul; Hamelin Chantal; Baudouin Luc; Bourdeix Roland; Rouzière André
From 1962 to 2002, at the Saraoutou research station on the island of Santo in Vanuatu, genetic improvement work was undertaken to increase the productivity of coconut plantations, which, through copra exports, were the country’s main wealth in the last century. Beginning with two Vanuatu Tall (VTT) populations collected near the station, four mass selection cycles by open pollination or intercrossing have resulted in Elite Vanuatu Tall populations intended for distribution to farmers. The st...
Bujarski, Jozef J.
RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA–RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. ...
Leone, Alessandro; Spada, Alberto; Battezzati, Alberto; Schiraldi, Alberto; Aristil, Junior; Bertoli, Simona
Moringa oleifera is an interesting plant for its use in bioactive compounds. In this manuscript, we review studies concerning the cultivation and production of moringa along with genetic diversity among different accessions and populations. Different methods of propagation, establishment and cultivation are discussed. Moringa oleifera shows diversity in many characters and extensive morphological variability, which may provide a resource for its improvement. Great genetic variability is present in the natural and cultivated accessions, but no collection of cultivated and wild accessions currently exists. A germplasm bank encompassing the genetic variability present in Moringa is needed to perform breeding programmes and develop elite varieties adapted to local conditions. Alimentary and medicinal uses of moringa are reviewed, alongside the production of biodiesel. Finally, being that the leaves are the most used part of the plant, their contents in terms of bioactive compounds and their pharmacological properties are discussed. Many studies conducted on cell lines and animals seem concordant in their support for these properties. However, there are still too few studies on humans to recommend Moringa leaves as medication in the prevention or treatment of diseases. Therefore, further studies on humans are recommended. PMID:26057747
Full Text Available Personalized medicine is a model of healthcare that is predictive, personalized, preventive and participatory (“P4 Medicine”. Genetic counselors are an ideal group to study when designing tools to support cancer P4 Medicine activities more broadly. The goal for this work was to gain a better understanding of the information cancer genetic counselors seek from their patients to facilitate effective information exchange for discussing risk. This was an analysis of a qualitative data set from interviews of eight cancer genetic counselors, recruited from three institutions. Genetic counselors at each site were interviewed using a semi-structured, open-ended questionnaire. A selective coding approach was used to determine major themes associated with genetic counseling information needs for communicating risk. We generated a model for understanding categories of genetic counseling information needs to support risk communication activities. Common activities for risk communication included risk assessment and tailoring communication. Categories of information needs included: (a clinical patient characteristics, (b social and cognitive patient characteristics and (c patient motivation and goals for the genetic counseling session. A logical next step is for this model to inform the design of software systems for pre-visit patient planning and delivering just-in-time educational information to facilitate cancer risk communication activities.
Sweeney, Shannon M; Hastrup, Janice L; Hyland, Andrew; Rivard, Cheryl
The purpose of this study is to assess changes since the launch of the US Surgeon General's campaign in the public's beliefs about the role of genetics in the etiology of cancer, as well as changes in recording family health history. We conducted a survey of 480 Western New York adults, assessing: (1) experiences with cancer, (2) beliefs about cancer and genetics, and (3) practices of recording family health history. Most respondents were aware of the importance of family history. The sample also showed increased knowledge about cancer and genetics compared with a previous survey. However, only 7 % kept written records that included medical conditions, which was not different from a previous survey. Time constraints, apathy, and reluctance to find out negative health information were the most reported barriers. Results suggest a need for continued education of the public, with increased emphasis on written family health records. PMID:25976378
As the leading organization representing cancer specialists involved in patient care and clinical research, the American Society of Clinical Oncology (ASCO) reaffirms its commitment to integrating cancer risk assessment and management, including molecular analysis of cancer predisposition genes, into the practice of oncology and preventive medicine. The primary goal of this effort is to foster expanded access to, and continued advances in, medical care provided to patients and families affected by hereditary cancer syndromes. The 1996 ASCO Statement on Genetic Testing for Cancer Susceptibility set forth specific recommendations relating to clinical practice, research needs, educational opportunities, requirement for informed consent, indications for genetic testing, regulation of laboratories, and protection from discrimination, as well as access to and reimbursement for cancer genetics services. In updating this Statement, ASCO endorses the following principles: Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. ASCO recommends that genetic testing only be done in the setting of pre- and post-test counseling, which should include discussion of possible risks and benefits of cancer early detection and prevention modalities. Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that
Half of the familial aggregation of ovarian cancer can't be explained by any known risk genes, suggesting the existence of other genetic risk factors. Some of these unknown factors may not be traditional protein encoding genes. MicroRNA (miRNA) plays a critical role in tumorigenesis, but it is still unknown if variants in miRNA genes lead to predisposition to cancer. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis in familial ovarian cancer, we screened for genetic variants in thirty selected miRNA genes, which are predicted to regulate key ovarian cancer genes and are reported to be misexpressed in ovarian tumor tissues, in eighty-three patients with familial ovarian cancer. All of the patients are non-carriers of any known BRCA1/2 or mismatch repair (MMR) gene mutations. Seven novel genetic variants were observed in four primary or precursor miRNA genes. Among them, three rare variants were found in the precursor or primary precursor of the miR-191 gene. In functional assays, the one variant located in the precursor of miR-191 resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-191. In further analysis, we found that this particular variant exists in five family members who had ovarian cancer. Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer
Dhananjaya, B L; Sivashankari, P R
Snake venom is a complex mixture of biologically and pharmacologically active components, comprising hydrolytic enzymes, non-enzymatic proteins/peptides, and small amounts of organic and inorganic molecules. The venom components are known to vary with geographic location, season, species and age of the snakes. The role of the venom in the snake is not primarily for self-defense, but in prey immobilization and its subsequent digestion. Hence, several digestive enzymes in venoms, in addition to their hydrolytic activity have evolved to interfere in diverse physiological processes that help in the immobilization of prey/victim. As snake components are capable of modulating the physiological response of envenomated prey/victim, they show promise as potential pharmacological tools, as drug leads and in diagnostic applications. This, in a practical sense to be a reality has to be linked to the advances in toxinology that provide investigators with an understanding of the pharmacodynamics of toxins together with improved understanding of the etiology of many human diseases and identification of potential sites for therapeutic intervention. This review aims at providing an overview on snake venom toxins and their derivatives that have potential anti-angiogenic effects for cancer treatment. Some of the anti-angiogenic components of snake venom like Snake venom metalloproteinases (SVMPs), Disintegrins, Phospholipases A2 (PLA2), CType Lectins (CLP), Vascular Apoptosis inducing Proteins (VAP) and L-Amino Acid Oxidases (LAAO) are discussed. This review aims at giving an overall view of these molecules and their mechanism of action as an effective antiangiogenic agent towards the treatment of cancer. PMID:25714377
Brandt-Rauf, Sherry I; Raveis, Victoria H; Drummond, Nathan F; Conte, Jill A; Rothman, Sheila M
We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay-Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy. PMID:17018815
K S Guttal
Full Text Available According to World Health Organisation statistics, individuals of the Indian subcontinent have the highest prevalence of orofacial cancer. Surgery, radiation, chemotherapy or combination therapies are commonly administered treatment modalities for treatment of oral cancer. Surgical resection can be mutilating, disfiguring and may deeply affect self-image of patients. Orofacial defects have unique limitations and challenges. A coordinated effort from the surgeon, oral physician and the maxillofacial prosthodontist to treat such patients is the need of the hour. This article presents an overview of the orofacial rehabilitation of postcancer treatments along with case reports.
Petzel, Sue v.; Vogel, Rachel Isaksson; Bensend, Tracy; Leininger, Anna; Argenta, Peter A.; Geller, Melissa A.
Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04–8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referr...
Full Text Available Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism’s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy.
Nimptsch, Katharina; Aleksandrova, Krasimira; Boeing, Heiner;
women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of...... the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 µg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings...... of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development....
Robert P Young
Full Text Available BACKGROUND: Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: We screened 157 candidate single nucleotide polymorphisms (SNP in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases and identified 30 SNPs associated with either the healthy smokers (protective or lung cancer (susceptibility phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk. CONCLUSIONS/SIGNIFICANCE: Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.
Santos, Erika Maria Monteiro; Edwards, Quannetta T; Floria-Santos, Milena;
PURPOSE: The article aims to introduce nurses to how genetics-genomics is currently integrated into cancer care from prevention to treatment and influencing oncology nursing practice. ORGANIZING CONSTRUCT: An overview of genetics-genomics is described as it relates to cancer etiology, hereditary...... cancer syndromes, epigenetics factors, and management of care considerations. METHODS: Peer-reviewed literature and expert professional guidelines were reviewed to address concepts of genetics-genomics in cancer care. FINDINGS: Cancer is now known to be heterogeneous at the molecular level, with genetic......: Rapidly developing advances in genetics-genomics are changing all aspects of cancer care, with implications for nursing practice. CLINICAL RELEVANCE: Nurses can educate cancer patients and their families about genetic-genomic advances and advocate for use of evidence-based genetic-genomic practice...
Yadav, Anu; Gupta, Annapurna; Rastogi, Neeraj; Agrawal, Sushma; Kumar, Ashok; Kumar, Vijay; Mittal, Balraj
Genes important to stem cell progression have been involved in the genetics and clinical outcome of cancers. We investigated germ line variants in cancer stem cell (CSC) genes to predict susceptibility and efficacy of chemoradiotherapy treatment in gallbladder cancer (GBC) patients. In this study, we assessed the effect of SNPs in CSC genes (surface markers CD44, ALCAM, EpCAM, CD133) and (molecular markers NANOG, SOX-2, LIN-28A, ALDH1A1, OCT-4) with GBC susceptibility and prognosis. Total 610 GBC patients and 250 controls were genotyped by using PCR-RFLP, ARMS-PCR, and TaqMan allelic discrimination assays. Chemotoxicity graded 2-4 in 200 patients and tumor response was recorded in 140 patients undergoing neoadjuvant chemotherapy (NACT). Differences in genotype and haplotype frequency distributions were calculated by binary logistic regression. Gene-gene interaction model was analyzed by generalized multifactor dimensionality reduction (GMDR). Overall survival was assessed by Kaplan-Meier survival curve and multivariate Cox-proportional methods. ALCAM Ars1157Crs10511244 (P = 0.0035) haplotype was significantly associated with GBC susceptibility. In GMDR analysis, ALCAM rs1157G>A, EpCAM rs1126497T>C emerged as best significant interaction model with GBC susceptibility and ALDH1A1 rs13959T>G with increased risk of grade 3-4 hematological toxicity. SOX-2 rs11915160A>C, OCT-4 rs3130932T>G, and NANOG rs11055786T>C were found best gene-gene interaction model for predicting response to NACT. In both Cox-proportional and recursive partitioning ALCAM rs1157GA+AA genotype showed higher mortality and hazard ratio. ALCAM gene polymorphisms associated with GBC susceptibility and survival while OCT-4, SOX-2, and NANOG variants showed an interactive role with treatment response. PMID:26318430
This article examines how cancer genetics has emerged as a focus for research and healthcare in Cuba and Brazil. Drawing on ethnographic research undertaken in community genetics clinics and cancer genetics services, the article examines how the knowledge and technologies associated with this novel area of healthcare are translated and put to work by researchers, health professionals, patients and their families in these two contexts. It illuminates the comparative similarities and differences in how cancer genetics is emerging in relation to transnational research priorities, the history and contemporary politics of public health and embodied vulnerability to cancer that reconfigures the scope and meaning of genomics as "personalised" medicine. PMID:27008076
Roberts, Nicholas J.; Norris, Alexis L.; Petersen, Gloria M.; Bondy, Melissa L.; Brand, Randall; Gallinger, Steven; Kurtz, Robert C.; Olson, Sara H.; Rustgi, Anil K.; Schwartz, Ann G.; Stoffel, Elena; Syngal, Sapna; Zogopoulos, George; Ali, Syed Z.; Axilbund, Jennifer; Chaffee, Kari G.; Chen, Yun-Ching; Cote, Michele L.; Childs, Erica J.; Douville, Christopher; Goes, Fernando S.; Herman, Joseph M.; Iacobuzio-Donahue, Christine; Kramer, Melissa; Makohon-Moore, Alvin; McCombie, Richard W.; McMahon, K. Wyatt; Niknafs, Noushin; Parla, Jennifer; Pirooznia, Mehdi; Potash, James B.; Rhim, Andrew D.; Smith, Alyssa L.; Wang, Yuxuan; Wolfgang, Christopher L.; Wood, Laura D.; Zandi, Peter P.; Goggins, Michael; Karchin, Rachel; Eshleman, James R.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.; Klein, Alison P.
Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genome of 638 familial pancreatic cancer patients. We also sequenced the exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types. PMID:26658419
Full Text Available Background: Synchronous cancers have occasionally been detected at initial diagnosis among patients with breast and ovarian cancer. However, simultaneous coexistence and diagnosis of breast and pancreas cancer has not previously been reported. Case Report: Paternal transmission of a germline BRCA2 mutation to a patient who was diagnosed at age 40 with locally advanced breast and pancreas cancer is presented. Somatic genomic analysis of both cancers with next-generation DNA sequencing confirmed the germline result and reported a variety of variants of unknown significance alterations, of which two were present in both the breast and pancreas cancers. Discussion: The possibility that genomic alterations could have been responsible for modulating the phenotypic or clinical expression of this rare presentation is considered. The authors call attention to the practice of privatizing the clinicogenetic information gained from genetic testing and call for health policy that will facilitate sharing in order to advance the outcomes of patients diagnosed with hereditary cancers.
Danish, Qazi; Mokhdomi, Taseem A; Bukhari, Shoiab; Ahmad, Raies
Lung cancer is the major cause of cancer-related mortality worldwide owing to its late-stage detection and aggressive behavior. Epidemiologically, several genetic and epigenetic factors contribute to the development of lung cancer. Angiogenesis, a critical process in tumor progression has become an important target for anti-cancer therapy particularly in lung cancer. Besides commercially available angiogenic inhibitors, numerous anti-angiogenic therapies have been developed to limit tumor growth, although, most of them have not proved beneficial in terms of long-term survival. Despite, logical advances in treatment strategies, NSCLC still remains a major health concern due to poor prognosis of the diseases state. This calls for a comprehensive analysis of signaling processes governing tumor angiogenesis and treatment options available thereof for development of a sustainable strategy to control cancer. In this review, several aspects of lung cancer have been discussed starting from its pathological characterization to the development of modern therapeutics. PMID:26406951
Wu, Yirong; Abbey, Craig K.; Liu, Jie; Ong, Irene; Peissig, Peggy; Onitilo, Adedayo A.; Fan, Jun; Yuan, Ming; Burnside, Elizabeth S.
Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case-control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low-penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naïve Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value < 0.001). A better understanding of relative predictive capability of genetic variants and mammography data may benefit clinicians and patients to make appropriate decisions about breast cancer screening, prevention, and treatment in the era of precision medicine.
Peter M.K.Westcott; Minh D.To
Mutational activation of KRAS is a common oncogenic event in lung cancer and other epithelial cancer types.Efforts to develop therapies that counteract the oncogenic effects of mutant KRAS have been largely unsuccessful,and cancers driven by mutant KRAS remain among the most refractory to available treatments.Studies undertaken over the past decades have produced a wealth of information regarding the clinical relevance of KRAS mutations in lung cancer.Mutant Kras-driven mouse models of cancer,together with cellular and molecular studies,have provided a deeper appreciation for the complex functions of KRAS in tumorigenesis.However,a much more thorough understanding of these complexities is needed before clinically effective therapies targeting mutant KRAS-driven cancers can be achieved.
Yan WANG; Ye, Yuanqing; Lin, Jie; Meyer, Larissa; Wu, Xifeng; Lu, Karen; Liang, Dong
Ovarian cancer is one of the leading female cancers in the United States. Challenges remain in early diagnosis of this deadly disease. Matrix metalloproteinases (MMPs) family genes are paradoxically involved in cancer promotion and suppression. We hypothesize that genetic variants in MMP genes are associated with ovarian cancer development, so they could be potential markers for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer cases and 417 healthy controls, we geno...
Ridge, Yolanda; Panabaker, Karen; McCullum, Mary; Portigal-Todd, Cheryl; Scott, Jenna; McGillivray, Barbara
As demand for genetic counseling regarding hereditary cancer continues to grow, more efficient methods of providing this service must be explored. In this pilot study, group genetic counseling was offered to two different cohorts of women seeking genetic counseling for Hereditary Breast and Ovarian Cancer. Seven group sessions, designed to cover all aspects of an individual genetic counseling appointment, were conducted. Although patients were receptive to group genetic counseling, a significant proportion chose individual counseling when given the option. Advantages of group genetic counseling include shared experience and increased efficiency. Disadvantages include increased frustration at not being eligible for genetic testing, group influence on decision-making, privacy concerns, increased need for follow-up, and difficulty booking group appointments. Overall, the level of patient satisfaction with group genetic counseling was similar to that of individual counseling. The results of this pilot study suggest that further research is needed to determine whether group genetic counseling is an acceptable alternative to individual counseling. PMID:19127417
Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris; Ritchie, Graham R.S.; Creixell, Pau; Karchin, Rachel; Vazquez, Miguel; Fink, J. Lynn; Kassahn, Karin S.; Pearson, John V.; Bader, Gary; Boutros, Paul C.; Muthuswamy, Lakshmi; Ouellette, B.F. Francis; Reimand, Jüri; Linding, Rune; Shibata, Tatsuhiro; Valencia, Alfonso; Butler, Adam; Dronov, Serge; Flicek, Paul; Shannon, Nick B.; Carter, Hannah; Ding, Li; Sander, Chris; Stuart, Josh M.; Stein, Lincoln D.; Lopez-Bigas, Nuria
The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor, but only a minority drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype. PMID:23900255
Colorectal cancer (CRC) is the third most common cancer, and the second most common cause of cancer mortality. The aim of this thesis work was to gain novel insight into the molecular mechanisms behind CRC predisposition, as well as tumor progression and development. Microsatellite instability (MSI) arises due to a defective mismatch repair system and is characteristic for a subset of all CRCs. Here, we aimed to identify novel MSI target genes with potential oncogenic effects. We charact...
Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris;
The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu...... discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....
Yin Sun; Jiaoti Huang
@@ Takata et al.1 recently reported in Nature Genetics that they have identified five nove associated with prostate cancer in the Japanese population.Using most updated Illumina Quad BeadChip to genotype 3001 prostate cancer patients and 5415 control subjects,they identified263 single-nucleotide polymorphisms(SNPs)showing significant association with prostate cancer in Japan.Further analysis indicated that 80 SNPs reside in the previously known regions,and five of them are novel susceptibility loci associated with the prostate cancer.
Nakagawa, Hidewaki; Akamatsu, Shusuke; Takata, Ryo
It is evident that genetic factors play critical roles in prostate cancer development. GWAS (genome-wide association studies) in multiple ethnic groups have been identifying more than 100 loci or genes which was significantly associated with prostate cancer susceptibility. They include several loci at 8q24, prostate-specific gene, inflammation gene, and metabolism-related genes. Risk prediction for prostate cancer by combining multiple SNPs is still primitive and not sufficiently accurate for clinical use, but this model could have a potential to affect clinical decision when it is applied to patients with gray-zone PSA or very high risk of prostate cancer. PMID:26793876
Douma, Kirsten F L; Smets, Ellen M A; Allain, Dawn C
Non-genetic health professionals (NGHPs) have insufficient knowledge of cancer genetics, express educational needs and are unprepared to counsel their patients regarding their genetic test results. So far, it is unclear how NGHPs perceive their own communication skills. This study was undertaken to gain insight in their perceptions, attitudes and knowledge. Two publically accessible databases were used to invite NGHPs providing cancer genetic services to complete a questionnaire. The survey assessed: sociodemographic attributes, experience in ordering hereditary cancer genetic testing, attitude, knowledge, perception of communication skills (e.g. information giving, decision-making) and educational needs. Of all respondents (N = 49, response rate 11%), most have a positive view of their own information giving (mean = 53.91, range 13-65) and decision making skills (64-77% depending on topic). NGHPs feel responsible for enabling disease and treatment related behavior (89-91%). However, 20-30% reported difficulties managing patients' emotions and did not see management of long-term emotions as their responsibility. Correct answers on knowledge questions ranged between 41 and 96%. Higher knowledge was associated with more confidence in NGHPs' own communication skills (r(s) = .33, p = 0.03). Although NGHPs have a positive view of their communication skills, they perceive more difficulties managing emotions. The association between less confidence in communication skills and lower knowledge level suggests awareness of knowledge gaps affects confidence. NGHPs might benefit from education about managing client emotions. Further research using observation of actual counselling consultations is needed to investigate the skills of this specific group of providers. PMID:26590592
Suda, Kenichi; Tomizawa, Kenji; Mizuuchi, Hiroshi; Ito, Simon; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Yoshida, Tsukihisa; Okamoto, Tatsuro; Maehara, Yoshihiko; Yatabe, Yasushi; Mitsudomi, Tetsuya
Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged ≥75 years with those of patients aged ≤ 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis,...
Samantha B. Foley
Full Text Available Despite the potential of whole-genome sequencing (WGS to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176 and those without (n = 82. Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500 in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS. Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks.
Kaphingst, Kimberly A; McBride, Colleen M
Advances in the genetic basis of kidney disease may mean that genetic testing is increasingly important in reducing disease morbidity and mortality among patients. However, there is little research examining patient responses to genetic information for Mendelian and common kidney diseases. Existing research on kidney and other hereditary cancer syndromes can inform three major issues relevant to the nephrology context: (1) how patients understand their risk of disease following genetic counse...
Pinheiro, Ana; Neves, Fabiana; Lemos de Matos, Ana; Abrantes, Joana; van der Loo, Wessel; Mage, Rose; Esteves, Pedro José
Our knowledge of the lagomorph immune system remains largely based upon studies of the European rabbit (Oryctolagus cuniculus), a major model for studies of immunology. Two important and devastating viral diseases, rabbit hemorrhagic disease and myxomatosis, are affecting European rabbit populations. In this context, we discuss the genetic diversity of the European rabbit immune system and extend to available information about other lagomorphs. Regarding innate immunity, we review the most recent advances in identifying interleukins, chemokines and chemokine receptors, Toll-like receptors, antiviral proteins (RIG-I and Trim5), and the genes encoding fucosyltransferases that are utilized by rabbit hemorrhagic disease virus as a portal for invading host respiratory and gut epithelial cells. Evolutionary studies showed that several genes of innate immunity are evolving by strong natural selection. Studies of the leporid CCR5 gene revealed a very dramatic change unique in mammals at the second extracellular loop of CCR5 resulting from a gene conversion event with the paralogous CCR2. For the adaptive immune system, we review genetic diversity at the loci encoding antibody variable and constant regions, the major histocompatibility complex (RLA) and T cells. Studies of IGHV and IGKC genes expressed in leporids are two of the few examples of trans-species polymorphism observed outside of the major histocompatibility complex. In addition, we review some endogenous viruses of lagomorph genomes, the importance of the European rabbit as a model for human disease studies, and the anticipated role of next-generation sequencing in extending knowledge of lagomorph immune systems and their evolution. PMID:26399242
Wilde, R.F. de
The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery (pancr
Full Text Available Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.
Longacre, Mckenna; Snyder, Nicole A.; Housman, Genevieve; Leary, Meghan; Lapinska, Karolina; Heerboth, Sarah; Willbanks, Amber; Sarkar, Sibaji
Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance. PMID:27213343
Full Text Available The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be
Gallo, Eduardo F; Posner, Jonathan
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by developmentally inappropriate levels of inattention and hyperactivity or impulsivity. The heterogeneity of its clinical manifestations and the differential responses to treatment and varied prognoses have long suggested myriad underlying causes. Over the past decade, clinical and basic research efforts have uncovered many behavioural and neurobiological alterations associated with ADHD, from genes to higher order neural networks. Here, we review the neurobiology of ADHD by focusing on neural circuits implicated in the disorder and discuss how abnormalities in circuitry relate to symptom presentation and treatment. We summarise the literature on genetic variants that are potentially related to the development of ADHD, and how these, in turn, might affect circuit function and relevant behaviours. Whether these underlying neurobiological factors are causally related to symptom presentation remains unresolved. Therefore, we assess efforts aimed at disentangling issues of causality, and showcase the shifting research landscape towards endophenotype refinement in clinical and preclinical settings. Furthermore, we review approaches being developed to understand the neurobiological underpinnings of this complex disorder, including the use of animal models, neuromodulation, and pharmacoimaging studies. PMID:27183902
Genetically modified (GM) crops have been and continue to be a subject of controversy despite their rapid adoption by farmers where approved. For the last two decades, an important matter of debate has been their impact on pesticide use, particularly for herbicide-tolerant (HT) crops. Some claim that these crops bring about a decrease in herbicide use, while others claim the opposite. In fact, since 1996, most cultivated GMOs have been GMHT crops, which involve the use of an associated herbicide, generally glyphosate. In their very first years of adoption, HT crops often led to some decrease in herbicide use. However, the repetition of glyphosate-tolerant crops and of glyphosate only applications in the same fields without sufficient alternation and herbicide diversity has contributed to the appearance of glyphosate-resistant weeds. These weeds have resulted in a rise in the use of glyphosate and other herbicides. This article explores this situation and the impacts of herbicide-resistant weeds, using an interdisciplinary approach and drawing on recent data. The paper analyzes the spread of GMHT crops worldwide and their consequences on herbicide use in the USA in particular. It then addresses the global development of glyphosate-resistant weeds and their impact, particularly focusing on the USA. Finally, the last section explores how industry, farmers, and weed scientists are coping with the spread of resistant weeds. The concluding comments deal more widely with trends in GM crops.
Genetically modified (GM) crops have been and continue to be a subject of controversy despite their rapid adoption by farmers where approved. For the last two decades, an important matter of debate has been their impact on pesticide use, particularly for herbicide-tolerant (HT) crops. Some claim that these crops bring about a decrease in herbicide use, while others claim the opposite. In fact, since 1996, most cultivated GMOs have been GMHT crops, which involve the use of an associated herbicide, generally glyphosate. In their very first years of adoption, HT crops often led to some decrease in herbicide use. However, the repetition of glyphosate-tolerant crops and of glyphosate only applications in the same fields without sufficient alternation and herbicide diversity has contributed to the appearance of glyphosate-resistant weeds. These weeds have resulted in a rise in the use of glyphosate and other herbicides. This article explores this situation and the impacts of herbicide-resistant weeds, using an interdisciplinary approach and drawing on recent data. The paper analyzes the spread of GMHT crops worldwide and their consequences on herbicide use in the USA in particular. It then addresses the global development of glyphosate-resistant weeds and their impact, particularly focusing on the USA. Finally, the last section explores how industry, farmers, and weed scientists are coping with the spread of resistant weeds. The concluding comments deal more widely with trends in GM crops. PMID:26296738
Gallo, Eduardo F; Posner, Jonathan
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by developmentally inappropriate levels of inattention and hyperactivity or impulsivity. The heterogeneity of its clinical manifestations and the differential responses to treatment and varied prognoses have long suggested myriad underlying causes. Over the past decade, clinical and basic research efforts have uncovered many behavioural and neurobiological alterations associated with ADHD, from genes to higher order neural networks. Here, we review the neurobiology of ADHD by focusing on neural circuits implicated in the disorder and discuss how abnormalities in circuitry relate to symptom presentation and treatment. We summarise the literature on genetic variants that are potentially related to the development of ADHD, and how these, in turn, might affect circuit function and relevant behaviours. Whether these underlying neurobiological factors are causally related to symptom presentation remains unresolved. Therefore, we assess efforts aimed at disentangling issues of causality, and showcase the shifting research landscape towards endophenotype refinement in clinical and preclinical settings. Furthermore, we review approaches being developed to understand the neurobiological underpinnings of this complex disorder including the use of animal models, neuromodulation, and pharmaco-imaging studies. PMID:27183902
Kizuka, Yasuhiko; Taniguchi, Naoyuki
N-glycan, a fundamental and versatile protein modification in mammals, plays critical roles in various physiological and pathological events including cancer progression. The formation of N-glycan branches catalyzed by specific N-acetylglucosaminyltransferases [GnT-III, GnT-IVs, GnT-V, GnT-IX (Vb)] and a fucosyltransferase, Fut8, provides functionally diverse N-glycosylated proteins. Aberrations of these branches are often found in cancer cells and are profoundly involved in cancer growth, invasion and metastasis. In this review, we focus on the GlcNAc and fucose branches of N-glycans and describe how their expression is dysregulated in cancer by genetic and nongenetic mechanisms including epigenetics and nucleotide sugar metabolisms. We also survey the roles that these N-glycans play in cancer progression and therapeutics. Finally, we discuss possible applications of our knowledge on basic glycobiology to the development of medicine and biomarkers for cancer therapy. PMID:27136596
Full Text Available N-glycan, a fundamental and versatile protein modification in mammals, plays critical roles in various physiological and pathological events including cancer progression. The formation of N-glycan branches catalyzed by specific N-acetylglucosaminyltransferases [GnT-III, GnT-IVs, GnT-V, GnT-IX (Vb] and a fucosyltransferase, Fut8, provides functionally diverse N-glycosylated proteins. Aberrations of these branches are often found in cancer cells and are profoundly involved in cancer growth, invasion and metastasis. In this review, we focus on the GlcNAc and fucose branches of N-glycans and describe how their expression is dysregulated in cancer by genetic and nongenetic mechanisms including epigenetics and nucleotide sugar metabolisms. We also survey the roles that these N-glycans play in cancer progression and therapeutics. Finally, we discuss possible applications of our knowledge on basic glycobiology to the development of medicine and biomarkers for cancer therapy.
Kizuka, Yasuhiko; Taniguchi, Naoyuki
N-glycan, a fundamental and versatile protein modification in mammals, plays critical roles in various physiological and pathological events including cancer progression. The formation of N-glycan branches catalyzed by specific N-acetylglucosaminyltransferases [GnT-III, GnT-IVs, GnT-V, GnT-IX (Vb)] and a fucosyltransferase, Fut8, provides functionally diverse N-glycosylated proteins. Aberrations of these branches are often found in cancer cells and are profoundly involved in cancer growth, invasion and metastasis. In this review, we focus on the GlcNAc and fucose branches of N-glycans and describe how their expression is dysregulated in cancer by genetic and nongenetic mechanisms including epigenetics and nucleotide sugar metabolisms. We also survey the roles that these N-glycans play in cancer progression and therapeutics. Finally, we discuss possible applications of our knowledge on basic glycobiology to the development of medicine and biomarkers for cancer therapy. PMID:27136596
Guo, Qi; Schmidt, Marjanka; Kraft, Peter; Canisius, Sander; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet; Wang, Qing; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Kar, Siddhartha; Beesley, Jonathan; Dunning, Alison
Higher-level funding: The COGS project was funded through a European Commission?s Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009?223175). The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). ELAN Program of the University Hospital Erlangen (BBCC). Personal support: DFE is a Principal Research Fellow of Cancer Research...
Adam Hudson Buchanan
Full Text Available Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state of science regarding service delivery models such as telephone counseling, telegenetics and group counseling. Research on comparative effectiveness of these models in traditional individual, in-person genetic counseling has been promising for improving access to care in a manner acceptable to patients. Yet, it has not fully evaluated the short- and long-term patient- and system-level outcomes that will help answer the question of whether these models achieve the same beneficial psychosocial and behavioral outcomes as traditional cancer genetic counseling. We propose a research agenda focused on comparative effectiveness of available service delivery models and how to match models to patients and practice settings. Only through this rigorous research can clinicians and systems find the optimal balance of clinical quality, ready and secure access to care, and financial sustainability. Such research will be integral to achieving the promise of genomic medicine in oncology.
Buchanan, Adam Hudson; Rahm, Alanna Kulchak; Williams, Janet L
Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care, and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state of science regarding service delivery models, such as telephone counseling, telegenetics, and group counseling. Research on comparative effectiveness of these models in traditional individual, in-person genetic counseling has been promising for improving access to care in a manner acceptable to patients. Yet, it has not fully evaluated the short- and long-term patient- and system-level outcomes that will help answer the question of whether these models achieve the same beneficial psychosocial and behavioral outcomes as traditional cancer genetic counseling. We propose a research agenda focused on comparative effectiveness of available service delivery models and how to match models to patients and practice settings. Only through this rigorous research can clinicians and systems find the optimal balance of clinical quality, ready and secure access to care, and financial sustainability. Such research will be integral to achieving the promise of genomic medicine in oncology. PMID:27242960
Buchanan, Adam Hudson; Rahm, Alanna Kulchak; Williams, Janet L.
Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care, and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state of science regarding service delivery models, such as telephone counseling, telegenetics, and group counseling. Research on comparative effectiveness of these models in traditional individual, in-person genetic counseling has been promising for improving access to care in a manner acceptable to patients. Yet, it has not fully evaluated the short- and long-term patient- and system-level outcomes that will help answer the question of whether these models achieve the same beneficial psychosocial and behavioral outcomes as traditional cancer genetic counseling. We propose a research agenda focused on comparative effectiveness of available service delivery models and how to match models to patients and practice settings. Only through this rigorous research can clinicians and systems find the optimal balance of clinical quality, ready and secure access to care, and financial sustainability. Such research will be integral to achieving the promise of genomic medicine in oncology.
Full Text Available Abstract Background Despite the fact that genetic counseling in oncology provides information regarding objective risks, it can be found a contrast between the subjective and objective risk. The aims of this study were to evaluate the accuracy of the perceived risk compared to the objective risk estimated by the BRCApro computer model and to evaluate any associations between medical, demographic and psychological variables and the accuracy of risk perception. Methods 130 subjects were given medical-demographic file, Cancer and Genetic Risk Perception, Hospital Anxiety-Depression Scale. It was also computed an objective evaluation of the risk by the BRCApro model. Results The subjective risk was significantly higher than objective risk. The risk of tumour was overestimated by 56%, and the genetic risk by 67%. The subjects with less cancer affected relatives significantly overestimated their risk of being mutation carriers and made a more innacurate estimation than high risk subjects. Conclusion The description of this sample shows: general overestimation of the risk, inaccurate perception compared to BRCApro calculation and a more accurate estimation in those subjects with more cancer affected relatives (high risk subjects. No correlation was found between the levels of perception of risk and anxiety and depression. Based on our findings, it is worth pursuing improved communication strategies about the actual cancer and genetic risk, especially for subjects at "intermediate and slightly increased risk" of developing an hereditary breast and/or ovarian cancer or of being mutation carrier.
Wu, Yirong; Abbey, Craig K.; Liu, Jie; Ong, Irene; Peissig, Peggy; Onitilo, Adedayo A.; Fan, Jun; Yuan, Ming; Burnside, Elizabeth S.
Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case-control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low-penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naïve Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value breast cancer screening, prevention, and treatment in the era of precision medicine.
This review traces steps leading to malignant neoplastic transformation of rodent and human cells in culture and in vivo. Emphasis is placed on an abnormal response characterized by persistent chromatid damage following irradiation of cells in culture with X-rays or fluorescent light during G2 phase of the cell cycle. Evidence is presented that deficient or unbalanced DNA repair during G2 accounts for the abnormal response. This G2 repair deficiency can be inherited or acquired by normal tissue cells during the process of or following attainment of infinite lifespan. It appears as an early, possibly initiating step in neoplastic transformation. It characterizes all human tumor cells examined irrespective of histopathology or tissue of origin. It has a genetic basis. In an animal model, the BALB/c mouse, this phenotype is associated with genes on chromosomes 1 and 4. It characterizes skin fibroblasts and blood lymphocytes from individuals with genetic or familial conditions predisposing to cancer and can be used to identify clinically normal family members carrying a gene(s) for any one of the three cancer-prone genetic disorders studied to date. Furthermore, it can provide the basis of a test for carriers of genes predisposing to a high risk of cancer. We conclude that the G2 repair deficiency, whether inherited or acquired, is a prerequisite for cancer development and that it accounts for the genetic instability of the cancer cell. 167 refs
Jozef Julian Bujarski
Full Text Available RNA recombination is one of the driving forces of genetic variability in (+-strand RNA viruses. Various types of RNA-RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings along with nonreplicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (i How various factors modulate the ability of viral replicase to switch templates, (ii What is the intracellular location of RNA-RNA template switchings, (iii Mechanisms and factors responsible for non-replicative RNA recombination, (iv Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (v What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.
Abe, O; Abe, R; Enomoto, K; Kikuchi, K; Koyama, H; Masuda, H; Nomura, Y; Sakai, K; Sugimachi, K; Tominaga, T; Uchino, J; Yoshida, M; Haybittle, JL; Davies, C; Harvey, VJ; Holdaway, TM; Kay, RG; Mason, BH; Forbes, JF; Wilcken, N; Gnant, M; Jakesz, R; Ploner, M; Yosef, HMA; Focan, C; Lobelle, JP; Peek, U; Oates, GD; Powell, J; Durand, M; Mauriac, L; Di Leo, A; Dolci, S; Piccart, MJ; Masood, MB; Parker, D; Price, JJ; Hupperets, PSGJ; Jackson, S; Ragaz, J; Berry, D; Broadwater, G; Cirrincione, C; Muss, H; Norton, L; Weiss, RB; Abu-Zahra, HT; Portnoj, SM; Baum, M; Cuzick, J; Houghton, J; Riley, D; Gordon, NH; Davis, HL; Beatrice, A; Mihura, J; Naja, A; Lehingue, Y; Romestaing, P; Dubois, JB; Delozier, T; Mace-Lesec'h, J; Rambert, P; Andrysek, O; Barkmanova, J; Owen, [No Value; Meier, P; Howell, A; Ribeiro, GC; Swindell, R; Alison, R; Boreham, J; Clarke, M; Collins, R; Darby, S; Davies, C; Elphinstone, P; Evans, [No Value; Godwin, J; Gray, R; Harwood, C; Hicks, C; James, S; MacKinnon, E; McGale, P; McHugh, T; Mead, G; Peto, R; Wang, Y; Albano, J; de Oliveira, CF; Gervasio, H; Gordilho, J; Johansen, H; Mouridsen, HT; Gelman, RS; Harris, [No Value; Henderson, IC; Shapiro, CL; Andersen, KW; Axelsson, CK; Blichert-Toft, M; Moller, S; Mouridsen, HT; Overgaard, J; Overgaard, M; Rose, C; Cartensen, B; Palshof, T; Trampisch, HJ; Dalesio, O; de Vries, EGE; Rodenhuis, S; van Tinteren, H; Comis, RL; Davidson, NE; Gray, R; Robert, N; Sledge, G; Tormey, DC; Wood, W; Cameron, D; Chetty, U; Forrest, P; Jack, W; Rossbach, J; Klijn, JGM; Treurniet-Donker, AD; van Putten, WLJ; Costa, A; Veronesi, U; Bartelink, H; Duchateau, L; Legrand, C; Sylvester, R; van der Hage, JA; van de Velde, CJH; Cunningham, MP; Catalano, R; Creech, RH; Bonneterre, J; Fargeot, P; Fumoleau, P; Kerbrat, P; Namer, M; Jonat, W; Kaufmann, M; Schumacher, M; von Minckwitz, G; Bastert, G; Rauschecker, H; Sauer, R; Sauerbrei, W; Schauer, A; Schumacher, M; de Schryver, A; Vakaet, L; Belfiglio, M; Nicolucci, A; Pellegrini, F; Sacco, M; Valentini, M; McArdle, CS; Smith, DC; Galligioni, E; Boccardo, F; Rubagotti, A; Dent, DM; Gudgeon, CA; Hacking, A; Erazo, A; Medina, JY; Izuo, M; Morishita, Y; Takei, H; Fentiman, IS; Hayward, JL; Rubens, RD; Skilton, D; Graeff, H; Janicke, F; Meisner, C; Scheurlen, H; Kaufmann, M; von Fournier, D; Dafni, U; Fountzilas, G; Klefstrom, P; Blomqvist, C; Saarto, T; Margreiter, R; Asselain, B; Salmon, RJ; Vilcoq, [No Value; Arriagada, R; Hill, C; Laplanche, A; Le, MG; Spielmann, M; Bruzzi, P; Montanaro, E; Rosso, R; Sertoli, MR; Venturini, M; Amadori, D; Benraadt, J; Kooi, M; van de Velde, AO; van Dongen, JA; Vermorken, JB; Castiglione, M; Cavalli, F; Coates, A; Collins, J; Forbes, J; Gelber, RD; Goldhirsch, A; Lindtner, J; Price, KN; Rudenstam, CM; Senn, HJ; Bliss, JM; Chilvers, CED; Coombes, RC; Hall, E; Marty, M; Borovik, R; Brufman, G; Hayat, H; Robinson, E; Wigler, N; Bonadonna, G; Camerini, T; De Palo, G; Del Vecchio, M; Formelli, F; Valagussa, P; Martoni, A; Pannuti, F; Cocconi, G; Colozza, A; Camisa, R; Aogi, K; Takashima, S; Abe, O; Ikeda, T; Inokuchi, K; Kikuchi, K; Sawa, K; Sonoo, H; Korzeniowski, S; Skolyszewski, J; Ogawa, M; Yamashita, J; Bonte, J; Christiaens, R; Paridaens, R; Van den Boegart, W; Martin, P; Romain, S; Hakes, T; Hudis, CA; Norton, L; Wittes, R; Giokas, G; Kondylis, D; Lissaios, B; de la Huerta, R; Sainz, MG; Altemus, R; Cowan, K; Danforth, D; Lichter, A; Lippman, M; O'Shaughnessy, J; Pierce, LJ; Steinberg, S; Venzon, D; Zujewski, J; Paradiso, A; De Lena, M; Schittulli, F; Myles, JD; Pater, JL; Pritchard, KI; Nomura, Y; Anderson, S; Bass, G; Brown, A; Bryant, J; Costantino, J; Dignam, J; Fisher, B; Redmond, C; Wieand, S; Wolmark, N; Baum, M; Jackson, IM; Palmer, MK; Ingle, JN; Suman, VJ; Bengtsson, NO; Jonsson, H; Larsson, LG; Lythgoe, JP; Swindell, R; Kissin, M; Erikstein, B; Hannisdal, E; Jacobsen, AB; Varhaug, JE; Erikstein, B; Gundersen, S; Hauer-Jensen, M; Host, H; Jacobsen, AB; Nissen-Meyer, R; Blamey, RW; Mitchell, AK; Morgan, DAL; Robertson, JFR; Di Palma, M; Mathe, G; Misset, JL; Clark, RM; Levine, M; Morimoto, K; Sawa, K; Takatsuka, Y; Crossley, E; Harris, A; Talbot, D; Taylor, M; Cocconi, G; di Blasio, B; Ivanov, [No Value; Semiglazov, [No Value; Brockschmidt, J; Cooper, MR; Ueo, H; Falkson, CI; A'Hern, R; Ashley, S; Powles, TJ; Smith, IE; Yarnold, [No Value; Gazet, JC; Cocoran, N; Deshpande, N; di Martino, L; Douglas, P; Hacking, A; Host, H; Lindtner, A; Notter, G; Bryant, AJS; Ewing, GH; Firth, LA; Krushen-Kosloski, JL; Nissen-Meyer, R; Foster, L; George, WD; Stewart, HJ; Stroner, P; Malmstrom, P; Moller, TR; Ryden, S; Tengrup, [No Value; Tennvall-Nittby, L; Carstenssen, J; Dufmats, M; Hatschek, T; Nordenskjold, B; Soderberg, M; Carpenter, JT; Albain, K; Crowley, J; Green, S; Martino, S; Osborne, CK; Ravdin, PM; Glas, U; Johansson, U; Rutqvist, LE; Singnomklao, T; Wallgren, A; Castiglione, M; Goldhirsch, A; Maibach, R; Senn, HJ; Thurlimann, B; Brenner, H; Hercbergs, A; Yoshimoto, M; DeBoer, G; Paterson, AHG; Pritchard, KI; Meakin, JW; Panzarella, T; Pritchard, KI; Shan, Y; Shao, YF; Wang, [No Value; Zhao, DB; Boreham, J; Chen, ZM; Pan, HC; Peto, R; Bahi, J; Reid, M; Spittle, M; Deutsch, GP; Senanayake, F; Kwong, DLW; Bianco, AR; Carlomagno, C; De Laurentiis, M; De Placido, S; Buzdar, AU; Smith, T; Bergh, J; Holmberg, L; Liljegren, G; Nilsson, J; Seifert, M; Sevelda, P; Zielinsky, CC; Buchanan, RB; Cross, M; Royle, GT; Dunn, JA; Hills, RK; Lee, M; Morrison, JM; Spooner, D; Litton, A; Chlebowski, RT; Caffier, H
Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-anal
Rial, Nathaniel S; Zell, Jason A.; Cohen, Alfred M.; Gerner, Eugene W.
To reduce the morbidity and mortality from colorectal cancer, current clinical practice focuses on screening for early detection and polypectomy as a form of secondary prevention, complemented with surgical interventions when appropriate. No pharmaceutical agent is currently approved for use in clinical practice for the management of patients with risk of colorectal cancer. This article will review earlier attempts to develop pharmaceuticals for use in managing patients with sporadic or genet...
Full Text Available Abstract Background While some factors of breast morphology, such as density, are directly implicated in breast cancer, the relationship between breast size and cancer is less clear. Breast size is moderately heritable, yet the genetic variants leading to differences in breast size have not been identified. Methods To investigate the genetic factors underlying breast size, we conducted a genome-wide association study (GWAS of self-reported bra cup size, controlling for age, genetic ancestry, breast surgeries, pregnancy history and bra band size, in a cohort of 16,175 women of European ancestry. Results We identified seven single-nucleotide polymorphisms (SNPs significantly associated with breast size (p−8: rs7816345 near ZNF703, rs4849887 and (independently rs17625845 flanking INHBB, rs12173570 near ESR1, rs7089814 in ZNF365, rs12371778 near PTHLH, and rs62314947 near AREG. Two of these seven SNPs are in linkage disequilibrium (LD with SNPs associated with breast cancer (those near ESR1 and PTHLH, and a third (ZNF365 is near, but not in LD with, a breast cancer SNP. The other three loci (ZNF703, INHBB, and AREG have strong links to breast cancer, estrogen regulation, and breast development. Conclusions These results provide insight into the genetic factors underlying normal breast development and show that some of these factors are shared with breast cancer. While these results do not directly support any possible epidemiological relationships between breast size and cancer, this study may contribute to a better understanding of the subtle interactions between breast morphology and breast cancer risk.
Pieterse, A H; van Dulmen, A M; Beemer, F A; Bensing, J M; Ausems, M.G.E.M.
Little is known about the relation between communication during cancer genetic counseling and outcome. We assessed associations between counselor-counselee communication and counselee satisfaction, cognitions, anxiety, and fulfillment of major needs, corrected for pre-visit levels as appropriate. In total 171 consecutive new counselees, mainly referred for breast or colon cancer, received pre- and post-visit questionnaires assessing needs/fulfillment, knowledge, perceived control (PPC), anxie...
Chen, Fang; Chen, Gary K.; Millikan, Robert C.; John, Esther M; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Jennifer J Hu; Ziegler, Regina G.; Deming, Sandra L.; Bandera, Elisa V.; Nyante, Sarah; Palmer, Julie R.; Rebbeck, Timothy R.; Sue A Ingles
Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and re...
In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.
Siegelmann-Danieli, N; Buetow, K H
The activity of the aromatase enzyme, which converts androgens into oestrogens and has a major role in regulating oestrogen levels in the breast, is thought to be a contributing factor in the development of breast cancer. We undertook this study to assess the role of constitutional genetic variation in the human aromatase gene (Cyp19) in the development of this disease. Our genotyping of 348 cases with breast cancer and 145 controls (all Caucasian women) for a published tetranucleotide repeat...
Canine, Brenda F.; Wang, Yuhua; Hatefi, Arash
A novel multi-domain biopolymer was designed and genetically engineered with the purpose to target and transfect cancer cells. The biopolymer contains at precise locations: 1) repeating units of arginine and histidine to condense pDNA and lyse endosome membranes, 2) a HER2 targeting affibody to target cancer cells, 3) a pH responsive fusogenic peptide to destabilize endosome membranes and enhance endosomolytic activity of histidine residues, and 4) a nuclear localization signal to enhance tra...
Singer, Eric A; Bratslavsky, Gennady; Middelton, Lindsay; Srinivasan, Ramaprasad; Linehan, W. Marston
Kidney cancer is a heterogeneous disease comprised of a number of histologic subtypes, each associated with unique genetic mutations, clinical features, and sensitivity to treatment. By examining families affected with the hereditary kidney cancer syndromes von Hippel-Lindau, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, and Birt-Hogg-Dube', researchers have been able to identify the genes responsible for these syndromes. This work has revealed...
Prostate cancer (PCa) is the second most common cancer in men worldwide. However the etiology of this disease remains largely unclear. Both genetic and environmental factors seem to be involved in the pathogenesis. In the last years the role of reactive oxygen species (ROS) in deterioration of DNA, proteins, lipids of membrane cells has been demonstrated. Also external antioxidant factors such as vitamin C and vitamin E, melatonin, that intercept free radicals, play a role, preventing damage ...
Full Text Available Abstract Background An estimated 12% of females in the United States will develop breast cancer in their lifetime. Although, there are advances in treatment options including surgery and chemotherapy, breast cancer is still the second most lethal cancer in women. Thus, there is a clear need for better methods to predict prognosis for each breast cancer patient. With the advent of large genetic databases and the reduction in cost for the experiments, researchers are faced with choosing from a large pool of potential prognostic markers from numerous breast cancer gene expression profile studies. Methods Five microarray datasets related to breast cancer were examined using gene set analysis and the cancers were categorized into different subtypes using a scoring system based on genetic pathway activity. Results We have observed that significant genes in the individual studies show little reproducibility across the datasets. From our comparative analysis, using gene pathways with clinical variables is more reliable across studies and shows promise in assessing a patient's prognosis. Conclusions This study concludes that, in light of clinical variables, there are significant gene pathways in common across the datasets. Specifically, several pathways can further significantly stratify patients for survival. These candidate pathways should help to develop a panel of significant biomarkers for the prognosis of breast cancer patients in a clinical setting.
... Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Cancer Treatment Prostate Cancer Prevention Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient ...
... BRCA-related cancer. Recommendations have letter grades. The grades are based on the quality and strength of the evidence about the potential ... harmful mutations in the BRCA1 or BRCA2 genes. Grade ... two tubes connect a woman’s ovaries to her uterus. peritoneal Cancer that develops in ...
Jensen, Lars Henrik; Dysager, Lars; Lindebjerg, Jan;
validate our previously suggested clinically applicable strategy based on molecular characteristics for identifying which patients to refer for genetic counselling. The strategy was validated in an unselected cohort of 287 colorectal cancer patients. All tumours were tested for MLH1, PMS2, MSH2 and MSH6...... with hereditary cancer. It is feasible to perform a molecular screening to select patients for genetic counselling....
Hu, Dong Gui; Mackenzie, Peter I; McKinnon, Ross A; Meech, Robyn
Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID:26828111
Pathmanathan, N; Bilous, A Michael
Testing for HER2 positivity in breast cancer carries implications for prognosis and therapeutic response in patients. In recent times there have been numerous developments and refinements in the available technologies for HER2 testing. In addition to this, guidelines have been developed and modified in an attempt to improve reliability and accuracy of testing. Immunohistochemistry and FISH testing have been the most widely used methodology, and the technique which has the largest knowledge base. Some of the inherent disadvantages have prompted the development of newer brightfield techniques which overcome some of these issues. There is gathering experience with these emerging technologies. Despite efforts to optimise and standardise procedures there remains a small percentage of cases that continue to be unresolved, whether this be due to issues of polysomy of chromosome 17, other complex genetic changes or analytical/interpretative issues. An ideal method for the resolution of these equivocal results should be considered in a specialised testing/referral centre, and this may include karyotyping studies of chromosome 17 or multiple probes for chromosome 17 using fluorescence in situ hybridisation or multiplex ligation-dependent probe amplification.It is timely to review of some of the newer techniques available for routine testing and approaches for cases which prove difficult to resolve using conventional testing methodology. PMID:23111474
Sigurður Ingvarsson 1956
In this intense meeting, many exciting new molecular genetic approaches and findings in the cancer field were presented. It was obvious that much has been accomplished and the field of cancer molecular genetics will continue to provide new information and understanding regarding the complex nature of neoplastic disease. Some of these findings may lead to better diagnosis and treatment of cancer.
Full Text Available Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS. Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%. One hundred twenty-two (42.2% reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.
Zhang, Xiaoli; He, Nonggao; Gu, Dongsheng; Wickliffe, Jeff; Salazar, James; Boldogh, Istavan; Xie, Jingwu
Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C (XPC) are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog (Kras) or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, Kras(LA1), as a driver for lung cancer development in mice, we showed for the first time that mice with Kras(LA1) and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured cells, we demonstrated that induced expression of oncogenic KRAS(G12V) led to increased levels of reactive oxygen species (ROS) as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS. PMID:26554912
Zackrisson, Bjoern [Univ. Hospital, Lund (Sweden). Dept. of Oncology; Mercke, Claes; Strander, Hans; Wennerberg, Johan; Cavallin-Staahl, Eva
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for head and neck cancer is based on data from 39 randomized trials and 1 meta-analysis. In total, 40 scientific articles are included, involving 20,893 patients. The results were compared with those of a similar overview from 1996 including 79,174 patients. The conclusions reached can be summarized as follows: General, non-nasopharynx: Substantial evidence indicates that the tumour effect of radiotherapy can be increased by the concomitant administration of chemotherapeutic agents, particularly cisplatin and 5-fluorouracil. There is moderate evidence of a survival benefit of radiation combined with concomitant chemotherapy compared to radiation alone. However, the results are equivocal. There is substantial evidence in published studies for an increased frequency of severe acute side effects as a result of concomitant chemotherapy and radiotherapy. There are very few studies that allow any estimates of the risk for serious late side effects. There is a weak indication of an increased risk for serious fibrosis. Comment: The general quality of studies and the lack of information on serious side effects indicate a need for large, well-designed clinical studies with a reasonable follow-up. Larynx preservation studies: There is strong evidence that larynx preservation is possible in 50% of the patients surviving for 5 years with hypopharyngeal cancers when treated with neoadjuvant chemotherapy and radical radiotherapy. There is a non-significant trend for the overall survival being lower in non-surgically treated patients than in those treated with primary surgery and postoperative radiotherapy. Nasopharynx There is moderate evidence that patients with nasopharyngeal carcinomas
Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians
DeMarco, Tiffani A.; Peshkin, Beth N.; Mars, Bryn D.; Tercyak, Kenneth P.
Satisfaction is an important patient reported outcome of genetic counseling, as it is one of the elements used by professional organizations and health care accrediting bodies to determine the quality of professional work. However, empirical research on patient satisfaction with genetic counseling has been limited, partly due to the lack of standardized measures available to assess this construct. The purpose of this study was to conduct a psychometric analysis of a new satisfaction measure, ...
Cancers is defined as the uncontrolled cell divisions. Cell does not grow maturely and destined to uncontrolled cell growth. When these cells of lungs grow uncontrolled it is called lung cancer. Nowadays mortality rate due to lung cancer is increasing day by day. Many treatment and diagnoses are now a day’s available to deal with lung cancer. Here we disused different method for diagnosis the common types of lung cancer Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Small Cell Lung Cance...
Talukder, Asoke K.; Agarwal, Mahima; Buetow, Kenneth H.; Denèfle, Patrice P.
It is difficult for existing methods to quantify, and track the constant evolution of cancers due to high heterogeneity of mutations. However, structural variations associated with nucleotide number changes show repeatable patterns in localized regions of the genome. Here we introduce SPKMG, which generalizes nucleotide number based properties of genes, in statistical terms, at the genome-wide scale. It is measured from the normalized amount of aligned NGS reads in exonic regions of a gene. SPKMG values are calculated within OncoTrack. SPKMG values being continuous numeric variables provide a statistical metric to track DNA level changes. We show that SPKMG measures of cancer DNA show a normative pattern at the genome-wide scale. The analysis leads to the discovery of core cancer genes and also provides novel dynamic insights into the stage of cancer, including cancer development, progression, and metastasis. This technique will allow exome data to also be used for quantitative LOH/CNV analysis for tracking tumour progression and evolution with a higher efficiency. PMID:27412732
Talukder, Asoke K; Agarwal, Mahima; Buetow, Kenneth H; Denèfle, Patrice P
It is difficult for existing methods to quantify, and track the constant evolution of cancers due to high heterogeneity of mutations. However, structural variations associated with nucleotide number changes show repeatable patterns in localized regions of the genome. Here we introduce SPKMG, which generalizes nucleotide number based properties of genes, in statistical terms, at the genome-wide scale. It is measured from the normalized amount of aligned NGS reads in exonic regions of a gene. SPKMG values are calculated within OncoTrack. SPKMG values being continuous numeric variables provide a statistical metric to track DNA level changes. We show that SPKMG measures of cancer DNA show a normative pattern at the genome-wide scale. The analysis leads to the discovery of core cancer genes and also provides novel dynamic insights into the stage of cancer, including cancer development, progression, and metastasis. This technique will allow exome data to also be used for quantitative LOH/CNV analysis for tracking tumour progression and evolution with a higher efficiency. PMID:27412732
Martha L Slattery; Lundgreen, Abbie; Welbourn, Bill; Corcoran, Christopher; Wolff, Roger K.
Background Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. Methods We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. Results After adjustment for multiple compari...
Full Text Available The mTOR (mammalian target of rapamycin signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC. We chose the SNPs (n = 11 with the strongest association with risk (p<0.01 and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele = 0.85, 95% CI 0.78-0.94, p = 1.3 x 10⁻³ for rs546950 and OR(allele = 0.84, 95% CI 0.76-0.93, p = 5.6 x 10⁻⁴ for rs4955720. We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk. Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables. The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016). This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population
Full Text Available Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, ′HPV′, ′cervical′, ′CIN′, ′polymorphism(s′, ′cervical′ + FNx01the name of the geneFNx01 and ′HPV′ + FNx01the name of the geneFNx01. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals.
Roč. 18, č. 3 (2001), s. 475-478. ISSN 1019-6439 R&D Projects: GA MZd NC5526 Keywords : dendritic cells * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.330, year: 2001
Jackson, Jody; Rolnick, Cheri; Rahm, Alanna; Nekhlyudov, Larissa; Goddard, Katrina; Field, Terry; McCarty, Catherine; Nakasato, Cynthia; ROBLIN, DOUGLAS; Anderson, Christopher; Valdez, Rodolfo
Background and Aims: Little of what we know about the use of family history and genetic risk assessment services has been gathered from those engaged in counseling. To fill this gap, we conducted a survey to understand the processes of identifying and referring high-risk patients for genetic counseling and testing for familial cancer from the perspective of genetic service providers.
Dossus, Laure; Benusiglio, Patrick ,
While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004...
Bleiker, E. M. A.; Aaronson, N. K.; Menko, F. H.; Hahn, D. E. E.; van Asperen, C. J.; Rutgers, E. J. T.; ten Kate, L. P.; Leschot, N. J.
Individuals who received genetic counseling for cancer (N=36) provided feedback on the quality of services and identified areas for improvement. Reasons for counseling and need for psychosocial support are also considered. Generally high levels of satisfaction with care provided were found. Four areas for improvement are identified and discussed.…
Full Text Available Introduction: The advent of human genome project has lead to genetic tests that identify high-risk states for certain cancers. Many are privately marketed on the Internet. Despite the availability of tests, limited data has evaluated factors that lead to test uptake. The aim of the present study was to explore the attitudes of a cohort of new mothers towards uptake of a genetic cancer test with a 50% predictive value of cancer.Methods: A cross-sectional survey was undertaken. The project targeted women who had recently given birth at an Australian tertiary referral hospital. Women were asked about a theoretical blood test that detected an increased risk for the development of cancer. Attitudes and knowledge questionnaires were completed. Results: Of 232 consecutive women approached, 32 declined, giving a response rate of 86.2%. Only 63 (31.5% women stated they would have the test. Absence of religious belief, higher level of education, better knowledge of terms used in genetics, an absence of concern over emotional, employment and insurance discrimination and previous acceptance of Down syndrome screening in pregnancy were each associated with significantly higher rate of test uptake in univariate analysis (all pConclusion: Concern over discrimination and having made a prior decision to have genetic testing were the principal factors associated with decision-making.
Thingholm, Louise Bruun; Andersen, Lars; Makalic, Enes;
The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. H...
This case study is an in-depth examination of how Erika (a pseudonym) interpreted and understood her genetic test results for breast cancer susceptibility. Her experience is presented in the form of a biography, which was built from key passages retrieved from the semi structured interview the author conducted at Erika's home. The interview data…
Gaudet, Mia M; Kirchhoff, Tomas; Green, Todd;
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carri...
Full Text Available Rapamycin and its derivatives (rapalogs, a group of allosteric inhibitors of mammalian target of rapamycin (mTOR, have been actively tested in a variety of cancer clinical trials, and some have been approved by the Food and Drug Administration for the treatment of certain types of cancers. However, the single agent activity of these compounds in many tumor types remains modest. The mTOR axis is regulated by multiple upstream signaling pathways. Because the genes (e.g., PIK3CA, KRAS, PTEN, and LKB1 that encode key components in these signaling pathways are frequently mutated in human cancers, a subset of cancer types may be addicted to a given mutation, leading to hyperactivation of the mTOR axis. Thus, efforts have been made to demonstrate the potential impact of genetic alterations on rapalog-based or mTOR-targeted cancer therapy. This review will primarily summarize research advances in this direction.
Full Text Available INTRODUCTION: Non-Hispanic (nH Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors. METHODS: We used a panel of 100 ancestry informative markers (AIMs to estimate individual genetic ancestry in 656 women from the "Breast Cancer Care in Chicago" study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities. RESULTS: As expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54-0.92 among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56-0.95 among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02 and higher grade (p = 0.012 in nH Whites and later stage (p = 0.03 in nH Blacks. CONCLUSION: Non-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial
The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed.......The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed....
Christensen, Mette; Drago, Antonio
Comorbidity between cancer and psychiatric disorders including adjustment disorder, depressive disorders or angst can seriously influence the prognosis and the quality of life of patients. The identification of the psychological and biological profile of patients at risk for such comorbidity is n...
Summer L. Cox
Full Text Available Introduction. Appropriate use of genetic tests for population-based cancer screening, diagnosis of inherited cancers, and guidance of cancer treatment can improve health outcomes. We investigated clinicians’ use and knowledge of eight breast, ovarian, and colorectal cancer genetic tests. Methods. We conducted a randomized survey of 2,191 Oregon providers, asking about their experience with fecal DNA, OncoVue, BRCA, MMR, CYP2D6, tumor gene expression profiling, UGT1A1, and KRAS. Results. Clinicians reported low confidence in their knowledge of medical genetics; most confident were OB-GYNs and specialists. Clinicians were more likely to have ordered/recommended BRCA and MMR than the other tests, and OB-GYNs were twice as likely to have ordered/recommended BRCA testing than primary care providers. Less than 10% of providers ordered/recommended OncoVue, fecal DNA, CYP2D6, or UGT1A1; less than 30% ordered/recommended tumor gene expression profiles or KRAS. The most common reason for not ordering/recommending these tests was lack of familiarity. Conclusions. Use of appropriate, evidence-based testing can help reduce incidence and mortality of certain cancers, but these tests need to be better integrated into clinical practice. Continued evaluation of emerging technologies, dissemination of findings, and an increase in provider confidence and knowledge are necessary to achieve this end.
Widmark, Anders; Flodgren, Per; Damber, Jan Erik; Hellsten, Sverker; Cavallin-Staahl, Eva [Univ. Hospital, Malmoe (Sweden). Dept. of Oncology
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for urinary bladder cancer is based on data from 3 meta-analyses and 33 randomized trials. The studies include 4,333 patients. The results were compared with those of a similar overview from 1996 including 15,042 patients. The conclusions reached can be summarized as these points: There is moderate evidence for an overall survival benefit with preoperative radiotherapy followed by cystectomy compared to curative radiotherapy based on early studies (1964-1986). Since that time surgical as well as radiation techniques have developed considerably. Therefore, the conclusion may not be relevant to modern treatment of invasive urinary bladder carcinoma. There is only one small study reporting on curative radiotherapy where increased dose per fraction is compared with conventionally fractionated radiotherapy to the same total dose. Thus, no conclusions can be drawn concerning optimal fraction dose. A meta-analysis based on two studies on hyperfractionated radiotherapy gives moderate evidence of a survival benefit at 5 and 10 years and an increased local control rate compared with conventional fractionation. The documentation of local control and overall survival rate after split-course radiation treatment compared to continuous therapy is conflicting. No firm conclusions can be drawn. Four small and early studies have compared radiation treatment using neutrons with photon treatment. The reports favour therapy with photons with respect to overall treatment results. There is moderate evidence for this conclusion. There is fairly strong evidence in early studies that radiation treatment in combination with hyperbaric oxygen does not confer a treatment benefit compared to radiation in
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for non-small cell lung cancer (NSCLC) is based on data from 4 meta-analyses and 31 randomized trials. Moreover, data from 12 prospective studies, 12 retrospective studies and 6 other articles were used. In total, 65 scientific articles are included, involving 18,310 patients. The results were compared with those of a similar overview from 1996 including 28,172 patients. The conclusions reached can be summarized as follows: Extensive clinical experience indicates that radiotherapy for medically inoperable patients or patients refusing surgery with NSCLC stage I/II prolongs survival, 15-20% of these patients reaching long-term (5-year) survival. However, no randomized trials have addressed this issue. There is strong evidence that postoperative radiotherapy in radically resected stage I/II NSCLC does not prolong survival compared with observation alone. There is some evidence that continuous hyperfractionated accelerated radiotherapy (CHART) is associated with increased survival compared to conventional radiotherapy in locally advanced NSCLC and also in medically unfit patients with stage I/II NSCLC. However, the benefit is limited to squamous cell histology. There is strong evidence that combined modality treatment with platinum-based chemotherapy and radiotherapy, either neoadjuvant or concomitant, is superior to radiotherapy alone in terms of survival in locally advanced unresectable NSCLC and should be the standard of care in patients with good performance status. There is some evidence that concomitant chemo-radiotherapy is associated with increased survival compared with sequential chemo-radiotherapy, albeit at the price of increased toxicity. Comment: Combined chemo
Full Text Available Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of "snapshot" expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer.
Vadaparampil, Susan T; Scherr, Courtney L.; Cragun, Deborah; Malo, Teri L.; Pal, Tuya
Genetic counseling and testing for hereditary breast and ovarian cancer now includes practitioners from multiple healthcare professions, specialties, and settings. This study examined whether non-genetics professionals (NGPs), perform guideline-based patient intake and informed consent before genetic testing. NGPs offering BRCA testing services in Florida (n = 386) were surveyed about clinical practices. Among 81 respondents (response rate = 22%), approximately half reported: sometimes schedu...
Full Text Available Abstract Background Recent studies have identified several single-nucleotide polymorphisms (SNPs associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk. Methods The Malmö Diet and Cancer Study (MDCS included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR with 95% confidence intervals (CI. Results Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2, rs3803662 (TNRC9, rs12443621 (TNRC9, rs889312 (MAP3K1, rs3817198 (LSP1 and rs2107425 (H19. We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons. Conclusions The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.
Lawrence B Schook
Full Text Available There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.
The National Health Interview Survey (NHIS) Cancer Control Supplement (CCS) is administered every five years and focuses on knowledge, attitudes, and practices in cancer-related health behaviors, screening, and risk assessment.
The Long Island Breast Cancer Study Project is a multistudy effort to investigate whether environmental factors are responsible for breast cancer in Suffolk and Nassau counties, NY, as well as in Schoharie County, NY, and Tolland County, CT.
Mara Gladstone; Tin Tin Su
Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety.It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later.In this regard,it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays.Drosophila melanogaster has emerged as a potential whole animal model for drug screening.Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer.A recent review provides a comprehensive summary of drug screening in Drosophila,but with an emphasis on neurodegenerative disorders.Here,we review Drosophila screens in the literature aimed at cancer therapeutics.
Liou, Yu-Ligh; Zhang, Tao-Lan; Yan, Tian; Yeh, Ching-Tung; Kang, Ya-Nan; Cao, Lanqin; Wu, Nayiyuan; Chang, Chi-Feng; Wang, Huei-Jen; Yen, Carolyn; Chu, Tang-Yuan; Zhang, Yi; Zhang, Yu; Zhou, Honghao
Background Opportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy. Methods The delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methy...
Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy
Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case–control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and pr...
Jivarajani Parimal J
Full Text Available ABSTRACT: Tobacco is the single most important cause of avoidable morbidity and early mortality in many countries. In India approximately 700,000-900,000 new cancers are diagnosed every year. Nearly half of all cancers in men and one fifth of cancers in women are tobacco related cancers. The present study was conducted to examine the proportion of tobacco related cancers, their age distribution and geographical variations in Patan district, Gujarat. All new cases of tobacco related cancers diagnosed during the year 2011 were included in the study. Apart from Gujarat Cancer & Research Institute, cancer data were also obtained from government hospitals, private hospitals& consultants, pathology laboratories and death registration units of Patan district and other districts. During the year 2011, a total of 472 new cases (Males: 310; Females: 162 were registered. Among them 214 cases were tobacco related cancers with a male preponderance (189 cases. Majority of the cases were in the age group of 35-64 years. Tongue Cancer was the commonest site in both sexes. Patan taluka had highest tobacco related cancers. This study implies an urgent need for tobacco control among the population of Patan district as tobacco is the most common risk factor of cancer occurrence.
Vidal, Joao Paulo C B; Felix, Shayany Pinto; Chaves, Cláudia B P; Patury, Patrícia; Franco, Vanessa F; de Morais, Evaneide A; de Carvalho, Neile A; Carvalho, Aurenice C L; Almeida Neto, Olimpio F; Vieira, Lina Maria T M; Correa, Flavia Miranda; Martins, Luís Felipe Leite; Negrão, Antonio; de Almeida, Liz Maria; Moreira, Miguel Angelo Martins
Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18. J. Med. Virol. 88:1279-1287, 2016. © 2015 Wiley Periodicals, Inc. PMID:26694554
Full Text Available Qicai Liu1,2, Ailin Liu3,4, Feng Gao5, Shaohuang Weng3,4, Guangxian Zhong3,4, Jingfeng Liu6, Xinhua Lin3,4, Jian-hua Lin7, Xuhai Chen81Department of Laboratory Medicine, Fujian Medical University, Fuzhou, 2Department of Gene Diagnosis, Fujian Medical University, Fuzhou, 3Department of Nano-Biomedical Research Center, Fujian Medical University, Fuzhou, 4Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, 5Department of Pathology, Fujian Medical University, Fuzhou, 6Department of Surgery, Fujian Medical University, Fuzhou, 7Department of Bone Oncology, First Affiliated Hospital, Fujian Medical University, Fuzhou, 8College of Electrical Engineering and Automation, Fuzhou University, Fuzhou, People's Republic of ChinaObjective: To review the feasibility of coupling the techniques of random amplified polymorphic DNA (RAPD with carbon nanotube-based modified electrode for guanine/deoxy-guanine triphosphate (dGTP electrochemical sensing for mapping of the pancreatic cancer genetic fingerprint and screening of genetic alterations.Methods: We developed a new method to study the electrochemical behavior of dGTP utilizing carbon multiwalled nanotube (MWNT-modified glassy carbon electrodes (GCEs. RAPD was applied for amplification of DNA samples from healthy controls and patients with pancreatic cancer under the same conditions to determine the different surplus quantity of dGTP in the polymerase chain reaction (PCR, thereby determining the difference/quantity of PCR products or template strands. Using this method we generated a genetic fingerprint map of pancreatic cancer through the combination of electrochemical sensors and gel electrophoresis to screen for genetic alterations. Cloning and sequencing were then performed to verify these gene alterations.Results: dGTP showed favorable electrochemical behavior on the MWNTs/GCE. The results indicated that the electrical signal and dGTP had a satisfactory linear relationship with the d
... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...
This review was written rather against Mendelsohn's reductionist model for cancer risk in A-bomb survivors in following chapters. Assumptions for carcinogenic process: mutation of a cell to the cancer cell and its proliferation. Multi-step theory for carcinogenesis and age of crisis: induction of cancer by accumulation of cancer-related gene mutations which being linear to time (age). Effect of exogenous hit in the multi-step theory: radiation as an exogenous hit to damage DNA. Dose-effect relationship for cancer risk in the survivors and the problem for the latent period: for solid tumors, dose-effect relationship is linear and shortening of the latent period is not observed. Considerations on cancer data in adulthood exposure/Indirect effect model in radiation carcinogenesis: solid cancer data supporting the indirect effect model. Possible mechanism for radiation-induced long-term increase of natural mutation frequency: genetic instability remaining in the irradiated cells which being a basis of the indirect effect model. Notes for considerations of carcinogenicity in exposed people/Difference in carcinogenic mechanisms due to age. The author concluded that the radiation-induced carcinogenesis is deeply related with the natural carcinogenesis and particularly for solid cancers, it can not be explained by the classic reductionist model. (K.H.)
［1］Froudarakis ME, Bouros D, Spandidos DA, et al. Microsatellite instability and loss of heterozygosity at chromosomes 17 in non-small cell lung cancer [J]. Chest 1998; 113:1091.［2］Fong KM, Zimmerman PV, Smith PJ. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer [J]. Cancer Res 1994; 54:2098.［3］Mountain CF. A new international staging system for lung cancer [J]. Chest 1986; 89(suppl):225.［4］Shridhar V, Siegfried J, Hunt J, et al. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas [J]. Cancer Res 1994; 54:2084.［5］Loeb LA. Microsatellite instability: Marker of a mutator phenotype in cancer [J]. Cancer Res 1994; 54:5059.［6］Sanchez CM, Monzo M, Rosell R, et al. Detection of chromosome 3p alterations in serum DNA of non-small cell lung cancer patients [J]. Ann Oncol 1989; 113.
Studies on the Japanese atomic-bomb survivors have been providing important knowledge on late effects of ionizing radiation exposure at low/moderate doses. In particular, the long-term follow-up in the Life Span Study (LSS) of survivors has played major roles to characterize the radiation-induced risks of various cancer and non-cancer outcomes. Lung cancer, the most common cancer worldwide and the second most in the LSS, is among those cancers strongly associated with radiation exposure. While numerous studies have linked radon and other types of radiation to lung cancer, questions remain about how smoking interacts with radiation for this predominant cause of death. It has not been clear how such joint effects differ by histological subtype of lung cancer. In addition, molecular mechanisms of the late effects of radiation exposure on lung cancer development are not clear, and thus there is considerable interest in the radiation-associated lung carcinogenesis, which is believed to involve multiple stages with potentially many genetic and epigenetic alterations. In attempts to find answers to these questions, some studies have been conducted with data of atomic-bomb survivors, a couple of which will be introduced in the following. (author)
Domingo, Laia; Jacobsen, Katja Kemp; von Euler-Chelpin, My Catarina;
Background. Long-term data on breast cancer detection in mammography screening programs are warranted to better understand the mechanisms by which screening changes the breast cancer pattern in the population. We aimed to analyze 17 years of breast cancer detection rates inside and outside...... to women aged 50-69 years. We identified targeted, eligible, invited and participating women. We calculated screening detection and interval cancer rates for participants, and breast cancer incidence in non-screened women (= targeted women excluding participants) by biennial invitation rounds. Tumor...... characteristics were tabulated for each of the three groups of cancers. Results. Start of screening resulted in a prevalence peak in participants, followed by a decrease to a fairly stable detection rate in subsequent invitation rounds. A similar pattern was found for breast cancer incidence in non-screened women...
Klepstad, P; Fladvad, T; Skorpen, F;
variability with opioid doses in a large population using a confirmatory validation population was warranted. We recruited 2294 adult European patients using a World Health Organization (WHO) step III opioid and analyzed single nucleotide polymorphisms (SNPs) in genes with a putative influence on opioid...... validating findings obtained in genetic association studies to avoid reporting spurious associations as valid findings. To elicit knowledge about new genes that influence pain and the need for opioids, strategies other than the candidate gene approach is needed....
Jessica A Hill
Full Text Available Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills.The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire.Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions.A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.
Wyrobek, A J; Schmid, T E; Marchetti, F
Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.
Dil'man, V M; Blagosklonnyĭ, M V
It is suggested that the transforming protein (type pp60) induce "insulinization" of the cell membrane. It is mostly due to this effect that the cell sensitivity to insulin and insulin-like factors of the body internal medium is enhanced, which in turn results in the increased glucosa transport into cell. The transforming protein is also supposed to increase the activity of the glycolysis key enzymes by phosphorylating them. The presence of these two effects seems to be sufficient enough to explain "the biochemical behaviour" of the cancerous cell. PMID:7385728
Full Text Available Santanu K Datta1,2, Adam H Buchanan3, Gail P Hollowell4, Henry F Beresford5, Paul K Marcom1,3, Martha B Adams1,61Department of Medicine, Duke University; 2Center for Health Services Research in Primary Care, Durham VA Medical Center; 3Duke Cancer Institute, Duke University; 4Department of Biology, North Carolina Central University; 5School of Nursing, Duke University; 6Department of Community and Family Medicine, Duke University, Durham, NC, USAAbstract: Cancer genetic counseling (CGC provides benefits and is the standard of care for individuals at increased risk of having a hereditary cancer syndrome. CGC services are typically centered in urban medical centers, leading to limited access to counseling in rural communities. Telemedicine has the potential to improve access to CGC, increase efficient use of genetic counselors, and improve patient care in rural communities. For telemedicine CGC to gain wide acceptance and implementation it needs to be shown that individuals who receive telemedicine CGC have high satisfaction levels and that CGC is cost-effective; however little research has been conducted to measure the impact of telemedicine CGC. This paper describes the design and methodology of a randomized controlled trial comparing telemedicine with in-person CGC. Measurement of patient satisfaction and effectiveness outcomes are described, as is measurement of costs that are included in an economic analysis. Study design and methodologies used are presented as a contribution to future comparative effectiveness investigations in the telemedicine genetic counseling field.Keywords: cancer genetics, genetic counseling, rural health services, telemedicine, satisfaction, cost
Campa, Daniele; McKay, James; Sinilnikova, Olga;
FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases....... Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by......Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element...
Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either 'gain' (oncogenes) or 'lose' (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ('epi-mutations') turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms. (authors)
Full Text Available There is growing evidence that inclusion of genetic information about known common susceptibility variants may enable population risk-stratification and personalized prevention for common diseases including cancer. This would require the inclusion of genetic testing as an integral part of individual risk assessment of an asymptomatic individual. Front line health professionals would be expected to interact with and assist asymptomatic individuals through the risk stratification process. In that case, additional knowledge and skills may be needed. Current guidelines and frameworks for genetic competencies of non-specialist health professionals place an emphasis on rare inherited genetic diseases. For common diseases, health professionals do use risk assessment tools but such tools currently do not assess genetic susceptibility of individuals. In this article, we compare the skills and knowledge needed by non-genetic health professionals, if risk-stratified prevention is implemented, with existing competence recommendations from the UK, USA and Europe, in order to assess the gaps in current competences. We found that health professionals would benefit from understanding the contribution of common genetic variations in disease risk, the rationale for a risk-stratified prevention pathway, and the implications of using genomic information in risk-assessment and risk management of asymptomatic individuals for common disease prevention.
Goldim, José Roberto; Gibbon, Sahra
Drawing from perspectives of both bioethics and anthropology, this article explores how the boundaries between personal and relational privacy are negotiated by patients and practitioners in the context of an emerging domain of cancer genetics in Brazil. It reflects on the place of informed consent in the history of bioethics in North America in contrast to the development of bioethics in Brazil and the particular social cultural context in which consent is sought in Brazilian public health care. Making use of empirical research with families and individuals receiving genetic counselling related to increased genetic risk for cancer, in genetic clinics in southern Brazil, it examines how informed consent is linked to the necessary movement between personal and relational privacy. The paper illustrates the value of a particular tool known as a 'sociogram' to examine the complex interpersonal dynamics that arise in negotiating informed consent at the interface between the family and the individual in Brazil. The paper, therefore, points to the scope of further interdisciplinary exchanges between anthropology and bioethics, confronting the new challenges that arise in the context of medical genetics in developing country. PMID:25998783
Alladi, Subha Mahadevi; P, Shinde Santosh; Ravi, Vadlamani; Murthy, Upadhyayula Suryanarayana
Micro array data provides information of expression levels of thousands of genes in a cell in a single experiment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. In our present study we have used the benchmark colon cancer data set for analysis. Feature selection is done using t‐statistic. Comparative study of class prediction accuracy of 3 different classifiers viz., support vector machine (SVM), neural nets and logistic regression was performed using the top 10 genes ranked by the t‐statistic. SVM turned out to be the best classifier for this dataset based on area under the receiver operating characteristic curve (AUC) and total accuracy. Logistic Regression ranks as the next best classifier followed by Multi Layer Perceptron (MLP). The top 10 genes selected by us for classification are all well documented for their variable expression in colon cancer. We conclude that SVM together with t-statistic based feature selection is an efficient and viable alternative to popular techniques. PMID:19238250
... Physician Resources Professions Site Index A-Z Prostate Cancer Treatment Prostate cancer overview? What are my treatment options? What ... any new developments in treating my disease? Prostate cancer overview Prostate cancer is the most common form of cancer ...
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Bignold, Leon P; Coghlan, B L D; Jersmann, H P A
Morphological abnormalities of both the nuclei and the cell bodies of tumour cells were described by Müller in the late 1830s. Abnormalities of mitoses and chromosomes in tumour cells were described in the late 1880s. Von Hansemann, in the 1890s, suggested that tumour cells develop from normal cells because of a tendency to mal-distribution and other changes of chromosomes occurring during mitosis. In the first decades of the 20th century, Mendelian genetics and "gene mapping" of chromosomes were established, and the dominant or recessive bases of the familial predispositions to certain tumour types were recognised. In the same period, the carcinogenic effects of ionising radiations, of certain chemicals and of particular viruses were described. A well-developed "somatic gene-mutational theory" of tumours was postulated by Bauer in 1928. In support of this, in the next three decades, many environmental agents were found to cause mitotic and chromosomal abnormalities in normal cells as well as mutations in germ-line cells of experimental animals. Nevertheless, mitotic, chromosomal, and other mutational theories were not popular explanations of tumour pathogenesis in the first half of the 20th century. Only in the 1960s did somatic mutational mechanisms come to dominate theories of tumour formation, especially as a result of the discoveries of the reactivity of carcinogens with DNA, and that the mutation responsible for xeroderma pigmentosum causes loss of function of a gene involved in the repair of DNA after damage by ultraviolet light (Cleaver in 1968). To explain the complexity of tumourous phenomena, "multi-hit" models gained popularity over "single-hit" models of somatic mutation, and "epigenetic" mechanisms of gene regulation began to be studied in tumour cells. More recently, the documentation of much larger-than-expected numbers of genomic events in tumour cells (by Stoler and co-workers, in 1999) has raised the issue of somatic genetic instability in
Teixeira, José Henrique; Silva, Patrícia Manuela; Reis, Rita Margarida; Moura, Inês Moranguinho; Marques, Sandra; Fonseca, Joana; Monteiro, Luís Silva; Bousbaa, Hassan
Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20. PMID:24995269
Purpose: Local control rates for breast cancer in genetically predisposed women are poorly defined. Because such a small percentage of breast cancer patients have proven germline mutations, surrogates, such as a family history for breast cancer, have been used to examine this issue. The purpose of this study was to evaluate local-regional control following breast conservation therapy (BCT) in patients with bilateral breast cancer and a breast cancer family history. Methods and Materials: We retrospectively reviewed records of all 58 patients with bilateral breast cancer and a breast cancer family history treated in our institution between 1959 and 1998. The primary surgical treatment was a breast-conserving procedure in 55 of the 116 breast cancer cases and a mastectomy in 61. The median follow-up was 68 months for the BCT patients and 57 months for the mastectomy-treated patients. Results: Eight local-regional recurrences occurred in the 55 cases treated with BCT, resulting in 5- and 10-year actuarial local-regional control rates of 86% and 76%, respectively. In the nine cases that did not receive radiation as a component of their BCT, four developed local-regional recurrences (5- and 10-year local-regional control rates of BCT without radiation: 49% and 49%). The 5- and 10-year actuarial local-regional control rates for the 46 cases treated with BCT and radiation were 94% and 83%, respectively. In these cases, there were two late local recurrences, developing at 8 years and 9 years, respectively. A log rank comparison of radiation versus no radiation actuarial data was significant at p = 0.009. In the cases treated with BCT, a multivariate analysis of radiation use, patient age, degree of family history, margin status, and stage revealed that only the use of radiation was associated with improved local control (Cox regression analysis p = 0.021). The 10-year actuarial rates of local-regional control following mastectomy with and without radiation were 91% and 89
Full Text Available Squamous cell carcinoma of the cervix (SCCC is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV is the major risk factor to develop malignant lesions in the cervix. Polymorphisms of the MHC and p53 genes seem to influence the outcome of HPV infection and progression to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53 and mediates its degradation by the ubiquitin pathway. The role of these polymorphisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.
Radiation induced breast cancer: Influence of age at exposure, time since exposure, attained age and genetic predisposition. The amount of undesirable effects of screening with mammography was estimated from mortality studies after radiation exposure. Newer incidence studies demonstrate, however, an underestimation of the health detriment by mortality studies, in particular with increasing age at exposure, which amounts about five- to sixfold after an exposure in an age of 45-50y. The multidimensional analysis of the discrete values of incidence after radiation exposure respecting age at exposure, time since exposure and attained age instead of calculating a steady function simply depending from age at exposure results in an increasing relative and absolute risk of cancer incidence (and mortality) with growing age after an exposure at an age above 40y. Some genes seems to be correlated with an predisposition of breast cancer. In women carrying BRCA-1 the radiosensitivity for induction of breast cancer may exceed the risk in the normal population by about two orders of magnitude. The resulting doubling dose amounts in the order of the natural and medical radiation exposure. At least in part the genetic predisposition is associated with an early onset of the cancer after an additional radiation exposure. This kind of health detriment was not considered in the former discussion of radiation hazards. (orig.)
Datta SK; Buchanan AH; Hollowell GP; Beresford HF; Marcom PK; Adams MB
Santanu K Datta1,2, Adam H Buchanan3, Gail P Hollowell4, Henry F Beresford5, Paul K Marcom1,3, Martha B Adams1,61Department of Medicine, Duke University; 2Center for Health Services Research in Primary Care, Durham VA Medical Center; 3Duke Cancer Institute, Duke University; 4Department of Biology, North Carolina Central University; 5School of Nursing, Duke University; 6Department of Community and Family Medicine, Duke University, Durham, NC, USAAbstract: Cancer genetic counseling (CGC) provid...
Garcia, Patty B.; Attardi, Laura D.
The key role of the p53 protein in tumor suppression is highlighted by its frequent mutation in human cancers and by the completely penetrant cancer predisposition of p53 null mice. Beyond providing definitive evidence for the critical function of p53 in tumor suppression, genetically engineered mouse models have offered numerous additional insights into p53 function. p53 knock-in mice expressing tumor-derived p53 mutants have revealed that these mutants display gain-of-function activities th...
A review of recent literature on carcinogenic effects of chemical products derived from the combustion of organic fuels suggests that the numbers of fatal cancers and genetic defects induced by utilization of fossil fuels may be much greater than the numbers induced by utilization of nuclear power to produce the same amount of energy. Despite the uncertainties involved in these estimates, the maximum risk of fatal cancers due to carcinogenic by-products associated with the production of electricity by any of these methods appears to be remarkably low compared with the risk of other fatal hazards in Canada and the U.S.A. (author)
Cancer stem cell model hypothesizes existence of a small proportion of tumor cells capable of sustaining tumor formation, self-renewal and differentiation. In breast cancer, these cells were found to be associated with CD44+CD24-low and ALDH+ phenotype. Our study was performed to evaluate the suitability of current approaches for breast cancer stem cell analyses to evaluate heterogeneity of breast cancer cells through their extensive genetic and epigenetic characterization. Breast cancer cell lines MCF7 and SUM159 were cultured in adherent conditions and as mammospheres. Flow cytometry sorting for CD44, CD24 and ALDH was performed. Sorted and unsorted populations, mammospheres and adherent cell cultures were subjected to DNA profiling by array CGH and methylation profiling by Epitect Methyl qPCR array. Methylation status of selected genes was further evaluated by pyrosequencing. Functional impact of methylation was evaluated by mRNA analysis for selected genes. Array CGH did not reveal any genomic differences. In contrast, putative breast cancer stem cells showed altered methylation levels of several genes compared to parental tumor cells. Our results underpin the hypothesis that epigenetic mechanisms seem to play a major role in the regulation of CSCs. However, it is also clear that more efficient methods for CSC enrichment are needed. This work underscores requirement of additional approaches to reveal heterogeneity within breast cancer
AL-QASEM, ABEER J.; TOULIMAT, MOHAMED; ELDALI, ABDELMONEIM M.; TULBAH, ASMA; AL-YOUSEF, NUJOUD; AL-DAIHAN, SOOAD K.; AL-TASSAN, NADA; AL-TWEIGERI, TAHER; ABOUSSEKHRA, ABDELILAH
Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4–9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals. PMID:22866089
Al-Qasem, Abeer J; Toulimat, Mohamed; Eldali, Abdelmoneim M; Tulbah, Asma; Al-Yousef, Nujoud; Al-Daihan, Sooad K; Al-Tassan, Nada; Al-Tweigeri, Taher; Aboussekhra, Abdelilah
Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals. PMID:22866089
Full Text Available ... Overview Cancer Screening Overview–for health professionals Screening Tests Research Diagnosis and Staging Symptoms Diagnosis Staging Prognosis ... Cancer Prevention Overview Screening Cancer Screening Overview Screening Tests Diagnosis & Staging Symptoms Diagnosis Staging Prognosis Treatment Types ...
Cohen, Stephanie A; McIlvried, Dawn E
Cancer genetic counseling sessions traditionally encompass collecting medical and family history information, evaluating that information for the likelihood of a genetic predisposition for a hereditary cancer syndrome, conveying that information to the patient, offering genetic testing when appropriate, obtaining consent and subsequently documenting the encounter with a clinic note and pedigree. Software programs exist to collect family and medical history information electronically, intending to improve efficiency and simplicity of collecting, managing and storing this data. This study compares the genetic counselor's time spent in cancer genetic counseling tasks in a traditional model and one using computer-assisted data collection, which is then used to generate a pedigree, risk assessment and consult note. Genetic counselor time spent collecting family and medical history and providing face-to-face counseling for a new patient session decreased from an average of 85-69 min when using the computer-assisted data collection. However, there was no statistically significant change in overall genetic counselor time on all aspects of the genetic counseling process, due to an increased amount of time spent generating an electronic pedigree and consult note. Improvements in the computer program's technical design would potentially minimize data manipulation. Certain aspects of this program, such as electronic collection of family history and risk assessment, appear effective in improving cancer genetic counseling efficiency while others, such as generating an electronic pedigree and consult note, do not. PMID:21240560
Andersen, Vibeke; Vogel, Ulla
Meat intake is associated with the risk of colorectal cancer. The objective of this systematic review was to evaluate interactions between meat intake and genetic variation in order to identify biological pathways involved in meat carcinogenesis. We performed a literature search of PubMed and...... Embase using "interaction", "meat", "polymorphisms", and "colorectal cancer", and data on meat-gene interactions were extracted. The studies were divided according to whether information on meat intake was collected prospectively or retrospectively. In prospective studies, interactions between meat...... polymorphism in XPC and meat was found in one prospective and one case-control study; however, the directions of the risk estimates were opposite. Thus, none of the findings were replicated. The results from this systematic review suggest that genetic variation in the inflammatory response and DNA repair...
Song, H.; Hogdall, E.; Ramus, S.J.;
PURPOSE: Somatic alterations have been shown to correlate with ovarian cancer prognosis and survival, but less is known about the effects on survival of common inherited genetic variation. Of particular interest are genes involved in cell cycle pathways, which regulate cell division and could...... plausibly influence clinical characteristics of multiple tumors types. EXPERIMENTAL DESIGN: We examined associations between common germ-line genetic variation in 14 genes involved in cell cycle pathway (CCND1, CCND2, CCND3, CCNE1, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CDK2, CDK4, CDK6, and RB1......) and survival among women with invasive ovarian cancer participating in a multicenter case-control study from United Kingdom, Denmark, and United States. DNAs from up to 1,499 women were genotyped for 97 single-nucleotide polymorphisms that tagged the known common variants (minor allele frequency > or = 0...
Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G
Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials. PMID:26306257
Full Text Available The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (± 10 kb in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥ 7 revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the P(trend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r(2 ≥ 0.98. Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.
Full Text Available Abstract This is a short summary of a meeting of the "African-Caribbean Cancer Consortium", jointly organized by the University of Pittsburgh, Department of Epidemiology and the University of Pittsburgh Cancer Institute, held in Montego Bay, Jamaica as a satellite meeting at the Caribbean Health Research Council, 52nd Annual Council and Scientific meeting on May 4, 2007.
Barratt, Daniel T; Bandak, Benedikte; Klepstad, Pål;
This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl....
Kash, K M
In summary, we need to provide fully informed consent regarding the hazards and the benefits of genetic testing and defining risk. This reflects the first ethical principle of autonomy. It is the responsibility of the counseling team to make sure that the individual is psychologically equipped to deal with the emotional distress that may result from testing. An undue burden must not be placed on someone and harm must not be inflicted. This is the second ethical principle of beneficence. Third, awareness of the potential problems of testing is extremely important. These issues are those of disclosure, insurance problems, and employment problems--the third ethical principle of confidentiality. Recommendations for screening guidelines, regardless of testing results, should be provided. It is important for women who are not gene carriers to know that they still need to go for screening. Lastly, we need to find ways to help individuals cope with their risk status, whether it is actual high risk or perceived high risk. Helping women to develop positive coping strategies and to adhere to screening is extremely important. As the Huntington's data indicated, over time, regardless of their risk levels, individuals do learn how to cope and adapt with the outcome of testing. Women and men need to learn how to live with their risk status so that the negative psychological sequelae will be minimized. PMID:8526383
Goldim, J. R.; Gibbon, S.
Drawing from perspectives of both bioethics and anthropology, this article explores how the boundaries between personal and relational privacy are negotiated by patients and practitioners in the context of an emerging domain of cancer genetics in Brazil. It reflects on the place of informed consent in the history of bioethics in North America in contrast to the development of bioethics in Brazil and the particular social cultural context in which consent is sought in Brazilian public health c...
Andersen, Vibeke; Vogel, Ulla
Meat intake is associated with the risk of colorectal cancer. The objective of this systematic review was to evaluate interactions between meat intake and genetic variation in order to identify biological pathways involved in meat carcinogenesis. We performed a literature search of PubMed and Embase using “interaction”, “meat”, “polymorphisms”, and “colorectal cancer”, and data on meat–gene interactions were extracted. The studies were divided according to whether information on meat intake w...
Pieterse, A H; Dulmen, S. van; van Dijk, Sandra; Bensing, J.; Ausems, M.G.E.M.
Purpose: There is no consensus on how best to communicate risk in breast cancer genetic counseling. We studied risk communication in completed series of counseling visits and assessed associations with counselees' postcounseling risk perception and satisfaction. Methods: Pre- and postcounseling questionnaires and videorecordings of all visits were available for 51 affected and unaffected women from families with no known BRCA1/2 mutation, who fulfilled criteria for DNA testing. We developed a...
Pardini, Barbara; Naccarati, Alessio; Novotný, J.; Šmerhovský, Z.; Vodičková, Ludmila; Poláková, Veronika; Hánová, Monika; Slyšková, Jana; Tulupová, Elena; Kumar, R.; Bortlík, M.; Barale, R.; Hemminki, K.; Vodička, Pavel
Roč. 638, 1-2 (2008), s. 146-153. ISSN 0027-5107 R&D Projects: GA ČR GA310/05/2626; GA MZd NR8563 Grant ostatní: EU(SE) 505609 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK Keywords : Colorectal cancer * Individual susceptibility * DNA repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008
Current therapeutic approaches against the advanced stages of human solid tumors are palliative rather than curative. Many modalities, including, surgery, radiation, and chemotherapy, either alone or in combination have met with only modest success for advanced metastatic cancers. Radioimmunotherapy (RIT) combines the specificity of monoclonal antibodies with cytotoxic effects of radioisotopes. It is the ''smart'' way of delivering radiation to the known and occult metastatic cancer cells and is independent of drug toxicity and/or hormone resistance. The tumor associated glycoprotein-72 (TAG-72) containing the unique disaccharide sialyl-Tn, is highly expressed in majority of adenocarcinomas, including carcinomas of the prostate, breast, ovaries, pancreas and colon (80-90%) compared to undetectable expression in normal tissues. Monoclonal antibody CC49, reactive with TAG-72, after conjugation to potent gamma- and beta-emitting radionuclides, has been useful in selective systemic radiolocalization of disease and therapy of primary and metastatic tumor sites. However, limited therapeutic responses were observed in patients. Limited success of antibody based delivery of radioisotopes can be attributed to several factors including undesirable pharmacokinetics, poor tumor uptake and high immunogenicity of intact antibodies (IgGs). The primary factors contributing towards the failure of RIT include: (1) longer serum half-lives of the intact IgG molecules resulting in the radiotoxicity, (2) generation of human antibodies against murine antibodies (HAMA) that limits the frequency of dose administration, (3) poor diffusion rates of intact IgG due to the large size and (4) high interstitial fluid pressures (IFP) encountered in solid tumors. The major goal of our multidisciplinary project was to develop specific novel radiopharmaceuticals, with desired pharmacokinetics, for the diagnosis and therapy of solid tumors. To overcome the low uptake of radioactivity by tumors and to
Surinder Batra, Ph D
Current therapeutic approaches against the advanced stages of human solid tumors are palliative rather than curative. Many modalities, including, surgery, radiation, and chemotherapy, either alone or in combination have met with only modest success for advanced metastatic cancers. Radioimmunotherapy (RIT) combines the specificity of monoclonal antibodies with cytotxic effects of radioisotopes. It is the smart way of delivering radiation to the known and occult metastatic cancer cells and is independent of drug toxicity and/or hormone resistance. The tumor associated glycoprotein-72 (TAG-72) containing the unique disaccharide sialyl-Tn, is highly expressed in majority of adenocarcinomas, including carcinomas of the prostate, breast, ovaries, pancreas and colon (80-90%) compared to undetectable expression in normal tissues. Monoclonal antibody CC49, reactive with TAG-72, after conjugation to potent gamma- and beta-emitting radionuclides, has been useful in selective systemic radiolocalization of disease and therapy of primary and metastatic tumor sites. However, limited therapeutic responses were observed in patients. Limited success of antibody based delivery of radioisotopes can be attributed to several factors including undesirable pharmacokinetics, poor tumor uptake and high immunogenicity of intact antibodies (IgGs). The primary factors contributing towards the failure of RIT include: 1) longer serum half-lives of the intact IgG molecules resulting in the radiotoxicity, 2) generation of human antibodies against murine antibodies (HAMA) that limits the frequency of dose administration, 3) poor diffusion rates of intact IgG due to the large size and 4) high interstitial fluid pressures (IFP) encountered in solid tumors. The major goal of our multidisciplinary project was to develop specific novel radiopharmaceuticals, with desired pharmacokinetics, for the diagnosis and therapy of solid tumors. To overcome the low uptake of radioactivity by tumors and to increase
Chikako Kiyohara, Kouichi Yoshimasu
Full Text Available Various DNA alterations can be caused by exposure to environmental and endogenous carcinogens. Most of these alterations, if not repaired, can result in genetic instability, mutagenesis and cell death. DNA repair mechanisms are important for maintaining DNA integrity and preventing carcinogenesis. Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide excision repair pathway genes, focusing on xeroderma pigmentosum group A (XPA, excision repair cross complementing group 1 (ERCC1, ERCC2/XPD, ERCC4/XPF and ERCC5/XPG. We found an increased risk of lung cancer among subjects carrying the ERCC2 751Gln/Gln genotype (odds ratio (OR = 1.30, 95% confidence interval (CI = 1.14 - 1.49. We found a protective effect of the XPA 23G/G genotype (OR = 0.75, 95% CI = 0.59 - 0.95. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples.
Hagay Sobol; Yves-Jean Bignon; Catherine Bonaiti; Jean Cuisenier; Christine Lasset; Alain Lortholary; Catherine Noguès; Dominique Stoppa-Lyonnet; François Eisinger; The French Cooperative Network/Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer
AIM: In order to evaluate the characteristics and the evolution of cancer genetics activity in France, a survey was conducted at the national level during a period of 4 years from 1994 to 1997 through the French Cooperative Network, a multidisciplinary group formed to investigate inherited tumors. METHOD: A questionnaire was sent to all the 29 French non-specialized cancer genetic clinics to evaluate activity during a period of 4 consecutive weeks each year from 1994 to 1997. Items concerning...
Mattina, Gabriella Francesca; Steiner, Meir
Obsessive-compulsive disorder (OCD) is a heterogeneous mental disorder that significantly impairs an individual's functioning. The candidate gene approach has proven to be a useful tool in investigating potential risk genes for OCD, but genetic studies have been largely inconclusive. Etiologically distinct forms of obsessive-compulsive disorder based on sex and age of onset have been identified, yet many genetic studies fail to examine the association by these subtypes. Due to the sexually dimorphic nature of the disorder, positive associations have been found with OCD in males only, suggesting the potential for identifying risk genes that contribute to OCD in women, such as perinatal OCD. This review includes a brief overview of the disorder and its subtypes, with a current update on candidate genes that may contribute to OCD using single nucleotide polymorphisms (SNPs) and genome wide association studies (GWAS). PMID:26827635
This chapter provides an overview of the techniques, current status and issues involved in using marker-assisted selection (MAS) for genetic improvement in developing countries. Molecular marker maps, the necessary framework for any MAS programme, have been constructed for the majority of agriculturally important species, although the density of the maps varies considerably among species. Despite the considerable resources that have been invested in this field and despite the enormous potential it still represents, with few exceptions, MAS has not yet delivered its expected benefits in commercial breeding programmes for crops, livestock, forest trees or farmed fish in the developed world. When evaluating the potential merits of applying MAS as a tool for genetic improvement in developing countries, some of the issues that should be considered are its economic costs and benefits, its potential benefits compared with conventional breeding or with application of other biotechnologies, and the potential impact of intellectual property rights (IPRs) on the development and application of MAS. (author)
Full Text Available Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium, fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids, which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.
Kjaergaard, Alisa D; Nordestgaard, Børge G; Johansen, Julia S;
Plasma YKL-40 is high in patients with cancer and in individuals who later develop cancer. Whether YKL-40 is only a marker or indeed a cause of cancer is presently unknown. We tested the hypothesis that observationally and genetically, high plasma YKL-40 is associated with high risk of cancer. For...... cancer, 913 developed lung cancer, 2,863 women developed breast cancer, 1,557 men developed prostate cancer and 5,146 individuals developed other cancer. Follow-up was 100% complete. Multifactorially and CRP adjusted hazard ratio (HR) for gastrointestinal cancer was 1.82 (95%CI, 1.16-2.86) for 96......-100% versus 0-33% YKL-40 percentile category. Corresponding HR were 1.71 (0.95-3.07) for lung cancer, but insignificant for breast cancer, prostate cancer and other cancers. CHI3L1 rs4950928 genotype was associated with plasmaYKL-40 levels, but not with risk of any cancer category. For gastrointestinal cancer...
O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica M J; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B
Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. PMID:26330482
Martha L Slattery
Full Text Available BACKGROUND: Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. METHODS: We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls and rectal (n = 754 cases, 959 controls cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH, SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. RESULTS: After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208. Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300. Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR and rectal cancer (SepX1 increased HRR. CONCLUSIONS: Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is
Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S
During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...
Landau-Ossondo, M; Rabia, N; Jos-Pelage, J; Marquet, L M; Isidore, Y; Saint-Aimé, C; Martin, M; Irigaray, P; Belpomme, D
Prostate and breast cancers have become very frequent in Martinique. We previously conducted a multifactorial analysis in the French Caribbean Island, Martinique, in order to elucidate the aetiology of prostate cancer. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. Although a Caribbean genetic susceptibility factor may be involved in prostate carcinogenesis: this factor, because it could not have changed during the observation period, cannot per se account for the growing incidence of this cancer in the island. We therefore suggested that among possible environmental factors, the intensive and prolonged exposure to Carcinogenic, Mutagenic and/or Reprotoxic (CMR) or presumed CMR pesticides may account for the observed growing incidence of prostate cancer and thus may be involved in prostate carcinogenesis. In this study, we further attempt to show that due to their carcinogenic properties, pesticides and especially organochlorine pesticides may in fact be causally implicated in the growing incidence of prostate cancer in Martinique. Also, we suggest that CMR or presumed CMR pesticides may be causally involved in the growing incidence of breast cancer through a common endocrine disruption mechanism. We therefore propose that protective medical recommendations should be immediately set up and carried out by general practitioners, paediatricians, obstetricians, gynaecologists and urologists; and that public health measures of primary precaution and prevention should be urgently taken in close collaboration with health professionals in order to protect population, more especially pregnant women and children, with the final objective perhaps that these medical recommendations and public health measures will stop Martinique's cancer epidemic. PMID:19570649
Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua
Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy. PMID:26923776
... was previously published in the Federal Register on March 15, 2011 (76 FR 14034) and allowed 60-days... Genetics Services Directory Web-Based Application Form and Update Mailer Summary: Under the provisions of... Collection: Title: NCI Cancer Genetics Services Directory Web-based Application Form and Update Mailer....
Paige M Bracci
In the U.S. pancreatic cancer is characterized by a low 5-year survival rate of approximately 6%, fewer than 10% of patients diagnosed with localized disease and thus candidates for “curative” surgical resection, increasing incidence and few established risk factors. Similar statistics are observed for other industrialized nations. With new evidence to suggest that pancreatic cancer develops over a number of years, markers that can better identify high risk patients and are applicable to earl...
Orestis Argyros; Suet Ping Wong; Kate Gowers; Richard Paul Harbottle
The development of genetically marked animal tumour xenografts is an area of ongoing research to enable easier and more reliable testing of cancer therapies. Genetically marked tumour models have a number of advantages over conventional tumour models, including the easy longitudinal monitoring of therapies and the reduced number of animals needed for trials. Several different methods have been used in previous studies to mark tumours genetically, however all have limitations, such as genotoxi...
Landsbergen, Karin M.; Prins, Judith B; Brunner, Han G.; Kraaimaat, Floris W.; Hoogerbrugge, Nicoline
An increasing number of patients with colorectal cancer (CRC) receive genetic counselling within 1 year after diagnosis. Little is known whether specific subgroups are more vulnerable for genetic testing related distress. A literature review was conducted to identify the psychological impact of CRC in the first year, and the additional impact of genetic testing. The electronic databases of PubMed, PsychInfo, Embase and the Cochrane Library were searched to identify all reports published betwe...
Suda, Kenichi; Tomizawa, Kenji; Mizuuchi, Hiroshi; Ito, Simon; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Yoshida, Tsukihisa; Okamoto, Tatsuro; Maehara, Yoshihiko; Yatabe, Yasushi; Mitsudomi, Tetsuya
Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged ≥75 years with those of patients aged ≤ 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis, we retrospectively analyzed 405 surgically treated non-small cell lung cancers (NSCLCs) before the era of routine clinical application of post-surgical adjuvant chemotherapy. Postsurgical recurrence-free survival (RFS) was compared between elderly patients and younger counterparts. The genetic analysis showed elderly non-squamous cell lung cancer patients to have higher prevalence of EGFR mutations (53.1 % vs 42.0%, P = 0.15) and lower prevalence of the ALK translocation (0 % vs 4.5%, P = 0.23) than their younger counterparts. The prognostic analysis showed postsurgical RFS was similar between the elderly NSCLC patients and the younger patients. However in multivariate analysis, adjusting for gender, smoking status, pathological stage, and histology, elderly patients had significantly worse prognoses (HR 1.57, 95% CI, 1.08-2.29; P = 0.02) compared with younger patients. These results suggest differences in genetic and prognostic aspects between elderly lung cancer patients and younger lung cancer patients. PMID:23251849
Lin Cai; Shun-Zhang Yu; Zuo-Feng Zhang
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitroscoamines and Iow molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2Elpolymorphisms are associated with risk s of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including dsmographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes: heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group(6.6%),whereas there was only one in the control group (1.1%).However, there was no statistically significan difference between the two groups (two-tailed Fisher′s exact test, P =0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2(OR = 7.34) than indivduals in control group (X2 = 4.597, for trend P=0.032). The frequencies of genofypes with the C2allele ( C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele ( C1/C1 genotype )among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION
Brierley, Karina L; Bonadies, Danielle C; Moyer, Anne; Matloff, Ellen T
Cancer genetic testing is surrounded by myriad ethical, legal, and psychosocial implications which are being revisited as testing expands into an everyday practice and into more complicated areas like whole exome and direct-to-consumer testing. We chose to survey cancer genetic counselors and physicians from a wide range of non-genetics specialties to determine what they would do if faced with the complex decisions associated with cancer genetic testing, how their views compare, and how they align with current guidelines and data. Genetic counselors were significantly more likely than non-genetics physicians to bill their insurance for testing (94.9 vs. 86.8 %; p = 0.001) and purchase life insurance before testing (86.6 vs. 68.6 %; p = 0.000) and were less likely to use an alias (3.2 vs. 13.2 %; p = 0.000) or order testing on their own DNA (15.3 vs. 24.2 %; p = 0.004). They were also less likely to test their minor children (0.9 vs. 33.1 %; p = 0.000) or test their children without their knowledge and consent/assent (1.4 vs.11.5 %; p = 0.000). The results of our study indicate that there is wide variation regarding what clinicians predict they would do in the areas of ethical, legal and psychosocial issues in cancer genetic testing. Cancer genetic counselors' choices are more aligned with professional guidelines, likely due to their experience in the field and awareness of current guidelines. These data are a starting point for a broader discussion of who should offer cancer genetic counseling and testing to patients, particularly as the complexity of the available testing options and associated issues increase with whole exome sequencing. PMID:24804937
Jessica R Lakritz; Poutahidis, Theofilos; Levkovich, Tatiana; Varian, Bernard J.; Ibrahim, Yassin M.; Chatzigiagkos, Antonis; Mirabal, Sheyla; Eric J Alm; Erdman, Susan E
Recent studies suggest health benefits including protection from cancer after eating fermented foods such as probiotic yogurt, though the mechanisms are not well understood. Here we tested mechanistic hypotheses using two different animal models: the first model studied development of mammary cancer when eating a Westernized diet, and the second studied animals with a genetic predilection to breast cancer. For the first model, outbred Swiss mice were fed a Westernized chow putting them at inc...
Pieterse, A H; Ausems, M.G.E.M.; Spreeuwenberg, P.; Dulmen, S. van
Objective: To evaluate outcomes of breast cancer genetic counseling in women with and without breast cancer. Methods: Seventy-seven first-time attendees (n = 44 affected) completed questionnaires assessing cognitions (risk accuracy, knowledge, perceived personal control [PPC]) and distress (state anxiety [STAI], cancer-related stress reactions [IES]) from immediately before to immediately and six months after completing counseling. Data were analyzed using multilevel repeated measures and tre...
Ahmed, M.; Dorling, L.; Kerns, S.; Fachal, L; Elliott, R.; Partliament, M.; Rosenstein, B S; Vega, A; Gómez-Caamaño, A.; Barnett, G.; Dearnaley, D. P.; Hall, E.; Sydes, M; Burnet, N.; Pharoah, P. D.
BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studie...
Kohaar, Indu; Porter-Gill, Patricia; Lenz, Petra; Fu, Yi-Ping; Mumy, Adam; Tang, Wei; Apolo, Andrea B.; Rothman, Nathaniel; Baris, Dalsu; Schned, Alan R.; Ylaya, Kris; Schwenn, Molly; Johnson, Alison; Jones, Michael; Kida, Masatoshi
A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multi...
Kim, Wook; Yoo, Tag-Keun; Shin, Dong-Jik; Rho, Hyun-Wook; Jin, Han-Jun; Kim, Eun-Tak; Bae, Yoon-Sun
Mitochondrial DNA (mtDNA) variation has recently been suggested to have an association with various cancers, including prostate cancer risk, in human populations. Since mtDNA is haploid and lacks recombination, specific mutations in the mtDNA genome associated with human diseases arise and remain in particular genetic backgrounds referred to as haplogroups. To assess the possible contribution of mtDNA haplogroup-specific mutations to the occurrence of prostate cancer, we have therefore perfor...
A possible link between presumed or measured household radon exposure and lung cancer is reviewed on the basis of published epidemiologic studies. Evidence of a link is reported as a result of studies in Sweden; findings are inconsistent elsewhere. A number of methodological problems were found. Many of the studies are ecological in design and are, therefore, primarily hypothesis generating. A number of studies lack any data on the number of lung cancers and are, therefore, difficult to evaluate. Some other studies provide results that are internally inconsistent. Of the case/control studies, there are many with minimal or no information on active and passive smoking, occupation, family history of cancer, and diet. The case/control studies are generally small in size and of low statistical power. Exposure classifications are nonstandardized, inconsistent in their findings, and often gross in their characterization of radon concentrations. Relatively few of the studies actually measured radon exposure. Some of the studies showed significant positive associations either with geological characteristics, water supply contamination, or house type. No significant associations were found with residence near uranium or radium processing waste. Where radon levels were measured, a relatively small percentage of studies found a statistically significant positive association with lung cancer. Overall, the evidence for an association between residential radon exposure and lung cancer is weak. There is a need for a more decisive case/control epidemiologic study of this problem.55 references
Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M
Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs. PMID:27189371
Martínez-González, Teresa de Jesús; Prada-Morales, Sara; Díaz-Espinos, María Isabel; Bouza-Nebrera, Irene; Lázaro-Escobar, Verónica; Serrano-Gallardo, Pilar
This article is to describe the epidemiological situation of cancer and prevention strategies, particularly related to the work of nurses (primary prevention and early detection), focusing primarily on lung cancer (LC), breast (BC) and colorectal (CRC). 98,046 cancer deaths occurred in Spain in 2006, which is the leading cause of death in our country. The main action of prevention for the LC is based on smoking cessation, the main risk factor (relative risk (RR) from 10 to 30) beside radon and asbestos exposures. Basically the prevention for the BC is based on early detection, mammography remains the ultimate test because it reduces mortality, and must be done along period between 50 and 70 years old with a two-year interval. CRC mortality is reduced by 16% due to early detection test based on fecal occult blood (TsOH), but it's necessary to insist on changes in lifestyle (diet and exercise) as primary prevention strategies, and in breast cancer too. One of the most effective ways to reduce the impact of cancer today is the prevention, which is carried out mainly by the nurses. PMID:22558714
Vogelaar, Ingrid P; Ligtenberg, Marjolijn J L; van der Post, Rachel S; de Voer, Richarda M; Kets, C Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I Jolanda M; Netea, Mihai G; Hoogerbrugge, Nicoline
Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk. PMID:26700889
A brief description is given of the cancer mortality data at the Radiation Effects Research Foundation, with the aim of providing some general perspective on the extent of the excess cancer mortality, for those who may not be inclined to glean this information from the more comprehensive reports on the Life Span Study. In addition, a summary is given of the changes in dosimetry given by the recently installed DS86 system. Even a cursory view of these changes requires consideration of several factors; changes in air doses, in environmental and organ shielding factors, in the extent of the neutron component, and in effects of truncation of exposures at 6 Gy. Finally, a brief discussion is given of the evolution of radiogenic cancer risk estimates during the past 10-15 years. (author)
Lomax Antony J
Full Text Available Abstract Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered.
Lung cancer (LC) still represents one of the most common tumours in both women and men. PET/CT is a whole-body non-invasive imaging procedure that has been increasingly used for the assessment of LC patients. In particular, PET/CT added value to CT is mainly related to a more accurate staging of nodal and metastatic sites and to the evaluation of the response to therapy. Although the most common PET tracer for LC evaluation is 18F-FDG, new tracers have been proposed for the evaluation of lung neuroendocrine tumours (68Ga-DOTA-peptides, 18F-DOPA) and for the assessment of central nervous system metastasis (11C-methionine). This review focuses on the main clinical applications and accuracy of PET/CT for the detection of non-small cells lung cancer (NSCLC), broncho-alveolar carcinoma (BAC), small cells lung cancer (SCLC), lung neuroendocrine tumours (NET) and solitary pulmonary nodules (SPN).
Rapamycin and its derivatives (rapalogs),a group of allosteric inhibitors of mammalian target of rapamycin (mTOR),have been actively tested in a variety of cancer clinical trials,and some have been approved by the Food and Drug Administration for the treatment of certain types of cancers.However,the single agent activity of these compounds in many tumor types remains modest.The mTOR axis is regulated by multiple upstream signaling pathways.Because the genes (e.g.,PIK3CA,KRAS,PTEN,and LKB1) that encode key components in these signaling pathways are frequently mutated in human cancers,a subset of cancer types may be addicted to a given mutation,leading to hyperactivation of the mTOR axis.Thus,efforts have been made to demonstrate the potential impact of genetic alterations on rapalogbased or mTOR-targeted cancer therapy.This review will primarily summarize research advances in this direction.
Full Text Available Prostate cancer (PCa is the second most common cancer in men worldwide. However the etiology of this disease remains largely unclear. Both genetic and environmental factors seem to be involved in the pathogenesis. In the last years the role of reactive oxygen species (ROS in deterioration of DNA, proteins, lipids of membrane cells has been demonstrated. Also external antioxidant factors such as vitamin C and vitamin E, melatonin, that intercept free radicals, play a role, preventing damage to cellular biomolecules. The antioxidant enzyme glutathione peroxidase 1 (GPX1 is a part of the enzymatic antioxidant defence, preventing oxidative damage to DNA, proteins and lipids by detoxifying hydrogen and lipid peroxides that may contribute to prostate cancer development. Some recent studies indicate an association between GPX1 Pro198Leu polymorphism and an increased risk of cancer. So the alimentary integration with an antioxidant agent such as ascorbate of potassium with ribose (PAR can play an important rule in the prevention and also cure of prostatic cancer, opposing the effect of ROS, both in men carriers of the polymorphism the GPX1 Pro198Leu and in the general population after the demonstration on blood samples of an increase of the oxidative stress parameters.
Williams, Heinric; Powell, Isaac J
Prostate cancer is the most common cancer affecting men in the Western world. In the United States, it is the second leading cause of cancer related deaths after lung and bronchus carcinoma. No definitive causes of prostate cancer (PCa) have been identified to date but, increasing age, a positive family history, and sub-Saharan African ancestry are strongly linked to its development. African American men (AAM) have the highest reported incidence rates in the United States and their mortality from the disease is markedly higher than that of European American men (EAM). Conversely, Asian American men and Pacific Islanders (API), American Indian and Alaskan Native (AI/AN) men, and Hispanic men all have lower incidence and mortality rates as compared with EAM. The reasons for these differences are unclear. However, it is clear that AAM have more advanced PCa when diagnosed. Several other reasons have been suggested and these include differences in treatments and health seeking behavior among the ethnic groups, cultural beliefs, environmental/lifestyle factors, dietary and genetic factors. In conclusion, there are multiple factors that impact prostate cancer outcome and that may be responsible for ethnic disparity. These factors are discussed in this chapter. PMID:19107447
... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Screening ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...
Benjamin H. L. Tan; James A. Ross; Stein Kaasa; Frank Skorpen; Kenneth C. H. Fearon; European Palliative Care Research Collaborative
Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986–2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.
Full Text Available Abstract Background Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC. Conclusion This study proposes that variation at putative 8q24 cis-regulator(s of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.
Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are characterized by a high risk and early onset of colorectal cancer (CRC). HNPCC is due to a germline mutation in one of the following MMR genes: MLH1, MSH2, MSH6 and PMS2. A majority of FAP and attenuated FAP (AFAP) cases are due to germline mutations of APC, causing the development of multiple colorectal polyps. To date, over 450 MMR gene mutations and over 800 APC mutations have been identified. Mo...
M. I. Kogan
Full Text Available The early diagnosis and radical treatment of aggressive prostate cancers (PC is an effective way of improving survival and quality of life in patients. To develop mini-invasive tests is one of the ways of solving the problem. The cells of a peripheral blood mononuclear fraction in the expression patterns of their genetic loci reflect the presence or absence of cancers, including information on therapeutic effectiveness. RT-PRC was used to study the relative expression of 15 genetic loci in a chromosome and one locus of mitochondrial DNA in the cells of the peripheral blood mononuclear fraction in patients with PC or benign prostate hyperplasia and in healthy men. The genetic locus patterns whose change may be of informative value for differential diagnosis in patients with different stages of PC were revealed. The authors studied the relationship and showed the prognostic role and non-relationship of the altered transcriptional activity of loci in the TP53, GSTP1, and IL10 genes in PC to the changes in prostate-specific antigen the level with 90 % specificity and 93 % specificity.
Full Text Available To investigate the ability of an automated fluorescent analyzing system to detect microsatellite alterations, in patients with bladder cancer. We investigated 11 with pathology proven bladder Transitional Cell Carcinoma (TCC for microsatellite alterations in blood, urine, and tumor biopsies. DNA was prepared by standard methods from blood, urine and resected tumor specimens, and was used for microsatellite analysis. After the primers were fluorescent labeled, amplification of the DNA was performed with PCR. The PCR products were placed into the automated genetic analyser (ABI Prism 310, Perkin Elmer, USA and were subjected to fluorescent scanning with argon ion laser beams. The fluorescent signal intensity measured by the genetic analyzer measured the product size in terms of base pairs. We found loss of heterozygocity (LOH or microsatellite alterations (a loss or gain of nucleotides, which alter the original normal locus size in all the patients by using fluorescent microsatellite analysis and an automated analyzing system. In each case the genetic changes found in urine samples were identical to those found in the resected tumor sample. The studies demonstrated the ability to detect bladder tumor non-invasively by fluorescent microsatellite analysis of urine samples. Our study supports the worldwide trend for the search of non-invasive methods to detect bladder cancer. We have overcome major obstacles that prevented the clinical use of an experimental system. With our new tested system microsatellite analysis can be done cheaper, faster, easier and with higher scientific accuracy.
Lipkin Steven M
Full Text Available Abstract Background Mouse studies have recently compared the age-onset patterns of cancer between different genotypes. Genes associated with earlier onset are tentatively assigned a causal role in carcinogenesis. These standard analyses ignore the great amount of information about kinetics contained in age-onset curves. We present a method for analyzing kinetics that measures quantitatively the causal role of candidate genes in cancer progression. We use our method to demonstrate a clear association between somatic mutation rates of different DNA mismatch repair (MMR genotypes and the kinetics of cancer progression. Methods Most experimental studies report age-onset curves as the fraction diagnosed with tumors at each age for each group. We use such data to estimate smoothed survival curves, then measure incidence rates at each age by the slope of the fitted curve divided by the fraction of mice that remain undiagnosed for tumors at that age. With the estimated incidence curves, we compare between different genotypes the median age of cancer onset and the acceleration of cancer, which is the rate of increase in incidence with age. Results The direction of change in somatic mutation rate between MMR genotypes predicts the direction of change in the acceleration of cancer onset in all 7 cases (p ˜ 0.008, with the same result for the association between mutation rate and the median age of onset. Conclusion Many animal experiments compare qualitatively the onset curves for different genotypes. If such experiments were designed to analyze kinetics, the research could move to the next stage in which the mechanistic consequences of particular genetic pathways are related to the dynamics of carcinogenesis. The data we analyzed here were not collected to test mechanistic and quantitative hypotheses about kinetics. Even so, a simple reanalysis revealed significant insights about how DNA repair genotypes affect separately the age of onset and the
Mouse studies have recently compared the age-onset patterns of cancer between different genotypes. Genes associated with earlier onset are tentatively assigned a causal role in carcinogenesis. These standard analyses ignore the great amount of information about kinetics contained in age-onset curves. We present a method for analyzing kinetics that measures quantitatively the causal role of candidate genes in cancer progression. We use our method to demonstrate a clear association between somatic mutation rates of different DNA mismatch repair (MMR) genotypes and the kinetics of cancer progression. Most experimental studies report age-onset curves as the fraction diagnosed with tumors at each age for each group. We use such data to estimate smoothed survival curves, then measure incidence rates at each age by the slope of the fitted curve divided by the fraction of mice that remain undiagnosed for tumors at that age. With the estimated incidence curves, we compare between different genotypes the median age of cancer onset and the acceleration of cancer, which is the rate of increase in incidence with age. The direction of change in somatic mutation rate between MMR genotypes predicts the direction of change in the acceleration of cancer onset in all 7 cases (p @@@@ 0.008), with the same result for the association between mutation rate and the median age of onset. Many animal experiments compare qualitatively the onset curves for different genotypes. If such experiments were designed to analyze kinetics, the research could move to the next stage in which the mechanistic consequences of particular genetic pathways are related to the dynamics of carcinogenesis. The data we analyzed here were not collected to test mechanistic and quantitative hypotheses about kinetics. Even so, a simple reanalysis revealed significant insights about how DNA repair genotypes affect separately the age of onset and the acceleration of cancer. Our method of comparing genotypes provides good
Geng, Liguo; Zhu, Meng; Wang, Yuzhuo; Cheng, Yang; Liu, Jia; Shen, Wei; Li, Zhihua; Zhang, Jiahui; Wang, Cheng; Jin, Guangfu; Ma, Hongxia; Shen, Hongbing; Hu, Zhibin; Dai, Juncheng
Chromatin remodeling complexes utilize the energy of ATP hydrolysis to remodel nucleosomes and have essential roles in transcriptional modulation. Increasing evidences indicate that these complexes directly interact with numerous proteins and regulate the formation of cancer. However, few studies reported the association of polymorphisms in chromatin remodeling genes and lung cancer. We hypothesized that variants in critical genes of chromatin remodeling pathway might contribute to the susceptibility of lung cancer. To validate this hypothesis, we systematically screened 40 polymorphisms in six key chromatin remodeling genes (SMARCA5, SMARCC2, SMARCD2, ARID1A, NR3C1 and SATB1) and evaluated them with a case-control study including 1341 cases and 1982 controls. Logistic regression revealed that four variants in NR3C1 and SATB1 were significantly associated with lung cancer risk after false discovery rate (FDR) correction [For NR3C1, rs9324921: odds ratio (OR)=1.23, P for FDR=0.029; rs12521436: OR=0.85, P for FDR=0.040; rs4912913: OR=1.17, P for FDR=0.040; For SATB1, rs6808523: OR=1.33, P for FDR=0.040]. Combing analysis presented a significant allele-dosage tendency for the number of risk alleles and lung cancer risk (Ptrendlung tumor and adjacent normal tissues in the database of The Cancer Genome Atlas (TCGA) (P=0.009 for rs6808523). These findings suggested that genetic variants in key chromatin remodeling genes may contribute to lung cancer risk in Chinese population. Further large and well-designed studies are warranted to validate our results. PMID:27179949
Loud Jennifer T
Full Text Available Abstract Background Complementary and alternative medicine (CAM use is well documented among breast cancer patients and survivors, but little evidence is available to describe rates and patterns of use among women at increased genetic risk of breast cancer. Methods A pre-visit telephone interview was conducted to ascertain CAM use among the BRCA mutation carriers enrolled in a high-risk breast cancer screening study. Participants were asked to report on their use of thirteen therapies within the year prior to enrollment into the study. Logistic regression was used to evaluate the association between various factors and CAM use in this population. Results Among the 164 BRCA1 or BRCA2 mutation-positive (BRCA+ women in this analysis, 78% reported CAM use, with prayer and lifestyle diet being the two most commonly reported modalities. Many subjects used multiple CAM therapies, with 34% reporting use of three or more modalities. The most commonly used modalities were mind-body therapies and biologically-based practices, 61.6% and 51.8%, respectively. High-risk women were more likely to use CAM if they were older, more educated, more worried about ovarian cancer risk, or had a previous cancer diagnosis. Conclusion This study suggests that the prevalence of CAM use is high among BRCA mutation carriers, with frequency of use comparable to that of breast cancer patients and survivors. Given the high prevalence of CAM use in our subjects, especially biologically-based therapies including herbal supplements, whose safety and efficacy in relation to cancer risk are unknown, our study suggests that future research is necessary to clarify these risks, and that it is important for providers to inquire about and to discuss the pros and cons of CAM use with their BRCA+ patients.
Full Text Available The role of somatic mutations in sporadic thyroid cancer is unclear today. Probably they coming out as aetiological factors in carcinogenesis as well as, respectfully to many authors, can to participate in TC pathogenesis and to determine the clinical course and prognosis of the disease. For today as main oncogenes taking part in initiation of thyroid malignant tumors are considered: RET/PTC, TRK, PTEN, P53, RAS, MET, PPARγ. By means of genetic investigations scientists are trying to solve problems with thyroid cancer differentiated diagnostics (cytokeratin-19, cytokeratin-20, mesothelial cells antigen (Hector Battifora MEsotelial (cell or HBME-1, loss of heterozigitoty (LOH in short arm of 3 chromosome (gene VHL -von Hippel Lindau, 3р26. Recently in foreign literature appeared reports of activated mutations in gene BRAF which most frequently are occurred in melanoma and papillary TC. Prognosis of thyroid cancer may reflected by the LOH as a biological breakage as well as changes of tumor suppressive gene P53 which fraught with decrease of disease prognosis. Thus, both researchers and clinicians have many questions concerning the role of genome, particularly in order to precise of genetic abnormality influence on tumor growth and therefore for assessment of clinical prognosis and with aim to chose adequate treatment tactic in each case.
Smyth, Conor; Špakulová, Iva; Cotton-Barratt, Owen; Rafiq, Sajjad; Tapper, William; Upstill-Goddard, Rosanna; Hopper, John L; Makalic, Enes; Schmidt, Daniel F; Kapuscinski, Miroslav; Fliege, Jörg; Collins, Andrew; Brodzki, Jacek; Eccles, Diana M; MacArthur, Ben D
Many common diseases have a complex genetic basis in which large numbers of genetic variations combine with environmental factors to determine risk. However, quantifying such polygenic effects has been challenging. In order to address these difficulties we developed a global measure of the information content of an individual's genome relative to a reference population, which may be used to assess differences in global genome structure between cases and appropriate controls. Informally this measure, which we call relative genome information (RGI), quantifies the relative “disorder” of an individual's genome. In order to test its ability to predict disease risk we used RGI to compare single-nucleotide polymorphism genotypes from two independent samples of women with early-onset breast cancer with three independent sets of controls. We found that RGI was significantly elevated in both sets of breast cancer cases in comparison with all three sets of controls, with disease risk rising sharply with RGI. Furthermore, these differences are not due to associations with common variants at a small number of disease-associated loci, but rather are due to the combined associations of thousands of markers distributed throughout the genome. Our results indicate that the information content of an individual's genome may be used to measure the risk of a complex disease, and suggest that early-onset breast cancer has a strongly polygenic component. PMID:26029704