High Risk Familial Colon Cancer- Genetics And Phenotype View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

1985-2009

FUNDING AMOUNT

2537910 USD

ABSTRACT

DESCRIPTION (provided by applicant): Genetic, clinical and molecular characterization of inherited colon cancer risk is the focus of our present and long-term work. Genes for the rare syndromes of this malignancy have been found but account for only a small fraction of the estimated one-third of colon cancer cases that arise from inheritance. The aims of our present proposal are 1) to identify the susceptibility genes that give rise to the more common inherited risk, 2) to continue to define the associated phenotype, 3) to establish molecular characteristics of the high-risk families and known syndromes with gene expression profiling and 4) to examine the expression of specific APC/beta-catenin pathway genes as potential diagnostic markers. Together these goals will provide tools to identify persons with inherited risk. We will accomplish the aims as follows: We will identify colon cancer susceptibility loci by linkage analysis of large high-risk colon cancer families in which the known syndromes of colon cancer have been ruled out. Colonoscopy is performed on family members to define polyp expression, both for phenotype and linkage analysis. Gene expression profiling by microarray analysis is performed on normal appearing and neoplastic colonic tissue obtained at colonoscopy and immediately preserved. Profiling will assist both in identification of susceptibility pathways and in establishing characteristic expression profiles in the inherited colon cancer settings. Gene expression patterns will be examined in the normal and neoplastic tissue of the high-risk families and compared to similar samples from families with familial adenomatous polyposis (FAP), attenuated FAP, hereditary nonpolyposis colorectal cancer, sporadic adenomatous polyp cases and normal controls. Gene expression will be examined using a reference RNA and analyzed by supervised (and later unsupervised) analysis of the groups. Finally the expression of four specific APC/beta-catenin pathway marker genes will be examined in neoplastic and normal tissues from the above groups by both real-time quantitative PCR and by in situ RNA hybridization. Previous microarray experiments in our laboratory indicate that expression of these genes is frequently perturbed in sporadic polyps, making them attractive markers of cancer susceptibility to evaluate APC/beta-catenin pathway contributions in undefined forms of inherited colon cancer, as compared to defined inherited syndromes. More... »

URL

http://projectreporter.nih.gov/project_info_description.cfm?aid=7214648

Related SciGraph Publications

  • 2017-08. Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah in DIGESTIVE DISEASES AND SCIENCES
  • 2016-12. Familial Risk of Biliary Tract Cancers: A Population-Based Study in Utah in DIGESTIVE DISEASES AND SCIENCES
  • 2015-03. Hereditary and Common Familial Colorectal Cancer: Evidence for Colorectal Screening in DIGESTIVE DISEASES AND SCIENCES
  • 2012-12. The Impact of Family History on the Risk of Colorectal Neoplasia: Don’t Change the Guidelines Just Yet! in DIGESTIVE DISEASES AND SCIENCES
  • 2011-12. Activating mutation in MET oncogene in familial colorectal cancer in BMC CANCER
  • 2011-08. Comparison of compliance for colorectal cancer screening and surveillance by colonoscopy based on risk in GENETICS IN MEDICINE
  • 2011-05. How well does family history predict who will get colorectal cancer? Implications for cancer screening and counseling in GENETICS IN MEDICINE
  • 2010-12. Differential gene expression in primary colonic tissue from control, FAP and AFAP patients reveals unique signatures with diagnostic potential in HEREDITARY CANCER IN CLINICAL PRACTICE
  • 2010-12. Colorectal adenomas and cancer link to chromosome 13q22.1-13q31.3 in a large family with excess colorectal cancer in HEREDITARY CANCER IN CLINICAL PRACTICE
  • 2010-06. Parental Attitudes, Beliefs, and Perceptions about Genetic Testing for FAP and Colorectal Cancer Surveillance in Minors in JOURNAL OF GENETIC COUNSELING
  • 2010-03. Large intron 14 rearrangement in APC results in splice defect and attenuated FAP in HUMAN GENETICS
  • 2010. Attenuated Familial Adenomatous Polyposis: Diagnosis, Management, and Future Prognosis in HEREDITARY COLORECTAL CANCER
  • 2008-12. Design considerations in a sib-pair study of linkage for susceptibility loci in cancer in BMC MEDICAL GENETICS
  • 2008-10. Colonic Adenoma Risk in Familial Colorectal Cancer—A Study of Six Extended Kindreds in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2008-06. Gonadal mosaicism and familial adenomatous polyposis in FAMILIAL CANCER
  • 2007-01. Colorectal Cancer Surveillance Behaviors Among Members of Typical and Attenuated FAP Families in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2006-07. Extracolonic Cancers Associated with Hereditary Nonpolyposis Colorectal Cancer in the Utah Population Database in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2005-09. Frequency of Familial Colon Cancer and Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in a Large Population Database in FAMILIAL CANCER
  • 2005-06. Abdominal desmoid in familial adenomatous polyposis presenting as a pancreatic cystic lesion in FAMILIAL CANCER
  • 2004-10. Phenotypic Characteristics and Risk of Cancer Development in Hyperplastic Polyposis: Case Series and Literature Review in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2004-03. Intron 4 Mutation in APC Gene Results in Splice Defect and Attenuated FAP Phenotype in FAMILIAL CANCER
  • 1994-12. Colorectal cancers of rare histologic types compared with adenocarcinomas in DISEASES OF THE COLON & RECTUM
  • 1991. Genetic Epidemiology of Cancer and Predisposing Lesions in RECENT PROGRESS IN THE GENETIC EPIDEMIOLOGY OF CANCER
  • 1989-02. High prevalence of adenomatous polyps of the duodenal papilla in familial adenomatous polyposis in DIGESTIVE DISEASES AND SCIENCES
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