It is most probable that both genetic and environmental factors contribute to colon cancer etiology. At present, we have the capabilities to look at the interaction between dietary intake and genes which have been linked to colon cancer. In this study, we will obtain tumor tissue from cases enrolled in a large population-based case-control study of colon cancer (CA 48998). DNA will be extracted from tumor tissue and areas of p53 and K-ras genes will be analyzed at known mutational """"""""hot spots,"""""""" to determine the type and location of genetic mutations within the population of colon cancers. We also will evaluate the extent to which microsatellite instability occurs in colon tumors from this population-based study. We will evaluate the associations between these genetic mutations and tumor stage at diagnosis and survival. These data will be linked to environmental data, which includes extensive information on dietary intake within the population, to determine the impact that diet has on causing these somatic mutations (location and type of mutation). Total calories, fat, protein, calcium, fiber, beta carotene, and folic acid will be assessed with these genetic mutations, as will meats (along with method of and degree of cooking), dairy products, legumes, soy products, and fruits and vegetables. Other factors such as physical activity and body size which are closely related to dietary intake will be assessed both for their associations with somatic mutations. It is hypothesized that dietary intake (as specified above), physical inactivity, and a larger body size will contribute to somatic mutations of the p53 and K-ras genes and microsatellite instability. We also will store DNA frpom tumor tissue so that as laboratory techniques for analyzing somatic gene mutations necome refined, the associations between dietary intake and other genes, such as APC and DCC, can be assessed in the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA061757-04
Application #
2700524
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Clifford, Carolyn K
Project Start
1995-08-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Utah
Department
Family Medicine
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Slattery, Martha L; Herrick, Jennifer S; Wolff, Roger K et al. (2017) The miRNA landscape of colorectal polyps. Genes Chromosomes Cancer 56:347-353
Slattery, Martha L; Herrick, Jennifer S; Mullany, Lila E et al. (2016) Colorectal tumor molecular phenotype and miRNA: expression profiles and prognosis. Mod Pathol 29:915-27
Slattery, Martha L; Herrick, Jennifer S; Pellatt, Daniel F et al. (2016) MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression. Carcinogenesis 37:245-261
Khalili, Hamed; Gong, Jian; Brenner, Hermann et al. (2015) Identification of a common variant with potential pleiotropic effect on risk of inflammatory bowel disease and colorectal cancer. Carcinogenesis 36:999-1007
Slattery, Martha L; Herrick, Jennifer S; Mullany, Lila E et al. (2015) An evaluation and replication of miRNAs with disease stage and colorectal cancer-specific mortality. Int J Cancer 137:428-38
Pellatt, Andrew J; Wolff, Roger K; Herrick, Jennifer et al. (2013) TERT's role in colorectal carcinogenesis. Mol Carcinog 52:507-13
Slattery, Martha L; Lundgreen, Abbie; Wolff, Roger K et al. (2012) Genetic variation in the transforming growth factor-ýý-signaling pathway, lifestyle factors, and risk of colon or rectal cancer. Dis Colon Rectum 55:532-40
Slattery, Martha L; Lundgreen, Abbie; Welbourn, Bill et al. (2012) Oxidative balance and colon and rectal cancer: interaction of lifestyle factors and genes. Mutat Res 734:30-40
Haug, Ulrike; Poole, Elizabeth M; Xiao, Liren et al. (2012) Glutathione peroxidase tagSNPs: associations with rectal cancer but not with colon cancer. Genes Chromosomes Cancer 51:598-605
Poole, Elizabeth M; Curtin, Karen; Hsu, Li et al. (2012) Genetic variability in IL23R and risk of colorectal adenoma and colorectal cancer. Cancer Epidemiol 36:e104-10

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