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 that have been linked to colon cancer. In this study, we will evaluate DNA obtained from tumor tissue from cases enrolled in a large population-based case-control study of colon cancer (CA61757; CA 48998); we propose to collect tumor blocks from a population-based case-control study of rectal cancer to further evaluate associations (continuation of CA48998). Tumor DNA will be analyzed to determine specific mutations and CIMP pathway phenotype. We will evaluate the associations between these genetic mutations and tumor stage at diagnosis and survival. These data will be linked to environmental data, that 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 the CIMP phenotype. Using data from the original studies, we will use statistical methods to better define disease pathways. We will include previously collected information on p53, K-ras, and microsatellite instability in tumors as well as information on CIMP phenotype. Rectal tumors will be characterized in the same manner as colon cancer tumors were originally characterized (i.e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA061757-06A1
Application #
6471825
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Whitted, Jacqueline
Project Start
1995-08-01
Project End
2007-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
6
Fiscal Year
2002
Total Cost
$1,035,013
Indirect Cost
Name
University of Utah
Department
Internal Medicine/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
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
Slattery, Martha L; Herrick, Jennifer S; Bondurant, Kristina L et al. (2012) Toll-like receptor genes and their association with colon and rectal cancer development and prognosis. Int J Cancer 130:2974-80
Slattery, Martha L; Lundgreen, Abbie; Herrick, Jennifer S et al. (2012) Genetic variation in bone morphogenetic protein and colon and rectal cancer. Int J Cancer 130:653-64

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