This proposal is for a population-based case-control study of breast cancer in Nashville, Tennessee. The primary hypotheses are 1) regular use of nonsteroidal anti-inflammatory drugs (NSAID) may reduce the risk of breast cancer, and this association may be modified by the genotypes of NSAID metabolizing enzymes;2) well-done (charred) meat intake, and thus exposures to the mammary carcinogens heterocyclic amines and polycyclic aromatic hydrocarbons, may be related to an increased risk of breast cancer, particularly among women with certain genotypes of the carcinogen-metabolizing enzymes;3) the positive association between well-done meat intake and breast cancer risk may be modified by regular NSAID use;4) certain polymorphic genes involved in estrogen metabolism may interact with each other in the etiology of breast cancer. We propose to recruit 1,500 incident cases and 1,500 controls for this case-control study. Breast cancer cases will be identified through a rapid case-ascertainment system established for the study. Controls will be selected randomly from the general population and frequency-matched to cases by age and race. Telephone interviews will be conducted to obtain relevant exposure information. Exfoliated buccal cell samples will be collected to extract DNA for analyzing 38 polymorphisms in 14 candidate genes that are involved in the metabolism of NSAIDs, mammary carcinogens, and estrogens. DNA samples will also be stored for future studies of additional genetic factors and their interactions with lifestyle factors in the risk of breast cancer. NSAIDs are among the most commonly used medications, and high-temperature cooking has been widely used for meat preparation. Information regarding their associations with breast cancer risk could have important public health implications in the primary prevention of breast cancer. Studies investigating gene-gene and gene-environment interaction could provide valuable information in identifying high-risk individuals for designing cost-effective preventive strategies for breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA100374-05S1
Application #
7926359
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Nelson, Stefanie A
Project Start
2004-06-01
Project End
2011-04-30
Budget Start
2009-09-01
Budget End
2011-04-30
Support Year
5
Fiscal Year
2009
Total Cost
$385,325
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Michailidou, Kyriaki (see original citation for additional authors) (2017) Association analysis identifies 65 new breast cancer risk loci. Nature 551:92-94
Gao, Guimin; Pierce, Brandon L; Olopade, Olufunmilayo I et al. (2017) Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer. PLoS Genet 13:e1006727
Milne, Roger L (see original citation for additional authors) (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49:1767-1778
Hoffman, Joshua D; Graff, Rebecca E; Emami, Nima C et al. (2017) Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk. PLoS Genet 13:e1006690
Feng, Ye; Rhie, Suhn Kyong; Huo, Dezheng et al. (2017) Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry. Cancer Epidemiol Biomarkers Prev 26:1016-1026
Liu, Jingjing; Lon?ar, Ivona; Collée, J Margriet et al. (2016) rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk. Sci Rep 6:36874
Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud et al. (2016) Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs). Sci Rep 6:32512
Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan et al. (2016) No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. J Med Genet 53:298-309
Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2 (see original citation for additional authors) (2016) No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecol Oncol 141:386-401
Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki et al. (2016) Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry. Cancer Causes Control 27:679-93

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