Abstract

We propose to study the relations between common potentially low-penetrance polymorphisms in candidate genes for breast cancer in three prospective cohorts; the Nurses' Health Studies I and II, and the Women's Health Study. Specific hypotheses relate variants in genes important to steroid hormone metabolism (sex-hormone binding globulin, CYP19 and the progesterone receptor) with risk of breast cancer, and effect modification of the relation of postmenopausal hormone use with breast cancer by genotype. We will also examine polymorphisms in two genes involved in cell cycle control (the HER2 proto- oncogene, the TGF-beta receptor type I) that have been associated with breast cancer risk in other studies. Finally, we will seek to replicate interactions we observed in the current grant cycle between initiation of smoking at a young age and variants in the CYP1A1 gene, and first degree family history of breast cancer and longer (CAG)n repeats in the androgen receptor. We estimate we will accrue 1540 cases of breast cancer in the Nurses' Health Study I, 261 cases in the Nurses' Health Study II, and 1050 cases in the Women's Health Study. With this total of 2851 cases, we will have greater than 90 percent power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and established breast cancer risk factors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA065726-05A1
Application #
6399222
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Seminara, Daniela
Project Start
1995-09-30
Project End
2002-08-31
Budget Start
2001-08-01
Budget End
2002-08-31
Support Year
5
Fiscal Year
2001
Total Cost
$337,188
Indirect Cost

  Institution

Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

Figueroa, Jonine D; Ye, Yuanqing; Siddiq, Afshan et al. (2014) Genome-wide association study identifies multiple loci associated with bladder cancer risk. Hum Mol Genet 23:1387-98
Figueroa, Jonine D; Han, Summer S; Garcia-Closas, Montserrat et al. (2014) Genome-wide interaction study of smoking and bladder cancer risk. Carcinogenesis 35:1737-44
Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E et al. (2014) The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease. Cancer Res 74:5808-18
Corral, Roman; Lewinger, Juan Pablo; Van Den Berg, David et al. (2014) Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai. Int J Cancer 135:335-47
Mitra, Anirban P; Castelao, Jose E; Hawes, Debra et al. (2013) Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program. Cancer 119:756-65
Tao, Li; Day, Billy W; Hu, Bibin et al. (2013) Elevated 4-aminobiphenyl and 2,6-dimethylaniline hemoglobin adducts and increased risk of bladder cancer among lifelong nonsmokers--The Shanghai Bladder Cancer Study. Cancer Epidemiol Biomarkers Prev 22:937-45
Jiang, Xuejuan; Castelao, J Esteban; Yuan, Jian-Min et al. (2012) Cigarette smoking and subtypes of bladder cancer. Int J Cancer 130:896-901
Cash, Haley L; Tao, Li; Yuan, Jian-Min et al. (2012) LINE-1 hypomethylation is associated with bladder cancer risk among nonsmoking Chinese. Int J Cancer 130:1151-9
Cash, Haley L; McGarvey, Stephen T; Houseman, E Andrés et al. (2011) Cardiovascular disease risk factors and DNA methylation at the LINE-1 repeat region in peripheral blood from Samoan Islanders. Epigenetics 6:1257-64
Jiang, Xuejuan; Castelao, J Esteban; Yuan, Jian-Min et al. (2010) Hypertension, diuretics and antihypertensives in relation to bladder cancer. Carcinogenesis 31:1964-71

Showing the most recent 10 out of 33 publications