Mammographic density is currently considered our best surrogate endpoint for breast cancer risk. However, determinants of mammographic density are not well understood. Age, menopausal status, body size, and parity collectively explain less than half of the total variance in mammographic density. The main objective of this grant application is to follow-up on our previous leads on dietary and genetic determinants of mammographic density. We propose to conduct a cost-effective cross-sectional study among 2,200 postmenopausal Chinese women in Singapore who were participants of both the Singapore Chinese Health Study, a prospective cohort study of cancer, and the nationwide mammography screening program. As part of entry into the cohort study, these women were interviewed in person and provided detailed lifestyle information and completed a validated 165-item food frequency questionnaire. Blood specimens (for genotyping) and mammograms are already available on these 2,200 women. We propose to assess mammographic density using a computer-assisted method we developed and have successfully employed in epidemiological and clinical studies. Our primary specific aims are: (1) To assess diet, especially soy intake, in relation to mammographic density. In addition, we will assess the potential modifying and/or confounding effect of dietary factors such as dietary fat, fiber, carotenoids, cruciferous vegetables/isothiocyanates, on the soy-mammographic density association. (2) To assess whether genotypes modify the associations between dietary factors (such as soy intake) and mammographic density. For example, we will evaluate whether the associations between estrogen metabolizing genes (e.g., HSD17B1, CYP1B1, COMT, SULT1A1) and mammographic density are stronger among low soy consumers. Our secondary specific aims are: (3) To assess genotypes of a panel of sex-steroid hormone metabolism genes, in relation to mammographic density. (4) To assess genotypes of other mitogenesis-related genes including the angiotensin I-converting enzyme (ACE), transforming growth factor beta-1(TGFbeta-1), insulin-like growth factor- I (IGF-1) and IGF binding protein (BP)-3), in relation to mammographic density.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA102065-05
Application #
7414568
Study Section
Special Emphasis Panel (ZRG1-BMRD (02))
Program Officer
Mahabir, Somdat
Project Start
2004-05-01
Project End
2012-04-30
Budget Start
2008-05-01
Budget End
2012-04-30
Support Year
5
Fiscal Year
2008
Total Cost
$272,834
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Wu, Anna H; Stanczyk, Frank Z; Wang, Renwei et al. (2013) Sleep duration, spot urinary 6-sulfatoxymelatonin levels and risk of breast cancer among Chinese women in Singapore. Int J Cancer 132:891-6
Lee, Eunjung; Van Den Berg, David; Hsu, Chris et al. (2013) Genetic variation in transforming growth factor beta 1 and mammographic density in Singapore Chinese women. Cancer Res 73:1876-82
Lee, Eunjung; Su, Yu-Chen; Lewinger, Juan Pablo et al. (2013) Hormone metabolism genes and mammographic density in Singapore Chinese women. Cancer Epidemiol Biomarkers Prev 22:984-6
Wu, Anna H; Yu, Mimi C (2013) Author's reply to: Sleep duration, melatonin and breast cancer in the Singapore Chinese Health Study: on null results and their interpretation. Int J Cancer 133:2012
Qureshi, Samera Azeem; Couto, Elisabeth; Hofvind, Solveig et al. (2012) Alcohol intake and mammographic density in postmenopausal Norwegian women. Breast Cancer Res Treat 131:993-1002
Wu, Anna H; McKean-Cowdin, Roberta; Tseng, Chiu-Chen (2011) Birth weight and other prenatal factors and risk of breast cancer in Asian-Americans. Breast Cancer Res Treat 130:917-25
Wu, Anna H; Butler, Lesley M (2011) Green tea and breast cancer. Mol Nutr Food Res 55:921-30
Qureshi, Samera Azeem; Couto, Elisabeth; Hilsen, Marit et al. (2011) Mammographic density and intake of selected nutrients and vitamins in Norwegian women. Nutr Cancer 63:1011-20
Butler, Lesley M; Wu, Anna H; Wang, Renwei et al. (2010) A vegetable-fruit-soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women. Am J Clin Nutr 91:1013-9
Wu, Anna H; Ursin, Giske; Koh, Woon-Puay et al. (2008) Green tea, soy, and mammographic density in Singapore Chinese women. Cancer Epidemiol Biomarkers Prev 17:3358-65

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