PT - JOURNAL ARTICLE AU - Hong, Chi-Chen AU - Thompson, Henry J. AU - Jiang, Cheng AU - Hammond, Geoffrey L. AU - Tritchler, David AU - Yaffe, Martin AU - Boyd, Norman F. TI - Val158Met Polymorphism in <strong><em>Catechol-O-methyltransferase</em></strong> Gene Associated with Risk Factors for Breast Cancer DP - 2003 Sep 01 TA - Cancer Epidemiology Biomarkers &amp; Prevention PG - 838--847 VI - 12 IP - 9 4099 - http://cebp.aacrjournals.org/content/12/9/838.short 4100 - http://cebp.aacrjournals.org/content/12/9/838.full SO - Cancer Epidemiol Biomarkers Prev2003 Sep 01; 12 AB - Extensive mammographic density is heritable, strongly associated with increased breast cancer risk, and is influenced by sex hormone exposure. In a cross-sectional study of 181 pre- and 171 postmenopausal women without breast cancer, we examined the relationship of a functional polymorphism in catechol-O-methyltransferase (COMT; VAL→MET) to mammographic density and other risk factors for breast cancer. We hypothesized that individuals who inherited the low-activity form of COMT (COMT*2 allele) would have higher levels of breast density, presumably because of reduced inactivation/ detoxification of catecholestrogens. Subjects were recruited across five categories of breast density. Risk factor information, anthropometric measures, and blood samples were obtained; sex hormone and growth factor levels were measured, and COMT genotypes determined. Mammograms were digitized and measured using a computer-assisted method. After adjustment for age and ethnicity, among pre- but not postmenopausal subjects, each low-activity COMT*2 allele was associated with lower levels of percentage breast density. The statistical significance of this association was lost after further adjustment for serum growth factors [growth hormone, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3)], hormones [follicle-stimulating hormone (FSH) and progesterone], and body size (body mass index and waist:hip ratio). The low-activity COMT*2 allele was also associated, after adjustment for age and ethnicity in premenopausal women, with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist:hip ratio, body mass index, and subscapular skinfold. After adjustment for body size, the associations of genotype with IGFBP-3 and FSH were no longer significant. These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women.