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 & 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.