Association between the T27C polymorphism in the cytochrome P450 c17alpha (CYP17) gene and risk factors for breast cancer.
Mammographic density is associated with increased breast cancer risk and is influenced by sex hormones. A T27C polymorphism (alleles A1 and A2, respectively) in the 5' promoter region of CYP17 may be associated with elevated sex hormone levels. In a cross-sectional study of 181 pre- and 173 postmenopausal women, we examined the relationship of this polymorphism with mammographic density and other risk factors for breast cancer. Subjects were recruited across five categories of density. Risk factor and dietary information, anthropometric measures, and blood samples were obtained. Sex hormone, lipid, growth factor levels, and CYP17 genotypes were determined. CYP17 genotype was not associated with mammographic density levels before or after adjusting for risk factors for breast cancer. In premenopausal women, the A2 allele was associated with higher levels of dehydroepiandrosterone sulfate, and in postmenopausal women, with higher levels of total estradiol and lower levels of follicle stimulating hormone. Among premenopausal women, interactions were observed between CYP17 genotype and endogenous insulin levels as well as dietary variables associated with mammographic density. Our findings suggest that the CYP17 A2 allele is associated with hormone levels, and interacts with insulin levels and diet to affect breast density levels and potentially breast cancer risk.
Hong
Chi-Chen
CC
Division of Epidemiology and Statistics, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.
Thompson
Henry J
HJ
Jiang
Cheng
C
Hammond
Geoffrey L
GL
Tritchler
David
D
Yaffe
Martin
M
Boyd
Norman F
NF
D000328:Adult; D001940:Breast / Q000503:physiopathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008327:Mammography; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D012739:Gonadal Steroid Hormones; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013254:Steroid 17-alpha-Hydroxylase