Association of CYP1B1 polymorphisms and breast cancer risk.
Cytochrome P450 1B1 catalyzes the conversion of 17-beta-estradiol (E2) to thecatechol estrogen metabolites 2-OH-E2 and 4-OH-E2 that have been postulated to be involved in mammary carcinogenesis. We sought to determine whether two common functional polymorphisms in Cytochrome P450 1B1, V432L (m1), and A453S (m2) are related to breast cancer risk. Using a nested case control design within the Nurses' Health Study cohort, we genotyped 453 cases and 456 controls and found no significant association between m1[val/leu and leu/leu versus val/val, OR = 1 (CI, 0.72-1.45)] or m2 [asn/ser and ser/ser versus asn/asn, OR = 0.8 (CI, 0.62-1.15)] and breast cancer risk. However, we did observe women with the Val/Val (m1) genotype to have a higher percentage of estrogen receptor-positive tumors (P = 0.03). We did not observe any correlation with the m2 genotypes and estrogen receptor status. The association of the m1 and m2 genotypes on plasma hormone levels in postmenopausal control women not using hormone replacement therapy was also evaluated. Carriers of the m1 leu and m2 ser alleles had modestly higher estradiol levels but similar estrone and estrone sulfate levels. The results presented do not support a strong association between m1 and m2 and the risk of breast cancer.
De Vivo
Immaculata
I
Department of Epidemiology, Harvard Center for Cancer Prevention, Harvard School of Public Health, and the Channing Laboratory, Boston, Massachusetts 02115, USA. Devivo@channing.harvard.edu
Hankinson
Susan E
SE
Li
Lisa
L
Colditz
Graham A
GA
Hunter
David J
DJ
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004958:Estradiol / Q000097:blood / Q000235:genetics; D004970:Estrone / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008593:Menopause; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D013223:Statistics as Topic; D014481:United States / Q000453:epidemiology; D016387:Women's Health
D014408:Biomarkers, Tumor; D004970:Estrone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1