Genetic polymorphism of cytochrome P450-1B1 and risk of breast cancer

Cytochrome P450-1B1 (CYP1B1) is a major enzyme catalyzing the formation of genotoxic 4-hydroxyestradiol. This enzyme is also involved in the activation of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, mammary carcinogens in experimental animals. CYP1B1 is genetically polymorphic, and the variations in the CYP1B1 gene may be related to the risk of breast cancer. We evaluated this hypothesis among 186 breast cancer cases and 200 age-matched controls as part of a large population-based case-control study conducted in urban Shanghai during 1996 to 1998. Genomic DNA from cases and controls was analyzed for genetic polymorphism in codon 432 (Val-->Leu) of the CYP1B1 gene using a PCR-RFLP-based assay. The frequency of the Leu allele was 53% in cases and 46% in controls (P = 0.06). Compared with those with the Val/Val genotype, women with the Leu/Leu genotype had a 2.3-fold [95% confidence interval (CI), 1.2-4.5] elevated risk of breast cancer after adjusting for potential confounding variables. This positive association was more pronounced among postmenopausal women (Odds ratio, 3.1; 95% CI, 1.0-9.1) than premenopausal women (OR, 1.9; 95% CI, 0.8-4.3). Elevated risks of breast cancer associated with homozygosity for the Leu allele were observed in virtually all subgroups of women defined by major risk factors for breast cancer. The results from this study were consistent with recent findings from in vitro and animal experiments implicating a potentially important role of CYP1B1 in the etiology of human breast cancer.