Estrogen exposure is a known risk factor for breast cancer. Phase I enzymes modulate the conversion of estrogen into potentially carcinogenic metabolites. Polymorphisms altering the catalytic function of these enzymes may play an important role in breast cancer risk. CYP1B1 gene single nucleotide polymorphisms (SNPs) resulting in protein alterations (A119S and L432V) have been suggested to impact the conversion of estrogen to carcinogenic metabolites. This study addresses the potential SNP/SNP interaction within the CYP1B1 gene with breast cancer risk using samples collected in an ongoing clinic-based, case-control study (249 cases and 313 controls). Genomic DNA was isolated from blood samples and genotypes were determined by single strand conformation polymorphism analysis. Although not significant, the 119 AS or SS genotypes were associated with a slightly decreased risk of breast cancer (odds ratio [OR]=0.90 or 0.91; 95% confidence interval [95%CI]=0.75-1.08 or 0.76-1.09) compared to AA as the referent group after adjustment for age and age of menarche. The 432 LV or VV genotype was associated with a slightly elevated risk of breast cancer (adjusted OR=1.09 or 1.12; 95%CI=0.90-1.32 or 0.97-1.29) compared to LL as the referent group. In the combined analysis, preliminary data suggested that breast cancer risk was associated with the combined 119 AA and 432 LV/VV genotypes in a three-level model (test for liner trend p=0.09). The OR=1.0 for those without any risk genotype (referent group); the OR=1.26 (95%CI=0.80-1.98) for those with one risk genotype; and the OR=1.46 (95%CI=0.95-2.26) for those with two risk genotypes. With limited sample size, our preliminary findings suggest that the variant alleles for CYP1B1 have opposite effects on breast cancer risk, with the highest risk for breast cancer associated with the combination of 119 AA and 432 LV/VV genotypes.(Supported by NCI grants CA81330, CA73629, and CA91221)

[Proc Amer Assoc Cancer Res, Volume 45, 2004]