Pooled Analyses of Polychlorinated Biphenyls (PCBs) Exposure and CYP1A1 Genetic Polymorphisms on Breast Cancer Risk

Abstract

ISEE-0616 Abstract: An increased risk of breast cancer for women with high polychlorinated biphenyl (PCB) body burden has not been established, however, there is emerging evidence that the association between PCB exposure and breast cancer risk is modified by variants in the CYP1A1 gene. To further examine this relationship we pooled and analyzed data from five existing studies with PCB measurements and CYP1A1 genotypes. We assembled five datasets, consisting of 1838 breast cancer cases and 1989 controls. Pooled odd ratios (ORs) and 95% confidence intervals of breast cancer were assessed for PCB quartiles. CYP1A1 polymorphisms (CYP1A1*2C, CYP1A1*2A) and the interaction between PCB levels and these SNPs were estimated using logistic regression. Analyses were stratified European American (EA) or African American (AA), and menopausal status. In pre-menopausal EA women the odds of breast cancer was almost 1.6 times greater in women with the low versus high PCB levels. This effect was reversed in AA women, such that AA women show a 1.3 increase in odds of breast cancer associated with high versus low PCB levels. The only genetic effect of significance was seen in post-menopausal EA women with the CYP21A1*2C variant, who were found to have a 1.5 fold increase in odds of breast cancer. The combined effect of PCB levels and CYP1A1 genotypes on breast cancer demonstrates a significant interaction between high PCB and the CYP1A1*2C variant in postmenopausal EA women (P = 0.026), causing a two fold increase in odds of breast when compared to women with common allele and low PCB levels. There was no significant interaction with CYP1A1*2A. These analyses demonstrate that PCB body burden modifies the odds of breast cancer in AA and EA women differently and that the association between PCBs burden and breast cancer may be modified by CYP1A1*2C polymorphisms among EA postmenopausal women.