Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk

In experimental systems, polychlorinated biphenyls (PCBs) induce cytochrome P4501A1 (CYP1A1), which is involved in metabolism of steroid hormones and polycyclic aromatic hydrocarbons in humans. A genetic polymorphism coding f or a valine to isoleucine substitution in exon 7 has been associated with l ung cancer risk in Japanese populations. In a previous study, we found no a ssociation between CYP1A1 genotype and breast cancer risk. However, we were interested in determining whether genotype would relate to risk when PCB b ody burden was taken into account. In a subset of a ease-control study in w estern New York, 154 postmenopausal women with incident, primary, histologi cally confirmed postmenopausal breast cancer and 192 community controls wer e interviewed and underwent phlebotomy. Serum levels of 56 PCB peaks were d etermined by high resolution gas chromatography with electron capture. PCR- RFLP analyses of the CYP1A1 polymorphism were performed. Unconditional logi stic regression was used to compute adjusted odds ratios and 95% confidence intervals. Among women with serum PCB levels above the median of the distr ibution in the control group, there was increased risk of breast cancer ass ociated with the presence of at least one valine allele, compared with wome n who were homozygous for the isoleucine alleles (odds ratio, 2.93; 95% con fidence interval, 1.17-7.36), Among women with low PCB body burden, no asso ciation between CYP1A1 genotype and breast cancer risk was observed, Adjust ment for serum lipids and body mass index did not affect the magnitude of t he observed associations. PCB body burden may modify the effect of the poly morphism on postmenopausal breast cancer risk through increased CYP1A1 enzy me induction or by activation by specific PCB congeners, These results shou ld be considered preliminary, pending replication by other studies.