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Polychlorinated Biphenyls, Cytochrome P450 1A1, and Breast Cancer Risk in the Nurses’ Health Study¹

Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 [F. L., S. E. H., D. J. H.]; Departments of Environmental Health [F. L., K. T. K.], Epidemiology [S. E. H., D. J. H.], and Cancer Cell Biology [K. T. K.], Harvard School of Public Health, Boston, Massachusetts; Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland [N. I.]; Mount Sinai Medical School, New York New York [M. S. W.]; Centre for Genetic Epidemiology, School of Population Health, University of Melbourne, Carlton, Australia [D. M. G.]; and Harvard Center for Cancer Prevention, Harvard School of Public Health, Boston Massachusetts 02115 [D. J. H., K. T. K.]

There is concern that exposures to the environmental chemicals polychlorinated biphenyls (PCBs) may contribute to breast cancer risk. An individual’s susceptibility to the effects of PCBs may be partially determined by polymorphisms in the gene encoding the biotransformation enzyme cytochrome P450 1A1 (CYP1A1). PCB exposure induces CYP1A1 activity, and PCBs themselves or other xenobiotics can be metabolized to carcinogenic intermediates in the presence of the variant genotype. A previous case-control study provided evidence of an interaction between high exposures to PCBs and the CYP1A1-exon 7 polymorphism (the A to G transition at nucleotide 4889), leading to a significant increase in postmenopausal breast cancer risk. We examined the interaction of PCBs with the CYP1A1-MspI (the T to C transition at nucleotide 6235) and exon 7 polymorphisms among 367 breast cancer case-control pairs (293 postmenopausal pairs) in the Nurses’ Health Study. Although there was no independent association of either the CYP1A1 variants or PCBs with breast cancer risk, the relative risk among the postmenopausal women with plasma PCB levels in the highest third of the distribution in the control group and at least one exon 7 variant allele compared with women who were homozygous for the wild-type allele and who had PCB levels in the lowest third was 2.78 (95% confidence interval, 0.99–7.82). The majority of studies have concluded that exposure to PCBs is unlikely to be a major cause of breast cancer, but these findings indicate that further studies of genetically susceptible populations are warranted.

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