Copyright © 2004 by the Johns Hopkins Bloomberg School of Public Health
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Serum Polychlorinated Biphenyls, Cytochrome P-450 1A1 Polymorphisms, and Risk of Breast Cancer in Connecticut Women
1 Department of Epidemiology and Public Health, School of Medicine, Yale University, New Haven, CT.
2 Department of Applied Medical Sciences, School of Applied Science, Engineering, and Technology, University of Southern Maine, Portland, ME.
3 Department of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
5 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT.
6 Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.
Recent epidemiologic studies have suggested that genetic polymorphisms in the cytochrome P-450 1A1 gene (CYP1A1) may affect the relation between environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk. The authors report results from a case-control study evaluating the potential effect of gene-environment interaction between CYP1A1 and serum PCB levels on breast cancer risk among Caucasian women in Connecticut. The study included 374 case women with histologically confirmed breast cancer and 406 noncancerous controls with information on both serum PCB level and CYP1A1 genotype (1999–2002). Compared with women who had the homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 variant genotype (odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.1, 3.9), especially postmenopausal women (OR = 2.4, 95% CI: 1.1, 5.0). Risks associated with the CYP1A1 m2 variant genotype were highest for all women (OR = 3.6, 95% CI: 1.5, 8.2) and postmenopausal women (OR = 4.3, 95% CI: 1.6, 12.0) with higher serum PCB levels (611–2,600 ng/g). The CYP1A1 m1 and m4 genotypes were not associated with breast cancer risk independently or in combination with PCB exposure. In summary, the CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer and may modify the relation between PCB exposure and breast cancer risk.
breast neoplasms; cytochrome P-450 enzyme system; genetics; polychlorinated biphenyls; polymorphism (genetics); risk factors; women
Abbreviations: Abbreviations: AHH, aryl hydrocarbon hydroxylase; CI, confidence interval; CYP1A1, cytochrome P-450 1A1; OR, odds ratio; PCB(s), polychlorinated biphenyl(s); PCR, polymerase chain reaction.
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