Serum Polychlorinated Biphenyls, Cytochrome P-450 1A1 Polymorphisms, and Risk of Breast Cancer in Connecticut Women

Abstract

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.

Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis

“…Concerning the C2453A polymorphism, 11 studies were eligible (7,189 cases and 8,491 controls) [34,35,41,44,49,56,57,64,67]; nine studies on Caucasians (6,859 cases and 8,147 controls) [34,35,41,44,49,56,57,64,67]; and two studies on African subjects (330 cases and 344 controls) [34,41].…”

“…Specifically, the pooled ORs pertaining to Caucasians were as follows: 0.986 (0.796-1.220, random effects) for heterozygous carriers, 2.317 (1.290-4.160, fixed effects) for homozygous carriers, 1.068 (0.869-1.313, random effects) for the dominant model, and 2.221 (1.239-3.982, fixed effects) for the recessive model. Worthy of note, however, the deviation from HWE could not be assessed due to reporting reasons in five studies [32,49,54,59,65].…”

Clinical, Cytogenetic and CYP1A1 exon-1 Gene Mutation Analysis of Beedi Workers in Vellore Region, Tamil Nadu

“…In this study between tobacco use and presence of CYP1A1 gene polymorphism confirmed that higher incidence of presence of CYP1A1 polymorphism in populations with tobacco intake. Toxicological studies support that environmental toxicants like polychlorinated biphenyls induce CYP1A1 to metabolize environmental carcinogens into highly reactive intermediates, potentially resulting in DNA damage and ultimately carcinogenesis (Zhang et al, 2004).…”

Gender and Age Related Modulation of Xenoestrogen-Induced Tumorigenesis

“…Thus, the interaction between the lack of both glutathione S-transpherase (GST) M1 and GSTT1 genes and alcohol consumption significantly increase breast cancer in premenopausal women [44]. Epidemiologic studies have suggested that the exposure to the bioaccumulating pollutants polychlorinated biphenyls (PCBs) increases breast cancer risk in women with m2 polymorphism in the cytochrome P-450 1A1 gene (CYP1A1); the risk was more elevated in postmenopausal women [45]. Dietary habits may also influence the susceptibility to EDCs, both by modulating exposure (e.g., certain fishing communities are highly exposed to bioaccumulating pollutants) and, most important by modulating the organism's susceptibility through the intake of nutrients and bioactive food components [46].…”

“…The cancer risk may be modulated by metabolic polymorphisms. Increased risk of breast cancer in women exposed to polychlorinated biphenyls was highest in carriers of CYP1A1 m2 variant genotype, especially for those women who were in postmenopausal period [45]. Interestingly, the risk of breast cancer is lower in women who had children and did breast feed them; this protective effect of breast feeding in mothers may occur at the expense of the newborns, as milk is an effective way to excrete fat soluble xenoestrogens, thus reducing the maternal body burden.…”