Abstract
ISEE-425 Objective: Polymorphism in genes regulating xenobiotic metabolizing enzymes modify the risk of several environmentally induced cancers, but a few studies have examined whether the polymorphism in those genes are related to exposure levels of the suspected environmental pollutants. Material and Methods: We studied the relationship between polychlorinated biphenyls (PCBs) and 11 single nucleotide polymorphisms in AhR, CYP1A1, and CYP2B6 genes regulating xenobiotic metabolism in stored frozen blood samples from 200 subjects (100 men and 100 women) who lived in the vicinity of a former PCB production facility (median for the sum of 15 PCB congeners: 2798 ng/g lipid; 10%–90%: 1386–7870 ng/g lipid). We contrasted the levels of dioxin like mono-ortho substituted congeners (105, 114, 118, 156, 157, 167, and 189) and non–dioxin-like di-ortho substituted congeners (138, 153, 170, and 180) with the studied genetic variants. All analyses were adjusted for age, BMI, and smoking status. Results: Distributions in AhR and CYP2B6 have not been previously described in this population, and we found no genetic variations in 3 of 4 AhR and in 1 of 5 CYP2B6 polymorphisms. The distributions of the 7 remaining polymorphisms were similar to those reported previously in white populations. Variant polymorphisms in exon 7 of CYP1A1 (A4889G), AG/GG variants combined (n = 14) were associated with statistically significantly higher PCB levels for di-ortho PCBs congeners and the sum of 15 congeners (3908 vs. 2548 ng/lipid, and 4471 vs. 2987 ng/g lipid, P = 0.04 and 0.05, respectively). Mono-ortho PCBs were also elevated but did not reach statistical significance. Conclusions: Results of this study suggest that polymorphisms in xenobiotic metabolizing genes might modify body burdens of environmental chemicals, and consequently the individual risk of disease. Confirmation of the reported association with CYP1A1 (A4889G) in larger samples is warranted.
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