出版社：National Institute of Occupational Safety and Health
摘要：Although cigarette smoking is one major determinant of lung carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens, nutrition, and lifestyle. Previous studies have shown that genetic polymorphism of metabolic enzymes and plasma micronutrients are associated with lung cancer risk. DNA adducts may serve as a molecular dosimeter for exposure to carcinogens. In this cross-sectional study, we analyzed the blood samples of 158 subjects to evaluate the effects of polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase M1 (GSTM1, T (GSTT)), N-acetytransferase 2 (NAT2), and aldehyde dehydrogenase 2 (ALDH2) as well as the effects of plasma β-carotene and α-tocopherol on lymphocyte DNA adducts measured by 32P-postlabeling analysis. The DNA adduct level of smokers (mean±SD, 1.26±0.79/108 nucleotides) was significantly higher than that of nonsmokers (0.87±0.33, P=0.007). Smokers with CYP1A1 minor homozygotes and GSTM1 null genotypes had a significantly higher level of DNA adducts than those without (P=0.027 for homozygotes, P=0.049 for heterozygotes). Smokers with NAT2 minor homozygotes also tended to have a higher DNA adduct level than those with heterozygotes and wild alleles, but the difference was not statistically significant. The DNA adduct level of smokers with ALDH2 heterozygotes was significantly higher than that of smokers with minor homozygotes (P=0.045). When smokers were divided into “high” and “low” groups according to mean level of plasma β-carotene or α-tocopherol, in the low β-carotene group, the subjects with CYP1A1 minor homozygotes had higher DNA adduct levels than those with other CYP1A1 genotypes. Smokers with GSTT null genotype and high β-carotene tended to have a higher DNA adduct level than those with GSTT present and high β-carotene (P=0.07), and those with GSTT null genotype and low β-carotene (P=0.07). There was weak correlation between DNA adduct level and number of cigarettes smoked per day in the low plasma β-carotene group (r=0.28, n=36, p<0.1). These results suggested that polymorphisms of CYP1A1, GSTM1, T, NAT2, and ALDH2, and plasma β-carotene may modulate the level of DNA adducts.
