Wu X, Shi H, Jiang H, Kemp B, Hong W K, Delclos G L, Spitz M R
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Carcinogenesis. 1997 May;18(5):967-73. doi: 10.1093/carcin/18.5.967.
Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of carcinogenic N-nitrosoamines. We therefore assessed the genotype frequencies of PstI or RsaI CYP2E1 restriction fragment length polymorphisms and another susceptibility marker, mutagen sensitivity, in 137 lung cancer cases (92 African American and 45 Mexican American) and 206 controls (114 African American and 92 Mexican American) identified in a molecular epidemiological study of lung cancer. The CYP2E1 c1/c1 genotype was found in 86.7% of Mexican American cases, 70.6% of Mexican American controls, 89.1% of African American cases and 86.8% of African American controls. By multivariate analysis, this genotype was found to be associated with a 14.0-fold increased risk of lung cancer in Mexican Americans but not in African Americans; a 9.9-fold increased risk of lung cancer in Mexican American former smokers, but not in non-smokers or current smokers; a 15-fold increased risk of lung cancer in Mexican American males, but not in females. Patients with the susceptible genotype appeared to have developed cancer at an earlier age and with lower cigarette pack-year of exposure than did patients with the c1/c2 or c2/c2 genotypes. Stratified analysis suggested a greater than multiplicative interaction between cigarette smoking and CYP2E1 c1/c1 genotype, although not statistically significant. The odds ratios (ORs) for the CYP2E1 c1/c1 genotype, cigarette smoking and both risk factors combined were 1.3, 6.7 and 16.3, respectively. The association between CYP2E1 c1/c1 genotype and pack-years of smoking followed the same pattern. The interaction between mutagen sensitivity and CYP2E1 c1/c1 genotype was especially strong in former smokers (the ORs for the CYP2E1 c1/c1 genotype, mutagen sensitivity and both risk factors combined were 3.9, 5.4 and 23.0, respectively). Therefore, the data suggest that individuals who lack a c2 allele might be at higher risk for developing lung cancer.
细胞色素P4502E1（CYP2E1）参与致癌性N-亚硝基胺的代谢活化。因此，我们在一项肺癌分子流行病学研究中，对137例肺癌患者（92例非裔美国人和45例墨西哥裔美国人）和206例对照者（114例非裔美国人和92例墨西哥裔美国人）评估了PstI或RsaI CYP2E1限制性片段长度多态性的基因型频率以及另一个易感性标志物——诱变敏感性。在墨西哥裔美国肺癌患者中，86.7%具有CYP2E1 c1/c1基因型，墨西哥裔美国对照者中该比例为70.6%，非裔美国肺癌患者中为89.1%，非裔美国对照者中为86.8%。多因素分析显示，该基因型与墨西哥裔美国人患肺癌风险增加14.0倍相关，而与非裔美国人无关；与墨西哥裔美国既往吸烟者患肺癌风险增加9.9倍相关，而与不吸烟者或当前吸烟者无关；与墨西哥裔美国男性患肺癌风险增加15倍相关，而与女性无关。具有易感基因型的患者似乎比具有c1/c2或c2/c2基因型的患者患癌年龄更早，且吸烟包年数更低。分层分析提示吸烟与CYP2E1 c1/c1基因型之间存在大于相乘的交互作用，尽管无统计学意义。CYP2E1 c1/c1基因型、吸烟以及两者联合的比值比（OR）分别为1.3、6.7和16.3。CYP2E l c1/c1基因型与吸烟包年数之间的关联遵循相同模式。诱变敏感性与CYP2E1 c1/c1基因型之间的交互作用在既往吸烟者中尤为强烈（CYP2E1 c1/c1基因型、诱变敏感性以及两者联合的OR分别为3.9、5.4和23.0）。因此，数据表明缺乏c2等位基因的个体患肺癌风险可能更高。
