中国人CYP1A1和GSTM1基因多态性及其对个体肺癌易感性的联合效应

目的 在中国江苏肺癌患者和对照人群中，检测CYP1A1 Ile/Val,GSTM1 /0遗传多态性的各基因型及其联合基因型的分布，探讨这些基因型与肺癌个体易感性的关系。方法 配对的病例－对照组各106例，静脉血制备DNA。分别应用等位基因特异性（allele-specific,AS)-PCR和多重差别（multidifferential,MD)-PCR，检测CYP1A1 Ile/Val和GSTM1＋／0的等位基因型。结果 CYP1A1少见等位基因Val/Val纯合子及其与GSTM1基因缺失纯合子（0／0）的联合基因个体，与对照常见基因型个体相比，增加了对肺癌的易感性，其相对危险度（odds ratio,OR)分别为4．02（P＝0．03）和9．38（P＝0．04）；GSTM10／0纯合子及其与CYP1A1 Ile/Val杂合子的联合基因型个体，显著增加了肺癌易感性，其OR值分别是1．92（P＝0．019）和3．27（P＝0．01）。结论 中国江苏人群中，少见基因型CYP1A1 Val/Val,GSTM10/0增加了个体肺癌易感性，在肺癌发生中，上述两种易感基因型间存在协同或相乘作用。

Polymorphisms of the CYP1A1 and GSTM1 genes and their combined effects on individual susceptibility to lung cancer in a Chinese population

OBJECTIVE: To investigate the polymorphisms of CYP1A1 and GSTM1 genes as well as their separate and combined effects on individual susceptibility to lung cancer. METHODS: In the matched 106 pairs of patients with lung cancer and non-cancer control persons, genomic DNA were prepared from peripheral blood samples. The genotypes of CYP1A1 Ile/Val and GSTM1+/0 polymorphisms were detected by the allele-specific(AS)-PCR and multidifferential(MD)-PCR. RESULTS: Individuals with genotype Val/Val of CYP1A1, genotype 0/0 of GSTM1, combined genotypes GSTM1 0/0 and CYP1A1 Val/Val, or combined genotypes GSM1 0/0 and CYP1A1 Ile/Val had higher relative risk than those with the corresponding common genotypes and combined genotypes; their odds ratios were 4.02(P=0.03), 1.92(P=0.019), 9.38(P=0.04) and 3.27(P=0.01), respectively. CONCLUSION: There is a synergy of susceptible genotypes GSTM1 0/0 and CYP1A1 Val/Val or CYP1A1 Ile/Val to enhance the individual susceptibility to lung cancer.