DNA修复基因hOGG1多态与食管癌遗传易感性

Genetic polymorphism in hOGG1 and susceptibility to esophageal cancer in Chinese

目的 研究修复 8-羟基鸟嘌呤的 h OGG1基因 Ser32 6 Cys多态与中国人食管癌易感性的关系。方法 采用病例 -对照分子流行病学方法 ,以 PCR-单链构象多态 (single strand conformationpolymorphism ,SSCP)技术 ,分析了 2 0 1名正常对照和 196例食管癌患者 h OGG1基因第 32 6位 Ser/Ser、Ser/Cys和 Cys/Cys基因型分布 ,并比较不同基因型与食管癌风险的关系。结果 正常人群的 Ser/Ser、Ser/Cys和 Cys/Cys基因型频率分别为 33.8%、5 2 .8%和 13.4%,而食管癌病例组则分别为 39.8%、38.8%和 2 1.4%。虽然两组人群的 Cys等位基因频率基本相同 (39.8%和 40 .8%) ,但食管癌病例组的Cys/Cys基因型频率显著高于对照组 (P<0 .0 5 )。与携带 Ser/Ser或 Ser/Cys基因型者比较 ,携带 Cys/Cys基因型个体患食管癌的风险增加 2倍 (校正 OR=1.9;95 %CI=1.3～ 2 .6 )。吸烟增加食管癌风险 (OR=2 .6 ;95 %CI=1.7～ 3.9) ,但与 h OGG1Cys/Cys基因型无明显协同作用。结论 中国人食管癌易感性与DNA修复基因 h OGG1多态相关 ,h OGG1基因 Ser32 6 Cys多态可能可以作为食管癌遗传易感性标志物 。

Objective To examine the association between Ser326Cys polymorphism in hOGG1 gene, which is involved in the repair of 8 hydroxyguanine in damaged DNA, and investigate the risk of squamous cell carcinoma of the esophagus in Chinese. Methods Ser326Cys polymorphism in hOGG1 gene was determined by PCR SSCP approach among 201 normal controls and 196 patients with squamous cell carcinoma of the esophagus. The association between this genetic polymorphism and the risk of the cancer was examined by a multivariate analysis. Results The Cys/Cys genotype of hOGG1 was found in 21.4% of patients with the cancer and in 13.4% of controls ( P <0.05). Homozygosity for the Cys/Cys genotype significantly increased the risk of developing esophageal cancer, with the odds ratio adjusted for age, sex and smoking being 1.9 (95% CI 1.3 2.6). Smoking also significantly increased esophageal cancer risk in this case control study (adjusted OR 2.6; 95% CI 1.7 3.9). No interaction between smoking and Cys/Cys genotype was observed for the risk of esophageal cancer. Conclusion Polymorphism of hOGG1 Ser326Cys may play a role in esophageal carcinogenesis.