hMSH2基因剪切调控区域多态与家族性、低龄胃癌发病的关系

Association between polymorphisms in the splicing regulatory region of hMSH2 gene and incidence of familial or under-50 age gastric cancer

目的研究hMSH2基因IVS10+12G>A、IVS12-6T>C多态与家族性、低龄胃癌发病的相关性。方法分别在江苏省北部、中部和南部的肿瘤高发区选择淮安、泰州及金坛3个地区以现场调查的方式,收集100例家族性、149例散发性同年新发胃癌患者及260例健康人的外周血标本,同时记录饮食习惯等生活因素资料。提取外周血细胞的DNA,应用PCR-变性高效液相色谱(DHPLC)和DNA测序技术检测hMSH2基因多态,结合流行病学资料采用病例对照研究方法进行分析。结果 249例胃癌患者中hMSH2基因IVS10+12G>A、IVS12-6T>C基因型的检出率高于260例正常对照(P<0.05)。两个基因型有联合作用,并主要分布于家族性胃癌患者中,与正常对照差异显著(P<0.05),而在散发性胃癌患者与正常对照之间则无明显差异(P>0.05)。对混杂因素的分层分析显示,hMSH2基因IVS10+12G>A、IVS12-6T>C多态主要存在于<50岁的患者中(P<0.05),与食用腌菜有显著的相关性(P<0.05)。结论 hMSH2基因IVS10+12G>A、IVS12-6T>C多态是国人家族性、低龄(<50岁)胃癌的发病风险因素,且两种多态性有叠加作用,可作为胃癌风险评估的指标。

Objective To investigate the association between IVS10 ＋ 12G 〉 A and IVS12 - 6T 〉 C polymorphisms in the hMSH2 gene and incidence of familial or under 50 age gastric cancer. Methods A case-control study has been taken on subjects in- cluding 149 sporadic cases, 100 familial cases and 260 healthy individual controls to investigate whether such polymorphisms affecting the risk of developing gastric cancer. Peripheral blood cell DNA was obtained from all subjects. IVS10 ＋ 12 G 〉 A and IVS12 -6T 〉 C polymorphisms in hMSH2 gene were detected using a PCR-based DHPLC and verified by DNA sequencing. Results The frequencies of IVS10 ＋ 12 G 〉 A and IVS12 -6T 〉 C polymorphisms in 249 patients were significantly higher than those in 260 controls. IVS10 ＋ 12 G 〉 A and IVS12 - 6T 〉 C polymorphisms jointly affected the onset of gastric cancer,especially in familial cases. No difference was found between 149 sporadic patients and 260 controls. The stratification analysis of confounding factors showed that hMSH2 gene IVS10 ＋ 12 G 〉 A and IVS12 - 6 T 〉 C polymorphisms exist mainly in under 50 age patients （ P 〈 0. 05 ） , and significantly correlated with sauerkraut dietary factor（ P 〈 0.05 ）. Conclusion The IVS10 ＋ 12G 〉 A and IVS12 - 6T 〉 C polymorphisms in hMSH2 gene are asso- ciated with increased risk of developing gastric cancer in familial or under 50 age population. Determination of these polymorphisms may be suitable to identify individuals with increased risk of gastric cancer.