胃癌易感性与诱导型一氧化氮合酶基因多态性关系的研究

Study on the Relationship between susceptibility of stomach neoplasm cancer and polymorphism of inducible Nitric Oxide Synthase gene

目的 探讨中国人诱导型一氧化氮合酶 (iNOS)基因多态性与胃癌易感性的关系。方法 以社区为基础的病例对照研究。病例经胃镜及病理确诊 ,有效分析样本包括肠型胃癌 93例 ,胃贲门癌 5 0例 ,对照 2 4 6人。结果 iNOS基因第 16外显子存在C→T多态性 (产生Tsp 5 0 9Ⅰ内切酶的识别位点 ) ,使编码的氨基酸由丝氨酸 (Ser)改变为亮氨酸 (Leu) ,对照人群T等位基因频率为13.2 1% ,单独存在C→T多态性与肠型胃癌、胃贲门癌易感性增加无统计学关联 ,但与吸烟因素同时存在 ,对肠型胃癌、胃贲门癌产生明显的 2型超相乘交互作用 ;与缺乏CagA抗体同时存在 ,对胃贲门癌产生明显的相加交互作用。结论 iNOS基因C→T多态性可能是胃癌的易感基因 ,特别与吸烟、缺乏幽门螺杆菌CagA抗体的肠型胃癌、胃贲门癌发生密切相关。

Objective To study the relationship between polymorphism of inducible Nitric Oxide Synthase (iNOS) gene and the susceptibility of intestinal type stomach cancer and stomach cardia cancer in Chinese people. Methods A community based case control study was designed. Ninety three intestinal type of stomach cancer and 50 stomach cardia cancer patients with endoscopy and pathology diagnosis were identified as cases. Two hundred and forty six controls served as controls. Results C→T polymorphism was found in exon 16 of iNOS gene, which changed the coding amino acid from serine to leucine, and formed a recognition site identified by Tsp 509Ⅰ restriction enzyme (we called it C→T polymorphism). The T allele gene frequency in the control group was 13.21 %. No statistically significant difference was found between C→T polymorphism alone and the increased susceptibility to intestinal stomach cancer or stomach cardia cancer. A significant type 2 multiplicative interaction was found in increasing both the risk of intestinal stomach cancer and stomach cardia cancer when both C→T polymorphism and tobacco smoking exposure existed. An additive interaction model, which showed statistically significant difference, was found to increase only the risk of stomach cardia cancer when CagA antibody shared negative but C→T polymorphism occurred. Conclusion C→T polymorphism of iNOS gene was considered as one of the possible susceptible genes, which specifically increased the risk of tobacco related but CagA negative types of intestinal stomach cancer and stomach cardia cancer. [