Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Sci Rep. 2017 Feb 2;7:41307. doi: 10.1038/srep41307.
MiR-27a rs895819 is a loop-stem structure single nucleotide polymorphism affecting mature miR-27a function. In this study, we performed a comprehensive analysis about the association of rs895819 with gastric cancer risk and prognosis, atrophic gastritis risk, as well as the interactions with environmental factors. A total of 939 gastric cancer patients, 1,067 atrophic gastritis patients and 1,166 healthy controls were screened by direct sequencing and MALDI-TOF-MS. The association of rs895819 with clinical pathological parameters and prognostic survival in 357 gastric cancer patients was also been analyzed. The rs895819 variant genotype increased the risk for atrophic gastritis (1.58-fold) and gastric cancer (1.24-fold). While in stratified analysis, the risk effect was demonstrated more significantly in the female, age >60y, Helicobacter pylori (H. pylori) negative and non-drinker subgroups. Rs895819 and H. pylori showed an interaction effect for atrophic gastritis risk. In the survival analysis, the rs895819 AG heterozygosis was associated with better survival than the AA wild-type in the TNM stage I-II subgroup. In vitro study by overexpressing miR-27a, cells carrying polymorphic-type G allele expressed lower miR-27a than wild-type A allele. In conclusion, miR-27a rs895819 is implicated as a biomarker for gastric cancer and atrophic gastritis risk, and interacts with H. pylori in gastric carcinogenesis.
miR-27a rs895819 是一个影响成熟 miR-27a 功能的茎环结构单核苷酸多态性。本研究通过直接测序和 MALDI-TOF-MS 对 rs895819 与胃癌风险和预后、萎缩性胃炎风险以及与环境因素的相互作用进行了综合分析。共筛选了 939 例胃癌患者、1067 例萎缩性胃炎患者和 1166 例健康对照者。还分析了 rs895819 与 357 例胃癌患者临床病理参数和预后生存的关系。rs895819 变异基因型增加了萎缩性胃炎（1.58 倍）和胃癌（1.24 倍）的风险。而在分层分析中，女性、年龄>60 岁、幽门螺杆菌（H. pylori）阴性和非饮酒者亚组的风险效应更为显著。rs895819 与 H. pylori 对萎缩性胃炎的风险有交互作用。生存分析显示，TNM 分期 I-II 亚组中，rs895819 AG 杂合子的生存情况优于 AA 野生型。通过过表达 miR-27a 的体外研究，携带多态型 G 等位基因的细胞表达的 miR-27a 低于野生型 A 等位基因。综上所述，miR-27a rs895819 是胃癌和萎缩性胃炎风险的生物标志物，与 H. pylori 相互作用参与胃癌的发生。
