Yang Chao, Ma Xiang, Liu Dongxiao, Wang Younan, Tang Ran, Zhu Yi, Xu Zekuan, Yang Li
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Tumour Biol. 2014 Dec;35(12):12545-54. doi: 10.1007/s13277-014-2574-9. Epub 2014 Sep 5.
More and more evidence reveals that noncoding RNA miR-34b/c and tumor suppressor gene TP-53 independently, and/or jointly, play crucial roles in carcinogenesis. The purpose of the present hospital-based case-control study was to investigate the association between the miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of gastric cancer. Two polymorphisms were genotyped in 419 gastric cancer patients and 402 age- and sex-matched cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism analysis. The CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of gastric cancer compared with the TT genotype and T allele (CC vs. TT: P = 0.006, adjusted odds ratio (OR) = 0.53, 95 % confidence interval (95 % CI) = 0.34-0.83; C vs. T: P = 0.005, adjusted OR = 0.75, 95 % CI = 0.61-0.92). Compared with individuals with the wild-type TT genotype, subjects with the variant genotypes (CT + CC) had a significantly decreased risk of gastric cancer (P = 0.047, adjusted OR = 0.75, 95 % CI = 0.57-0.99). Stratified analysis showed that the association between the risk of gastric cancer and the variant genotypes of miR-34b/c was more profound among men. However, no overall association was found between the TP53 Arg72Pro polymorphism and gastric cancer risk. In the combined analysis, no effects of the interaction of miR-34b/c rs4938723 and TP53Arg72Pro on gastric cancer risk were observed. Our findings indicate that the miR-34b/c rs4938723 CT/CC genotypes may be associated with a decreased risk of gastric cancer and the C allele may be a protective factor in gastric cancer.
越来越多的证据表明,非编码RNA miR - 34b/c和肿瘤抑制基因TP - 53在致癌过程中独立和/或共同发挥关键作用。本基于医院的病例对照研究旨在探讨miR - 34b/c rs4938723和TP53 Arg72Pro基因多态性与胃癌风险之间的关联。采用聚合酶链反应 - 限制性片段长度多态性分析对419例胃癌患者和402例年龄及性别匹配的无癌对照进行了两种多态性的基因分型。与TT基因型和T等位基因相比,miR - 34b/c rs4938723的CC基因型和C等位基因与胃癌风险显著降低相关(CC与TT比较:P = 0.006,调整后的比值比(OR)= 0.53,95%置信区间(95%CI)= 0.34 - 0.83;C与T比较:P = 0.005,调整后的OR = 0.75,95%CI = 0.61 - 0.92)。与野生型TT基因型个体相比,携带变异基因型(CT + CC)的受试者患胃癌的风险显著降低(P = 0.047,调整后的OR = 0.75,95%CI = 0.57 - 0.99)。分层分析表明,miR - 34b/c变异基因型与胃癌风险之间的关联在男性中更为显著。然而,未发现TP53 Arg72Pro基因多态性与胃癌风险之间存在总体关联。在联合分析中,未观察到miR - 34b/c rs4938723与TP53Arg72Pro相互作用对胃癌风险的影响。我们的研究结果表明,miR - 34b/c rs4938723的CT/CC基因型可能与胃癌风险降低相关,且C等位基因可能是胃癌的一个保护因素。