Liu Yao, Zhang Qin, Ren Chuanli, Ding Yanbing, Jin Guangfu, Hu Zhibin, Xu Yaochu, Shen Hongbing
Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
J Biomed Res. 2012 Sep;26(5):315-8. doi: 10.7555/JBR.26.20110087. Epub 2012 Mar 29.
MET tyrosine kinase and its ligand, hepatocyte growth factor (HGF), play a pivotal role in the activties of tumor cells. A germline missense variant in exon 2 of the MET gene, N375S (rs33917957 A>G), may alter the binding affinity of MET for HGF and thus modify the risk of tumorigenesis. In this study, we performed a case-control study to assess the association between N375S and gastric cancer risk in 1,681 gastric cancer cases and 1,858 cancer-free controls. Logistic regression analysis was applied to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and gastric cancer risk. We found that MET N375S variant genotypes (NS/SS) were associated with a significantly decreased risk of gastric cancer (OR = 0.78, 95% CI = 0.63-0.96, P = 0.021) compared with the wildtype homozygote (NN). The finding indicates that this germline variant in MET may decrease gastric cancer susceptibility in Han Chinese.
MET酪氨酸激酶及其配体肝细胞生长因子(HGF)在肿瘤细胞活性中起关键作用。MET基因第2外显子中的一种种系错义变体N375S(rs33917957 A>G)可能会改变MET与HGF的结合亲和力,从而改变肿瘤发生风险。在本研究中,我们进行了一项病例对照研究,以评估1681例胃癌病例和1858例无癌对照中N375S与胃癌风险之间的关联。应用逻辑回归分析来估计基因型与胃癌风险之间关联的粗比值比(OR)和调整比值比以及95%置信区间(CI)。我们发现,与野生型纯合子(NN)相比,MET N375S变异基因型(NS/SS)与胃癌风险显著降低相关(OR = 0.78,95% CI = 0.63 - 0.96,P = 0.021)。这一发现表明,MET中的这种种系变体可能会降低汉族人群患胃癌的易感性。