Department of Molecular & Genetic Toxicology, School of Public Health, Cancer Center of Nanjing Medical University, Nanjing, China.
Mutagenesis. 2012 Nov;27(6):623-30. doi: 10.1093/mutage/ges027. Epub 2012 Jul 30.
Gastric cancer is the second leading cause of cancer-related death worldwide with a low 5-year survival (S5y) after initial diagnosis. Although aberrant Wnt/β-catenin (CTNNB1) signaling has been observed in multiple human cancers, there is no information on the role of CTNNB1 polymorphisms in gastric cancer risk and S5y. We performed a genetic association study to analyse the correlation between the five tagged SNPs (tSNPs) (rs4135385, rs1798808, rs1880481, rs11564465 and rs2293303) of CTNNB1 and gastric cancer risk and survival. A total of 944 patients with complete follow-up information and 848 cancer-free controls were enrolled in this study. The rs1880481 polymorphism was correlated with decreased risk of gastric cancer [AC/AA vs. CC: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.63-0.91], whereas the three other SNPs showed opposite effect (AG/AA vs. GG: adjusted OR = 1.31, 95% CI = 1.08-1.57 for rs4135385; GG vs. AA/AG: 2.09, 1.02-4.28 for rs11564475; TT vs.
CC/CT: 4.87, 2.72-8.71 for rs2293303). We further investigated if these tSNPs were related to the S5y of gastric cancer, and the results displayed that only the SNP rs4135385 AG/AA genotypes were significantly associated with a favorable gastric cancer survival compared with the GG genotype [adjusted hazard ratio (HR) = 0.80, 95% CI = 0.66-0.97], and the association was more prominent among patients with non-cardia gastric cancer (NCGC) than those with cardia gastric cancer (CGC) (Log-rank P = 0.007 for NCGC and 0.417 for CGC). Our results indicated that the genetic variants of CTNNB1 could be used as predictors of gastric cancer susceptibility and prognosis.
胃癌是全球导致癌症相关死亡的第二大原因，初始诊断后的 5 年生存率（S5y）较低。虽然异常的 Wnt/β-连环蛋白（CTNNB1）信号已在多种人类癌症中观察到，但 CTNNB1 多态性与胃癌风险和 S5y 的关系尚无信息。我们进行了一项遗传关联研究，以分析 CTNNB1 的五个标记单核苷酸多态性（tSNP）（rs4135385、rs1798808、rs1880481、rs11564465 和 rs2293303）与胃癌风险和生存之间的相关性。共纳入 944 例具有完整随访信息的患者和 848 例无癌症对照者进行本研究。rs1880481 多态性与胃癌风险降低相关[AC/AA 与 CC：调整后的优势比（OR）=0.76，95%置信区间（CI）=0.63-0.91]，而其他三个 SNP 则显示出相反的作用（AG/AA 与 GG：rs4135385 的调整 OR=1.31，95%CI=1.08-1.57；GG 与 AA/AG：rs11564475 的 2.09，1.02-4.28；TT 与 CC/CT：rs2293303 的 4.87，2.72-8.71）。我们进一步研究了这些 tSNP 是否与胃癌的 S5y 相关，结果显示只有 SNP rs4135385 的 AG/AA 基因型与胃癌的良好生存显著相关，与 GG 基因型相比[调整后的风险比（HR）=0.80，95%CI=0.66-0.97]，并且在非贲门胃癌（NCGC）患者中比贲门胃癌（CGC）患者更明显（NCGC 的 Log-rank P=0.007，CGC 的 P=0.417）。我们的结果表明，CTNNB1 的遗传变异可作为胃癌易感性和预后的预测因子。
