Genetic variation of CTNNB1 gene is associated with susceptibility and prognosis of gastric cancer in a Chinese population

摘要

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.