Polymorphisms and haplotypes of the miR-148/152 family are associated with the risk and clinicopathological features of gastric cancer in a Northern Chinese population.

Abstract

Our previous studies showed that the expressions of miR-148a, miR-152 and miR-148b are altered in gastric cancer (GC). The present study aimed to find relationship between individual single nucleotide polymorphisms (SNPs) or haplotypes of these miRNAs and susceptibility, clinicopathological parameters and prognosis of GC in a large sample of the Han population of Northern China. Twelve SNPs were genotyped using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry in a case-control study of 571 Chinese GC patients and 571 cancer-free controls. The rs11170877 G allele (P = 0.027) and the rs12231393 C allele (P = 0.034) were associated with a decreased risk of GC. However, these associations were lost after Bonferroni correction. The rs4719839 G allele was associated with Borrmann type III-IV GC (P = 0.034), increased tumour size (P = 0.020), an increased rate of lymph node metastasis (P = 0.047) and advanced TNM stage (P = 0.009). These associations were also lost after Bonferroni correction. The haplotype of miR-148b was significantly correlated with GC risk. The haplotypes in miRNA-148a were different in Borrmann types. The haplotype of miR-152 distributed various in the positive lymphovascular invasion group compared to negative group. Polymorphisms of miR-148b rs11170877 and 12231393 and their haplotypes were predictive factors of susceptibility to GC. A functional genetic variant of miRNA rs4719839 and the corresponding haplotype were associated with clinicopathological features and prognosis of advanced GCs.