A functional polymorphism in MIR196A2 is associated with risk and prognosis of gastric cancer

Abstract

Genetic variations in miRNAs have been demonstrated to be capable of altering miRNA expression, consequently affecting many cancer-related biological processes. The MIR196A2 rs11614913 (T > C) polymorphism has been reported to be associated with various cancers development and progression. In our study, we aim to explore whether this polymorphism is relevant to the genetic susceptibility and prognosis of gastric cancer in a Chinese population. We analyzed the correlations of rs11614913 polymorphism with gastric cancer susceptibility in test and validation sets. The test set comprised 749 cases and 900 controls, while the validation set enrolled 940 cases and 1046 controls. Moreover, we evaluated the association between the polymorphism and gastric cancer prognosis in the validation set with follow-up information. The variant rs11614913 CC genotype was associated with a significantly reduced risk of gastric cancer in both sets (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62-0.99 for the test set and 0.64, 0.52-0.80 for the validation set) compared with the CT/TT genotypes. Furthermore, the CC genotype was associated with a significantly increased survival of gastric cancer compared with the CT/TT genotypes (adjusted hazard ratio [HR] = 0.72, 95% CI = 0.55-0.95), and the association was more prominent among patients with non-cardia gastric cancer than those with cardia gastric cancer (adjusted HR = 0.57, 95% CI = 0.40-0.83 for NCGC and 1.00, 0.65-1.53 for CGC). Our results suggested that the genetic variation of MIR196A2 may play a role in gastric cancer tumorigenesis.

Association between five common polymorphisms in microRNA genes and the risk of gastric cancer: a meta-analysis

“…However, according to our meta-analysis, no association could be identified between the miR-196a-2 C>T polymorphism and GC risk, and we observed no difference between groups upon stratification by ethnicity or source of control. These results contradict the findings of Wang et al (2013b), Dikeakos et al (2014), Kupcinskas et al (2014); this inconsistency might be due to the larger sample size of the current study. On the other hand, our results do not necessarily obviate the possibility that other polymorphic variants in miR-196a might be associated with GC susceptibility.…”

“…According to the inclusion criteria, 49 articles were excluded. Eventually, 19 case-control studies from 16 articles (Okubo et al, 2010;Peng et al, 2010;Sun et al, 2010;Zeng et al, 2010;Hishida et al, 2011;Ahn et al, 2012;Ma and Zheng, 2012;Zhang et al, 2012b;Zhou et al, 2012a,b;Wang et al, 2013b;Wu et al, 2013b;Yang et al, 2014;Dikeakos et al, 2014;Kupcinskas et al, 2014;Pu et al, 2014) were included in our meta-analysis, with 8285 patients and 10,716 controls in total. The details of the selection process are presented in Figure 1.…”

Lack of association of two common polymorphisms rs2910164 and rs11614913 with susceptibility to gastric cancer: A meta-analysis

“…Our comprehensive literature search yielded eight case-controlled studies (8)(9)(10)(11)(12)(13)(14)(15) that met the inclusion criteria, as described above ( Figure 1). The selected studies are of acceptable qualities for our meta-analysis, and we have summarized the characteristics of the chosen studies in Table 1.…”

“…Thus, we extracted the data for each SNP separately for this meta-analysis. Wang et al (15) presented ORs separately according to the different subgroups. Therefore, we included a total of six studies (8)(9)(10)(11)(12)14) involving 3.658 cases and 5.036 controls for rs2910164 and five studies (9,(13)(14)(15) including 2.915 cases and 3.303 controls for rs11614913 in our meta-analysis (Figure 1).…”

“…To date, several groups have demonstrated that the SNPs miR-146 rs2910164 and miR-196a2 rs11614913 are closely correlated with susceptibility to human gastric cancer (8)(9)(10)(11)(12)(13)(14)(15). However, the relationship between these two SNPs and susceptibility to the development of human gastric cancer are still inconclusive in the literature, probably resulting from the small sample size of an individual study.…”