Effects of Common Polymorphism rs11614913 in Hsa-miR-196a2 on Lung Cancer Risk

<div><p>Background</p><p>Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the pathogenesis of lung cancer by altering the expression of tumor-related microRNAs. Several studies were investigated in recent years to evaluate the association between hsa-miR-196a2 rs11614913 polymorphism and increased/decreased lung cancer risk. In the present study, we performed a meta-analysis to systematically summarize the possible association.</p><p>Methodology/Principal Findings</p><p>We performed a meta-analysis of 4 case-control studies that included 2219 lung-cancer cases and 2232 cancer-free controls. We evaluated the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In the overall analysis, it was found that the rs11614913 polymorphism significantly elevated the risk of lung cancer (CC versus (vs.) TT OR = 1.26, 95% CI 1.07–1.49, P = 0.007; CC/CT vs. TT: OR = 1.13, 95% CI 0.98–1.29, P = 0.007; C vs. T: OR = 1.12, 95% CI 1.03–1.22, P = 0.008). In the subgroup analysis by ethnicity, statistically significantly increased cancer risk was found among Asians (CC vs. TT: OR = 1.30, 95% CI 1.10–1.54, P = 0.003; CT vs. TT: OR = 1.16, 95% CI 1.01–1.34, P = 0.039; CC vs. CT/TT: OR = 1.21, 95% CI 1.04–1.41, P = 0.012; C vs. T: OR = 1.14, 95% CI 1.05–1.25, P = 0.002). For Europeans, a significant association with lung cancer risk was found in recessive model (CC vs. CT/TT: OR = 0.63, 95% CI 0.40–0.98, P = 0.040). No publication bias was found in this study.</p><p>Conclusions/Significance</p><p>Our meta-analysis suggests that the rs11614913 polymorphism is significant associated with the increased risk of lung cancer, especially in Asians. Besides, the C allele of rs11614913 polymorphism may contribute to increased lung cancer risk.</p></div

Forest plots of the association between lung cancer risk and hsa-miR-196a2 rs11614913 polymorphism under homozygote comparison (CC vs. TT) in different ethnicity.

<p>OR: odds ratio; CI: confidence interval; I-squared, measure to quantify the degree of heterogeneity in meta-analyses. The squares and horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the study specific weight. The diamond represents the pooled OR and 95% CI.</p

Meta-analysis of hsa-miR-196a2 rs11614913 polymorphism and lung cancer risk.

<p>N, number of comparisons; OR, odds ratio; CI, confidence interval; vs., versus; CC vs. TT: Homozygote comparison; CT vs. TT: Heterozygote comparison; CC/CT vs. TT: Dominant model; CC vs. CT/TT: Recessive model; C vs. T: Allele comparison; R, random effect model; F, fixed effect model; Random effect model was chosen when P-value <0.10 and/or I²>50% for heterogeneity test; otherwise fixed effect model was used.</p

Forest plots of the association between lung cancer risk and hsa-miR-196a2 rs11614913 polymorphism under homozygote comparison (CC vs. TT).

<p>OR: odds ratio; CI: confidence interval; I-squared, measure to quantify the degree of heterogeneity in meta-analyses. The squares and horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the study specific weight. The diamond represents the pooled OR and 95% CI.</p

Begg’s funnel plot for publication bias test.

<p>OR: odds ratio; Log OR is plotted versus standard error of Log OR for each enrolled study. Horizontal line stands for mean effect size. Each circle point represents a separate study for the indicated association between hsa-miR-196a2 rs11614913 polymorphism and lung cancer risk by homozygote comparison (CC vs. TT).</p

Flow diagram of study identification with criteria for inclusion and exclusion in the meta-analysis.

<p>Flow diagram of study identification with criteria for inclusion and exclusion in the meta-analysis.</p

Characteristics of eligible studies included in the meta-analysis.

*<p>Hardy-Weinberg equilibrium (HWE) was evaluated using the goodness-of-fit chi-square test. P values were presented. P<0.05 was considered representative of a departure from HWE. PCR-RFLP was polymerase chain reaction-restriction fragment length polymorphism. PCR-HRMA was PCR-high-resolution melting analysis.</p