A Meta-Analysis of miR-499 rs3746444 Polymorphism for Cancer Risk of Different Systems: Evidence From 65 Case-Control Studies

Abstract

MicroRNAs (miRNAs) are a class of endogenous, short and non-coding RNAs that may play important roles in the pathogenesis of tumor. The associations between microRNA-499 rs3746444 polymorphism and cancer risk in different systems remain inconclusive. This article is aimed to obtain more exact estimation of these relationships through a meta-analysis based on 52,456 individuals. We retrieved relevant and eligible studies from Pubmed and Embase database up to January 10, 2018. ORs and 95% CIs were used to estimate the associations between miR-499 polymorphism and cancer susceptibility in different systems. All analyses were performed using the Stata 11.0 software. A total of 65 case-control studies were retrieved using explicit inclusion and exclusion criteria. The study included 23,762 cases and 28,694 controls. Overall cancer analysis showed the association between miR-499 polymorphism and susceptibility to cancer was significant. MicroRNA-499 rs3746444 was found to be significantly associated with increased risk of cancer of the respiratory system (CC vs. TT: OR = 1.575, 95% CI = 1.268–1.955, CC vs. TC+TT: OR = 1.527, 95% CI = 1.232–1.892), digestive system (CC vs. TT: OR = 1.153, 95% CI = 1.027–1.295; TC vs. TT: OR = 1.109, 95% CI = 1.046–1.176; CC+TC vs. TT: OR = 1.112, 95% CI = 1.018–1.216; CC vs. TC+TT: OR = 1.137, 95% CI = 1.016–1.272; C vs. T: OR = 1.112, 95% CI = 1.025–1.206), urinary system (TC vs. TT: OR = 1.307, 95% CI = 1.130–1.512; CC+TC vs. TT: OR = 1.259, 95% CI = 1.097–1.446; C vs. T: OR = 1.132, 95% CI = 1.014–1.264), and gynecological system (C vs. T: OR = 1.169, 95% CI = 1.002–1.364). In the subgroup analysis by ethnicity, the result showed that significant association with an increased cancer risk was found in Asian. Subgroup analysis based on type of tumor was also performed, miR-499 rs3746444 is associated with susceptibility of cervical squamous cell carcinoma, lung cancer, prostate cancer, and hepatocellular carcinoma.

Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

“…Polymorphisms within microRNA genes may have an impact on an individual's susceptibility to cancer. The MIR499A rs3746444 polymorphism, for example, has been shown to be significantly associated with risk of cancer of the respiratory, digestive, urinary and gynecological systems 34 . Over the past decade, a growing number of studies have examined the association between MIR499A rs3746444 polymorphism and breast cancer susceptibility, but the results were inconsistent and often contradictory.…”

Potential Impact of MicroRNA Gene Polymorphisms in the Pathogenesis of Diabetes and Atherosclerotic Cardiovascular Disease

“…The role of inflammatory cytokines in cardiovascular disease is well established [116]. MiR-499 polymorphism (rs3746444) has also been reported to be associated with cancers [117] and autoimmune diseases [118].…”

<p>Association of miRNA-499 rs3746444 A>G variants with adenocarcinoma of esophagogastric junction (AEG) risk and lymph node status</p>

“…Accumulating evidence suggests a vital role for heredity in determining potential risk for malignancy. Yang et al recently performed a meta-analysis and identified the relationship between miRNA-499 rs3746444 A>G variants and risk to overall cancer was significant involving 23,762 cases and 28,694 controls 18. In addition, this study reported that miRNA-499 rs3746444 A>G variants also have been implicated in the risk of digestive system cancer.…”

“…The miRNA-499 rs3746444 A>G polymorphism was also associated with overall survival and progression-free survival among cases of neoadjuvant chemotherapy 16. A meta-analysis indicated that miRNA-499 rs3746444 variants were risk factors for overall cancer development 17,18. However, the correlation of miRNA-499 rs3746444 A>G variants with the susceptibility of AEG remains unclear.…”