Abstract
BackgroundInflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship.MethodsMeta-analysis was performed on the associations between the miR-146a rs2910164 C > G and miR-499 rs3746444 T > C polymorphisms and hepatocellular carcinoma, using: allele contrast, dominant, and recessive models. A total of 12 studies(8 on miR-146a rs2910164 and 4 on miR-499 rs3746444) with three populations (Chinese, Korean, Turkish) were included in this study.ResultsResults show that both allele frequency and genotype distributions of miR-146a rs2910164 polymorphism are significantly associated with susceptibility to HCC (G versus C: OR = 1.153, 95% CI 1.083–1.228, P < 0.001; GC versus CC: OR = 1.165, 95% CI 1.054–1.286, P = 0.003; GG versus CC: OR = 1.361, 95% CI 1.192–1.553, P < 0.001; GG/GC versus CC: OR = 1.213, 95% CI 1.104–1.333, P < 0.001; GG versus GC/CC: OR = 1.210, 95% CI 1.080–1.356, P < 0.001). Our data suggest that people with G allele have a higher susceptibility to HCC as compared to those with C allele. However, meta-analysis failed to detect associations between miR-499 rs3746444 and HCC risk under each genetic model tested. Subgroup analysis showed that Chinese population with CC genotype are more vulnerable to HCC (OR = 2.171, 95% CI = 1.149–4.104, P = 0.017) than those with TT genotype.ConclusionsWe conclude that rs2910164 in miR-146a may confer susceptibility to HCC, especially in the Chinese population. No significant association was found between miR-499 rs3746444 and HCC, but subgroup study showed that subjects with CC genotype are more vulnerable to HCC than TT genotype in the Chinese population.
Highlights
Inflammation is a response of body tissues to injury or irritation
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations associated with population diversity, disease susceptibility, and individual response of medicine [10]
Identification of eligible studies We carried out a computer-based search of the most commonly used database, including PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), China Biological Medicine Database (CBMD) and VIP (Chinese) to identify all studies examining the relationship between miR-146a rs2910164, miR-499 rs3746444and hepatocellular carcinoma (HCC)
Summary
Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. Studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third most common cause of cancer-related mortality worldwide [1], especially in China. Growing evidence suggests that miRNAs regulate a wide range of biological processes, including development, cell differentiation, inflammation, proliferation, and apoptosis [7], and they even play a crucial role in initiating human cancers [8]. Dysregulated miRNAs, which otherwise function as suppressors of tumors or ontogenesis, may be responsible for the initiation, progression, and treatment outcomes of various forms of cancer [9]. Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations associated with population diversity, disease susceptibility, and individual response of medicine [10]
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