Abstract
BackgroundMicro RNAs (miRNAs) are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs) in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma.Methodology/Principal FindingsA total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a (rs2910164), miRNA149 (rs2292832), miRNA196 (rs11614913), and miRNA499 (rs3746444) genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88–4.30). In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52–8.70; AOR = 3.38, 95% CI = 1.68–6.80).ConclusionsThese results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the second leading cause of cancerrelated death in Taiwan
These results suggest that a significant association exists between miRNA499 Singlenucleotide polymorphisms (SNPs) and hepatocellular carcinoma
In addition to common risk factors such as hepatitis B and hepatitis C, recent studies have shown that gene mutations may influence the inflammation mechanism that contributes to cell differentiation, proliferation, and apoptosis and connects several diseases and cancers [1,2,3]
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the second leading cause of cancerrelated death in Taiwan. In addition to common risk factors such as hepatitis B and hepatitis C, recent studies have shown that gene mutations may influence the inflammation mechanism that contributes to cell differentiation, proliferation, and apoptosis and connects several diseases and cancers [1,2,3]. Viral mutations on the promoter region and preS region are significantly increased the risk of HCC. MiRNAs can target specific mRNAs and negatively regulate their translational efficiency and stability to control the downstream cellular process including proliferation, differentiation, and survival [6,7]. Based on the functions that regulate cell differentiation, proliferation, and survival, several studies have identified a relationship between miRNAs and cancer [10,11,12,13,14]. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma
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