title: MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma.
abstract: BACKGROUND
  Micro 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.
  
  
  RESULTS
  A 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).
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yin-Hung
authors.initials: YH
authors.lastname: Chu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
authors.affiliation: Department of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan ; Department of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Liou
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Mennonite Christian Hospital, Hualien, Taiwan.
authors.forename: Chen-Chieh
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Department of Medicine, Armed-Force Taichung General Hospital, Taichung, Taiwan.
authors.forename: Wu-Hsien
authors.initials: WH
authors.lastname: Kuo
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects
chemical_list: C548683:MIRN499 microRNA, human; D035683:MicroRNAs