title: Potentially functional genetic variants in microRNA processing genes and risk of HBV-related hepatocellular carcinoma.
abstract: Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3'-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC.
authors.affiliation: Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China; Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jiaze
authors.initials: J
authors.lastname: An
authors.forename: Jibin
authors.initials: J
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhai
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Shandong
authors.initials: S
authors.lastname: Pan
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhining
authors.initials: Z
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D060565:Argonaute Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D043244:Ribonuclease III / Q000235:genetics*; D012307:Risk Factors; D020931:ran GTP-Binding Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; D035683:MicroRNAs; C421088:PIWIL1 protein, human; C120587:RAN protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020931:ran GTP-Binding Protein
keywords: DICER1; HCC; PIWIL1; RAN; SNP; miRNA