title: Polymorphisms in the precursor microRNAs and aflatoxin B1-related hepatocellular carcinoma.
abstract: The altered expression of some microRNAs (miRNAs) is observed in hepatocellular carcinoma (HCC); however, the genetic polymorphisms in the precursor miRNAs (pre-miRNAs) in aflatoxin B1 (AFB1)-related HCC have not yet been investigated. A hospital-based case-control study, including 1,706 HCC cases and 2,270 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area of China to assess the relationship between 48 polymorphisms in the pre-miRNAs and AFB1-related HCC risk and prognosis. Among 48 polymorphisms, only rs28599926 (in the miRNA 1268a) affected HCC risk. Compared with the homozygote of rs28599926C alleles (rs28599926-CC), the genotypes of rs28599926 T alleles (namely rs28599926-CT or -TT) increased HCC risk (odds ratio [OR]: 1.63 and 5.52, 95% confidence interval [CI]: 1.40-1.90 and 4.27-7.14, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. This polymorphism was associated not only with larger tumor size, higher portal vein tumor risk, and tumor dedifferentiation, but also with higher AFB1 adducts levels and increasing the mutation risk of TP53 gene. Furthermore, rs28599926 modified the tumor recurrence-free survival (hazard ratio [HR]: 2.86, 95% CI: 2.36-3.43) and overall survival (HR: 2.12, 95% CI: 1.86-2.41) of cases. Additionally, one target of miR-1268a was show to be the ADAMTS4 mRNA and rs28599926 polymorphism might modify ADAMTS4 expression. These findings indicate that polymorphisms in the pre-miRNAs may be risk and prognostic biomarkers of AFB1-related HCC, and rs28599926 in miR-1268a is such a potential candidate. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities (AHYMCN), Baise, China.|Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xi-Dai
authors.initials: XD
authors.lastname: Long
authors.affiliation: Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities (AHYMCN), Baise, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities (AHYMCN), Baise, China.
authors.forename: Jin-Guang
authors.initials: JG
authors.lastname: Yao
authors.affiliation: Department of Medicine, The Affiliated Hospital of Youjiang Medical College for Nationalities (AHYMCN), Baise, China.
authors.forename: Pinhu
authors.initials: P
authors.lastname: Liao
authors.affiliation: Department of Surgery, The Affiliated Hospital of Youjiang Medical College for Nationalities (AHYMCN), Baise, China.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Tang
authors.affiliation: Department of Pathology, The Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000071121:ADAMTS4 Protein / Q000235:genetics*; D016604:Aflatoxin B1 / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C000619243:MIRN1268 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human
keywords: aflatoxin B1; hepatocellular carcinoma; miR-1268a; polymorphism; pre-miRNA