title: Polymorphisms of a Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 and Aflatoxin B1-Related Hepatocellular Carcinoma.
abstract: BACKGROUND
  Altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is observed in hepatocellular carcinoma. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related hepatocellular carcinoma have not yet been elucidated.
  
  
  METHODS
  We conducted a hospital-based case-control study, including 1,706 hepatocellular carcinoma cases and 2,270 controls without any liver diseases or tumors, to assess the association between 74 polymorphisms in ADAMTS5 and AFB1-related hepatocellular carcinoma risk and prognosis. Genotype, mRNA levels, and TP53 gene mutation (TP53M) related to AFB1 exposure were tested using TaqMan-PCR or sequencing technique. ADAMTS5 protein level and microvessel density were analyzed by IHC.
  
  
  RESULTS
  Among these 74 polymorphisms, only rs2830581 affected hepatocellular carcinoma risk. Compared with the homozygote of rs2830581 G alleles (rs2830581-GG), the genotypes of rs2830581 A alleles (rs2830581-GA or -AA) increased hepatocellular carcinoma risk (OR: 1.85 and 4.40; 95% CI: 1.57-2.19 and 3.43-5.64, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Furthermore, the rs2830581 polymorphism modified the tumor recurrence-free survival and overall survival of patients. This polymorphism not only affected pathologic features of hepatocellular carcinoma such as tumor dedifferentiation and microvessel density, but also modified ADAMTS5 expression and the effects of transarterial chemoembolization treatment on hepatocellular carcinoma.
  
  
  CONCLUSIONS
  These results suggest ADAMTS5 polymorphisms may be risk and prognostic biomarkers of AFB1-related hepatocellular carcinoma, and rs2830581 is a potential candidate.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that ADAMTS5 rs2830581 polymorphism modifies AFB1-related hepatocellular carcinoma risk and prognosis.
authors.affiliation: Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities, 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, Baise, China.
authors.forename: Jin-Guang
authors.initials: JG
authors.lastname: Yao
authors.affiliation: Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, China.
authors.forename: Bing-Chen
authors.initials: BC
authors.lastname: Huang
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
authors.affiliation: Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, China. Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. stjulongxd@263.net.
authors.forename: Xi-Dai
authors.initials: XD
authors.lastname: Long
mesh_terms: D000071116:ADAMTS5 Protein / Q000235:genetics* / Q000378:metabolism*; D016604:Aflatoxin B1 / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D019483:Disintegrins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019699:Thrombospondins / Q000378:metabolism*
chemical_list: D019483:Disintegrins; D019699:Thrombospondins; D016604:Aflatoxin B1; D045726:Metalloproteases; D000071116:ADAMTS5 Protein