title: Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study.
abstract: OBJECTIVE
  Chronic hepatitis C virus (HCV) infection is a well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV.
  
  
  METHODS
  A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 88 single nucleotide polymorphisms (SNPs) in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied odds ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and recurrence of HCC were analyzed.
  
  
  RESULTS
  Six SNPs associated with risk of HCC were identified (OR range: 0.29-1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19-fold higher relative OR compared with the lowest risk group (P = 1.08 × 10(-5)). Predicted 10-year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence-free survival of radiofrequency ablation-treated HCC in the high risk group (n = 53) was lower than that of low risk group (n = 58, P = 0.038).
  
  
  CONCLUSIONS
  Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV.
authors: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama city, Japan. tomotake79@yahoo.co.jp
authors: Takeshi
authors: T
authors: Tomoda
authors: Kazuhiro
authors: K
authors: Nouso
authors: Akiko
authors: A
authors: Sakai
authors: Mamoru
authors: M
authors: Ouchida
authors: Sayo
authors: S
authors: Kobayashi
authors: Koji
authors: K
authors: Miyahara
authors: Hideki
authors: H
authors: Onishi
authors: Shinichiro
authors: S
authors: Nakamura
authors: Kazuhide
authors: K
authors: Yamamoto
authors: Kenji
authors: K
authors: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000601:surgery; D016022:Case-Control Studies; D017115:Catheter Ablation; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D056742:Cyclin D2 / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000235:genetics* / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D055815:Young Adult
chemical_list: C080336:CCND2 protein, human; C524694:CEP164 protein, human; D056742:Cyclin D2; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008868:Microtubule Proteins; C513287:RAD23B protein, human; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D045643:DNA Repair Enzymes