Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus

A case control study

Takeshi Tomoda, Kazuhiro Nouso, Akiko Sakai, Mamoru Oouchida, Sayo Kobayashi, Koji Miyahara, Hideki Ohnishi, Shinichiro Nakamura, Kazuhide Yamamoto, Kenji Shimizu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Backgroud and Aim: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume27
Issue number4
DOIs
Publication statusPublished - 2012

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Hepacivirus
Case-Control Studies
Hepatocellular Carcinoma
Single Nucleotide Polymorphism
Recurrence
Odds Ratio
Chronic Hepatitis C
Virus Diseases
Genes
Fibrosis
Survival

Keywords

  • Chronic hepatitis C
  • Hepatocellular carcinoma
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus : A case control study. / Tomoda, Takeshi; Nouso, Kazuhiro; Sakai, Akiko; Oouchida, Mamoru; Kobayashi, Sayo; Miyahara, Koji; Ohnishi, Hideki; Nakamura, Shinichiro; Yamamoto, Kazuhide; Shimizu, Kenji.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 27, No. 4, 2012, p. 797-804.

Research output: Contribution to journalArticle

Tomoda, Takeshi ; Nouso, Kazuhiro ; Sakai, Akiko ; Oouchida, Mamoru ; Kobayashi, Sayo ; Miyahara, Koji ; Ohnishi, Hideki ; Nakamura, Shinichiro ; Yamamoto, Kazuhide ; Shimizu, Kenji. / Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus : A case control study. In: Journal of Gastroenterology and Hepatology (Australia). 2012 ; Vol. 27, No. 4. pp. 797-804.
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abstract = "Backgroud and Aim: 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). Conclusion: 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.",
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T1 - Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus

T2 - A case control study

AU - Tomoda, Takeshi

AU - Nouso, Kazuhiro

AU - Sakai, Akiko

AU - Oouchida, Mamoru

AU - Kobayashi, Sayo

AU - Miyahara, Koji

AU - Ohnishi, Hideki

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AU - Yamamoto, Kazuhide

AU - Shimizu, Kenji

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AB - Backgroud and Aim: 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). Conclusion: 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.

KW - Chronic hepatitis C

KW - Hepatocellular carcinoma

KW - Single nucleotide polymorphism

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