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Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma.

ABSTRACT: We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values?

SUBMITTER: Sawai H

PROVIDER: S-EPMC5962604 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma.

Sawai Hiromi H Nishida Nao N Khor Seik-Soon SS Honda Masao M Sugiyama Masaya M Baba Natsumi N Yamada Kayoko K Sawada Norie N Tsugane Shoichiro S Koike Kazuhiko K Kondo Yuji Y Yatsuhashi Hiroshi H Nagaoka Shinya S Taketomi Akinobu A Fukai Moto M Kurosaki Masayuki M Izumi Namiki N Kang Jong-Hon JH Murata Kazumoto K Hino Keisuke K Nishina Sohji S Matsumoto Akihiro A Tanaka Eiji E Sakamoto Naoya N Ogawa Koji K Yamamoto Kazuhide K Tamori Akihiro A Yokosuka Osamu O Kanda Tatsuo T Kanda Tatsuo T Sakaida Isao I Itoh Yoshito Y Eguchi Yuichiro Y Oeda Satoshi S Mochida Satoshi S Yuen Man-Fung MF Seto Wai-Kay WK Poovorawan Yong Y Posuwan Nawarat N Mizokami Masashi M Tokunaga Katsushi K

Scientific reports 20180521 1

We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10<sup>-4</sup> located within the HLA class I region and three SNPs were genotyped in three independent pop ...[more]

PMID: 29784950

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Project description:Background & aimsAlthough HBV is a major cause of death in Africa, its genetic variability has been poorly documented. This study aimed to address whether HBV genotype and surface gene variants are associated with HBV-related liver disease in The Gambia.MethodsWe conducted a case-control study nested in the Prevention of Liver Fibrosis and Cancer in Africa programme. Consecutive treatment-naive patients with chronic HBV infection and detectable viral load were recruited: 211 controls with no significant liver disease and 91 cases (56 cirrhosis and 35 HCC cases). HBV genotypes and surface gene variants were determined by Sanger sequencing or next-generation sequencing (NGS) in serum DNA. Aflatoxin B1 (AFB1)-specific codon 249 TP53 mutation was determined by NGS in circulating cell-free plasma DNA.ResultsIn phylogenetic analysis, 85% of individuals carried HBV genotype E, 14% genotype A, and 1% A/E recombinant viruses. Surface gene variants were more frequently observed in cases (43% and 57% in cirrhosis and HCC cases, respectively) than controls (25%; p <0.001), with preS2 deletions between nucleotides 38-55 (preS2Δ38-55) being the main genetic variant detected. In multivariable analysis, HBeAg seropositivity, low HBsAg levels, and HDV seropositivity were significantly associated with cirrhosis and HCC, whilst older age, higher viral load, genotype A, preS2Δ38-55, and AFB1 exposure were only associated with HCC. There was a multiplicative joint effect of preS2Δ38-55 variants with HBeAg seropositivity (odds ratio [OR] 43.1 [10.4-177.7]), high viral load >2,000 IU/ml (OR 22.7 [8.0-64.9]), HBsAg levels <10,000 IU/ml (OR 19.0 [5.5-65.3]), and AFB1 exposure (OR 29.3 [3.7-230.4]) on HCC risk.ConclusionsThis study identified a hotspot for HBV preS2 deletions as a strong independent factor for HCC in The Gambia, with HBV genotypes and AFB1 exposure contributing to the high liver cancer risk.Lay summaryAlthough HBV-related liver disease is highly prevalent in sub-Saharan Africa, the associated virological characteristics are poorly studied. Using clinical data from African patients chronically infected with HBV, an assessment of the virological variability (genotypes and mutations) and exposure to AFB1, a toxin often contaminating food, was carried out. Our results show that HBV genotypes, the presence of a highly prevalent mutant form of HBV, and AFB1 exposure contribute to the high liver cancer risk in this population.

Dataset Information

Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma.

Publications

Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma.

Similar Datasets

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