Dataset Information

Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.

ABSTRACT:

Background and aim

Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS).

Methods

Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies.

Results

In this GWAS, we found that two SNPs were associated with HCC at P < 5E-8 and six SNPs at P < 5E-6 after adjusting for age, sex, and the top three principal components (PCs). Five of the SNPs in chromosome 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and rs4823173) and two in SAMM50 (rs3761472, rs3827385), were replicated in a small US case-control study and a cohort study in Singapore. The associations remained significant after adjusting for body mass index and HCV infection. Meta-analysis of multiple datasets indicated that these SNPs were significantly associated with HCC.

Conclusions

SNPs in PNPLA3 and SAMM50 are known risk loci for nonalcoholic fatty liver disease (NAFLD) and are suspected to be associated with HCC. Our GWAS demonstrated the associations of these SNPs with HCC in a US population. Biological mechanisms underlying the relationship remain to be elucidated.

SUBMITTER: Wang Z

PROVIDER: S-EPMC8674550 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.

Wang Zhanwei Z Budhu Anuradha S AS Shen Yi Y Wong Linda Lou LL Hernandez Brenda Y BY Tiirikainen Maarit M Ma Xiaomei X Irwin Melinda L ML Lu Lingeng L Zhao Hongyu H Lim Joseph K JK Taddei Tamar T Mishra Lopa L Pawlish Karen K Stroup Antoinette A Brown Robert R Nguyen Mindie H MH Koshiol Jill J Hernandez Maria O MO Forgues Marshonna M Yang Hwai-I HI Lee Mei-Hsuan MH Huang Yu-Han YH Iwasaki Motoki M Goto Atsushi A Suzuki Shiori S Matsuda Koichi K Tanikawa Chizu C Kamatani Yoichiro Y Mann Dean D Guarnera Maria M Shetty Kirti K Thomas Claire E CE Yuan Jian-Min JM Khor Chiea Chuen CC Koh Woon-Puay WP Risch Harvey H Wang Xin Wei XW Yu Herbert H

JGH open : an open access journal of gastroenterology and hepatology 20211127 12

<h4>Background and aim</h4>Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS).<h4>Methods</h4>Two case-control studies o ...[more]

PMID: 34950780

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Dataset Information

Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.

Background and aim

Methods

Results

Conclusions

Publications

Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.

Similar Datasets

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