Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

Chan, Kelvin Yuen-Kwong; Wong, Chun–Ming; Kwan, Johnny S. H.; Lee, Joyce Man‐Fong; Cheung, Ka Wai; Yuen, Man Fung; Lai, Ching–Lung; Poon, Ronnie Tung‐Ping; Sham, Pak C.; Ng, Irene Oi–Lin

doi:10.1371/journal.pone.0028798

Cited by 60 publications

(52 citation statements)

References 28 publications

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“…16 This hypothesis-free approach based on linkage disequilibrium (LD) allows the discovery of novel genetic loci, which were previously not regarded to be associated with the trait. 17 Considering that the common genetic variants associated with serum IgG might be identified by the GWAS approach, we performed the present two-stage GWAS in a healthy Chinese male population. To the best of our knowledge, it is the first GWAS to search the population-specific genetic variations associated with serum IgG level.…”

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Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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IgG has a crucial role in humoral immune response. Serum IgG level is mainly determined under genetic control. To explore the genetic influence on serum IgG levels, a two-stage genome-wide association study (GWAS) was performed in a healthy Chinese population of 3495 men, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Three single-nucleotide polymorphisms (SNPs) located in TNFRSF13B on 17p11.2 or nearby were significantly associated with IgG level: rs4792800 in the intron (combined P-value ¼ 1.45 Â 10 À 12 ), rs12603708 in the intron (combined P-value ¼ 1.82 Â 10 À 8 ) and rs3751987 at B65 kb downstream of the 5 0 -UTR region of TNFRSF13B (combined P-value ¼ 3.67 Â 10 À 9 ). Additionally, smoking was identified to be associated with IgG level in both stages (Po0.001), but there was no significant interaction between smoking and the identified SNPs (P40.05). The strong association between variants at TNFRSF13B and IgG level may be helpful to further explore the biological mechanism by which the serum IgG is affected by transmembrane activator, calcium modulator and cyclophilin ligand interactor encoded by TNFRSF13B.Genes and Immunity (2012) 13, 509-513; doi:10.1038/gene.2012.26; published online 7 June 2012Keywords: IgG; genome-wide association studies; TNFRSF13B; TACI; smoking INTRODUCTION IgG, constituting some 80% of total serum immunoglobulin, is the most abundant class of antibodies (Ab) in serum and extracellular fluid. It has an important role in the defense against various pathogens, toxins and even cancers. 1 As the only isotype that can pass through the human placenta, IgG is able to protect the fetus in utero. 2 Meanwhile, IgG gets involved in chronic inflammatory processes contributed to the destruction of healthy tissues in autoimmune diseases, such as arthritis and systemic lupus erythematosus. 3 Serum IgG level varies considerably from one person to another, 4 but little when testing the same person repeatedly. 5 This variation in the serum IgG concentration reflects the balance among the rates of synthesis and catabolism. 6 Multitudinous environmental factors including infections, smoking and chemical compounds can contribute to this variation. 7-9 Reports of pedigree studies or twin studies 10,11 have shown that genetic factors are more important than environmental exposures in determining serum immunoglobulin level in human. 12,13 The values of genetic heritability was h 2 ¼ 0.617 þ 0.020 for IgG. 6 Besides, several studies in a population of common variable immunodeficiency patients or IgA deficiency patients implied that there might be an association between some gene loci and serum IgG level. 14,15 However, to the best of our knowledge, no study has ever been conducted to identify the immune loci directly involved in the regulation of the IgG level.Genome-wide association study (GWAS) is a powerful and unbiased tool for the identification of common genetic variants associated with complex traits. 16 This hypothesis-free approach base...

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Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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“…A GWAS study performed in HCV patients in Japan identified a polymorphism in MICA (gene involved in immune regulation) 30 whereas another study in the same population identified a different polymorphism in DEPDC5 (gene of unknown function) 31 , associated with HCC development. In Chinese patients infected by HBV, SNPs were identified in STAT4 (a key protein of the inflammatory pathway) 32 , TPTE2 (a homolog of PTEN) 33 , DCL1 (a tumor suppressor gene implicated in HCC pathogenesis) 34 , and in a region containing the UBEB4, KIF1B, PGD genes 35 were identified in 4 different studies as associated with HCC occurrence. All these polymorphisms require validation in patients with various etiologies and at different stages of the liver diseases 6 .…”

Section: Genetic Predisposition Environmental Factors and Mechanism mentioning

confidence: 99%

Genetic Landscape and Biomarkers of Hepatocellular Carcinoma

et al. 2015

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“…Genetic host factors are known to drive this association, with the identification of single nucleotide polymorphisms (SNPs). SNPs have been identified through genome wide association studies (GWAS): STAT4 (19), TPTE2 (20), CTLA-4 (21) and DCL1 (22) genes, as well as in the region containing the UBEB4, KIF1B and PGD genes (23). Additional SNPs have been described, but it is accepted that these identified SNPs only partially account for the variability in HCC susceptibility.…”

Section: Risk Factorsmentioning

confidence: 99%

Viral hepatitis and hepatocellular carcinoma: etiology and management

Zamor

deLemos

Russo

2017

J. Gastrointest. Oncol.

128

102

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Hepatitis B virus (HBV) risk and hepatocellular carcinoma (HCC) EpidemiologyIt is estimated that over 50% of HCC cases worldwide are related to chronic HBV (1,2). Since the implementation of worldwide HBV vaccination there has been an overall decline in the burden of HBV, yet the HBV burden remains quite high in various parts of the world. There are approximately 350-400 million people across the world infected with HBV, the majority reside in or originate from Asia. Each year HBV accounts for 749,000 new cases of HCC and 692,000 HCC-related deaths (3). The annual incidence of HCC is estimated to be <1% for non-cirrhotic HBV infected patients and 2-3% for those with cirrhosis. Because of worldwide and geographic variations in HBV incidence, the burden of HBV related HCC also varies. Asian-Pacific and sub-Saharan Africa represent the highest incidence of HCC worldwide. Much lower risk of HBV associated HCC is seen in the United States with less than 20% incidence. Due to its diversity, Europe has different areas: low risk (18%) in West and North and high risk (51%) East and South (4). Occult HBV or subclinical infection as defined by detectable HBV DNA in the liver but hepatitis B surface antigen (HBsAg) seronegativity is now recognized as increased risk for HCC. The risk is most notable in those over the age of 50 (5,6). Recently published data reveal that in China, the age-standardized death due to HBV-related HCC and cirrhosis in 2013 was 10.95 and 4.91 per 100,000 people (7). Fifty-five percent of all HCC cases worldwide are reported from China (8).In 1991, the WHO recommended the integration of the HBV vaccine into national immunization programs in countries with an HBV carrier prevalence of 8% or higher by 1995 and in all other countries by 1997 (9). The universal infant vaccination rate in sub-Saharan Africa was initially quite low at 5% in 2000 but increased to 72% by 2012. Parts of the Pacific region had the lowest immunization rates, but by 2012 had increased to the highest rates at 91%. Taiwan has an exceptionally higher This review outlines the various mechanisms and pathophysiology that contributes to this process. There will also be a review on the recommended screening for HCC. Treatment considerations, which are different for these viruses, will be outlined in this review.

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Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

Cited by 60 publications

References 28 publications

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Genetic Landscape and Biomarkers of Hepatocellular Carcinoma

Viral hepatitis and hepatocellular carcinoma: etiology and management

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