TY - JOUR
T1 - Hepatitis B infection is causally associated with extrahepatic cancers
T2 - A Mendelian randomization study
AU - Kamiza, Abram Bunya
AU - Fatumo, Segun
AU - Singini, Mwiza Gideon
AU - Yeh, Chih Ching
AU - Chikowore, Tinashe
N1 - Funding Information:
The study has been supported by the South African Medical Research Council (with funds received from the South African National Department of Health) and the UK Medical Research Council (with funds from the UK Government's Newton Fund) (MRC-RFA-SHIP 01–2015) for the Evolving Risk Factors for Cancers in African populations study (ERICA-SA). The funders stated therein had no role in the paper design, data collection, data analysis, interpretation and writing of the paper. TC is an international training fellow supported by the Wellcome Trust grant (214205/Z/18/Z). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the South African Medical Research Council or the South African National Department of Health or the UK Medical Research Council from the UK Government's Newton Fund.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/5
Y1 - 2022/5
N2 - Background: Evidence from observational studies suggests that chronic hepatitis B virus (HBV) infection is associated with extrahepatic cancers. However, the causal association between chronic HBV infection and extrahepatic cancers remains to be determined. Methods: We performed two-sample Mendelian randomization (MR) to investigate whether chronic HBV infection is causally associated with extrahepatic cancers. We identified four independent genetic variants strongly associated (P-value < 5 × 10−8) with the exposure, chronic HBV infection in 1371 cases and 2938 controls of East Asian ancestry in Korea, which were used as instrumental variables. Genome-wide association summary level data for outcome variables, that included cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, hepatocellular carcinoma, lung, ovary and pancreas were obtained from Biobank Japan. Findings: Using the multivariable inverse variance weighted method, we found genetic liability to chronic HBV infection causally associated with extrahepatic cancers including cervical cancer (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.29–1.91, P-value = 0.0001) and gastric cancer (OR = 1.12, 95% CI = 1.05–1.19, P-value = 0.0001). Moreover, chronic HBV infection (OR = 1.20, 95% CI = 1.07–1.34, P-value = 0.0021) was causally associated with hepatocellular carcinoma, supporting a well-established association between chronic HBV infection and hepatocellular carcinoma. Interpretation:: Our MR analysis revealed that chronic HBV infection is causally associated with extrahepatic cancers including cervical and gastric cancers. Funding: None.
AB - Background: Evidence from observational studies suggests that chronic hepatitis B virus (HBV) infection is associated with extrahepatic cancers. However, the causal association between chronic HBV infection and extrahepatic cancers remains to be determined. Methods: We performed two-sample Mendelian randomization (MR) to investigate whether chronic HBV infection is causally associated with extrahepatic cancers. We identified four independent genetic variants strongly associated (P-value < 5 × 10−8) with the exposure, chronic HBV infection in 1371 cases and 2938 controls of East Asian ancestry in Korea, which were used as instrumental variables. Genome-wide association summary level data for outcome variables, that included cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, hepatocellular carcinoma, lung, ovary and pancreas were obtained from Biobank Japan. Findings: Using the multivariable inverse variance weighted method, we found genetic liability to chronic HBV infection causally associated with extrahepatic cancers including cervical cancer (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.29–1.91, P-value = 0.0001) and gastric cancer (OR = 1.12, 95% CI = 1.05–1.19, P-value = 0.0001). Moreover, chronic HBV infection (OR = 1.20, 95% CI = 1.07–1.34, P-value = 0.0021) was causally associated with hepatocellular carcinoma, supporting a well-established association between chronic HBV infection and hepatocellular carcinoma. Interpretation:: Our MR analysis revealed that chronic HBV infection is causally associated with extrahepatic cancers including cervical and gastric cancers. Funding: None.
KW - Cancer
KW - Genetics
KW - HBV
KW - Mendelian randomization
KW - SNPs
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U2 - 10.1016/j.ebiom.2022.104003
DO - 10.1016/j.ebiom.2022.104003
M3 - Article
AN - SCOPUS:85128278684
SN - 2352-3964
VL - 79
JO - EBioMedicine
JF - EBioMedicine
M1 - 104003
ER -