title: Birth order, as a proxy for age at infection, in the etiology of hepatocellular carcinoma.
abstract: First-born and second-born children are exposed to common infections after enrollment at school, whereas later-born children are exposed to these infections earlier through their older siblings. We have evaluated whether birth order is a risk factor for hepatitis B virus (HBV)-related, hepatitis C virus (HCV)-related, and apparently virus-unrelated hepatocellular carcinoma (HCC) in a large case-control study that included 333 HCC cases and 632 controls. In comparison with controls who were carriers of hepatitis B surface antigen (HBsAg), HBsAg-positive HCC cases were more likely to have been later-born children (odds ratio per increase in birth order = 2.0; 95% confidence interval = 1.2-3.6). There was no such evidence for anti-HCV-positive cases compared with anti-HCV-positive controls or for virus-negative HCC cases compared with virus-negative controls. We conclude that early infection with HBV increases the risk of HBV carriers to develop HCC, over and beyond its role in facilitating the establishment of a carrier state.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kuper
authors.forename: C
authors.initials: C
authors.lastname: Hsieh
authors.forename: S O
authors.initials: SO
authors.lastname: Stuver
authors.forename: L A
authors.initials: LA
authors.lastname: Mucci
authors.forename: A
authors.initials: A
authors.lastname: Tzonou
authors.forename: X
authors.initials: X
authors.lastname: Zavitsanos
authors.forename: P
authors.initials: P
authors.lastname: Lagiou
authors.forename: D
authors.initials: D
authors.lastname: Trichopoulos
mesh_terms: D000368:Aged; D000428:Alcohol Drinking; D001722:Birth Order; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D002353:Carrier State; D016022:Case-Control Studies; D005260:Female; D006115:Greece / Q000453:epidemiology; D016174:Hepacivirus / Q000302:isolation & purification*; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012907:Smoking; D011795:Surveys and Questionnaires