title: Family history of liver cancer and hepatocellular carcinoma.
abstract: Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti-hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random-effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta-analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03).
  
  
  CONCLUSIONS
  A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk.
authors.affiliation: Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Turati
authors.forename: Valeria
authors.initials: V
authors.lastname: Edefonti
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Monica
authors.initials: M
authors.lastname: Ferraroni
authors.forename: Matteo
authors.initials: M
authors.lastname: Malvezzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Bravi
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Montella
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.forename: Eva
authors.initials: E
authors.lastname: Negri
authors.forename: Adriano
authors.initials: A
authors.lastname: Decarli
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010375:Pedigree; D015995:Prevalence; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D016019:Survival Analysis