Source Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; Dipartimento di Medicina del Lavoro, Università degli Studi di Milano, Milan, Italy.
Familial clustering of hepatocellular carcinoma (HCC) has been reported frequently among 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 (OR) and the corresponding 95% confidence intervals (CI) 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 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 to 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 9 case-control and 4 cohort studies, for a total of about 3600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03).
CONCLUSION: 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 to an over 70-fold elevated HCC risk.