Family history of liver cancer and hepatocellular carcinoma

Authors

  • Federica Turati,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
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  • Valeria Edefonti,

    1. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
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  • Renato Talamini,

    1. S.O.C. di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (Pordenone), Italy
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  • Monica Ferraroni,

    1. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
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  • Matteo Malvezzi,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
    3. Struttura Complessa di Statistica Medica, Biometria e Bioinformatica, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
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  • Francesca Bravi,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
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  • Silvia Franceschi,

    1. International Agency for Research on Cancer, Lyon, France
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  • Maurizio Montella,

    1. Unità di Epidemiologia, Istituto Tumori “Fondazione Pascale”, IRCCS, Naples, Italy
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  • Jerry Polesel,

    1. S.O.C. di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (Pordenone), Italy
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  • Antonella Zucchetto,

    1. S.O.C. di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (Pordenone), Italy
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  • Carlo La Vecchia,

    Corresponding author
    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
    3. International Prevention Research Institute (IPRI), Lyon, France
    • Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milan, Italy
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    • fax: +39 0233200231

  • Eva Negri,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
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  • Adriano Decarli

    1. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
    2. Struttura Complessa di Statistica Medica, Biometria e Bioinformatica, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
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  • Potential conflict of interest: Nothing to report.

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). 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 with an over 70-fold elevated HCC risk. (HEPATOLOGY 2011)

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