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HEPATOBILIARY |
1 Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden, and Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
2 Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden
Correspondence to:
Correspondence to:
K Hemminki, CNT Novum, 141 57, Sweden;
kari.hemminki{at}cnt.ki.se
ABSTRACT
Background and aims: Familial risks in liver and biliary cancers have been assessed in small case control studies, usually based on reported, but not medically verified, cancers in family members. Thus the degree of familial clustering for these cancers remains to be established.
Methods: The nationwide Swedish Family-Cancer Database was used, covering 10.2 million individuals for the years 1961–1998 from the Swedish Cancer Registry. Liver and biliary tract cancers were identified from 1121 offspring between the ages of 0 and 66 years and 17 131 parents. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for cancers in family members.
Results: All cancers in the liver and biliary system showed a familial SIR of 1.65 (95% CI 1.05–2.46). This was mainly explained by a high risk for familial gall bladder cancer (SIR 5.21 (95% CI 2.07–10.80)) and for familial primary liver cancer with hepatocellular carcinoma histology (SIR 4.69 (95% CI 1.48–11.04)). For gall bladder and hepatocellular cancer, maternal transmission appeared to be favoured. Gall bladder cancer was associated with pancreatic cancer (SIR 2.39 (95% CI 1.23–4.18)). Primary liver cancer was associated with cervical, urinary bladder, and endocrine gland tumours. Cancer in extrahepatic bile ducts was associated with ovarian cancer and that in ampulla of Vater with thyroid cancer; however, these associations may have been fortuitous.
Conclusions: This study has provided the first data on familial clustering of liver and gall bladder cancers, based on medically confirmed records. The risks were so high that heritable factors were likely to contribute, possibly modified by environmental factors. The demonstration of candidate genes would help to further characterise the familial risks.
Keywords: hepatocellular carcinoma; biliary tract; adenocarcinoma; pancreatic cancer; heritability
Abbreviations: HNPCC, hereditary non-polyposis colorectal cancer; SIR, standardised incidence ratio; SNOMED, Systematised Nomenclature of Medicine
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