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Division for Cancer Epidemiology, Danish Cancer Society, DK-2100 Copenhagen Ø, Denmark [J. H. O.]; Institut für Medizinische Biometrie und Informatik der Albert Ludwigs Universität Freiburg, D-79104 Freiburg, Germany [G. S.]; Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892 [J. D. B., L. B. T.]; Division of Pathology and Toxicology, American Health Foundation, Valhalla, New York 10595 [J. W., G. M. W.]; Department of Chemical Pathology, Armed Forces Institute of Pathology, Washington, DC [F. B. J.]; and Nuffield Department of Pathology and Bacteriology, John Radcliff Hospital, University of Oxford, Headington, Oxford OX3 9DU, United Kingdom [J. O. M.]
The possible influence of phenobarbital and phenytoin treatment on cancer risk was investigated in a case-control study nested in a cohort of 8004 epileptic patients in Denmark. Information on anticonvulsive treatments was abstracted for 95% of 60 patients with cancers of the liver and biliary tract or malignant lymphoma and for 94% of 171 cancer-free control patients. Use of anticonvulsive drugs was correlated with angiographic procedures that used Thorotrast, a well-known human liver carcinogen. After exclusion of study subjects exposed to Thorotrast, no association was seen between treatment with phenobarbital and cancer of the liver (odds ratio, 1.0; 95% confidence interval, 0.1–8.0) or biliary tract (odds ratio, 0.8; 95% confidence interval, 0.1–4.2). Furthermore, a histopathological evaluation of slides from 7 of 9 liver cancer patients not treated with Thorotrast revealed that 3 of the 4 cases of hepatocellular carcinoma involved cirrhosis of the liver, which suggested an etiological role for alcohol or viral hepatitis. A possible link was observed between use of phenytoin and risk for non-Hodgkin's lymphoma (1.8; 0.5–6.6), with a rising trend in risk with increasing dose. Our results suggest that the increased risk for cancers of the liver and biliary tract among Danish epileptic patients is likely to be due to Thorotrast administration and factors associated with cirrhosis of the liver rather than to anticonvulsive treatment.
1 To whom requests for reprints should be addressed.
Received 8/18/94. Accepted 11/ 8/94.
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