Published in Cancer Detection and Prevention 1998; 22(Supplement 1).

Increased incidence of hepatocellular carcinoma (HCC) in acute intermittent porphyria (AIP): Epidemiology and etiologic aspects

C Andersson MD PhD 1, L Bjersing MD PhD 2, F Lithner MD PhD 3

1 Primary Health Care Centre, Arjeplog, Departments of 2 Pathology and 3 Medicine, University Hospital, Umeå, Sweden.

AIM: To assess the prevalence of HCC in patients with AIP and to elucidate the carcinogenesis. METHODS: A population-based mortality study, of all inhabitants who died 1978-1990 (2122) in two northern municipalities with high prevalence of AIP (0,5-2%). Paraffin-embedded specimens of HCC were available for histopathological/molecular genetic examinations from 17 AIP-cases from northern Sweden. Several methods were used for screening relevant mutations in the p53 and H-ras genes. The tumours were analyzed for hepatitis B virus (HBV) DNA and for mutation in the porphobilinogen deaminase (PBGD) gene. RESULTS: Nine (27%) of the 33 patients with AIP (m/w 3/6) had HCC, as had 5/2089 (0.2%) patients not having AIP (m/w 3/2), p<0.0001. Mean age of death for AIP-patients with HCC was 69 yr (59-80). Precirrhosis-cirrhosis was common. No traces of hepatitis B DNA were found. The PBGD gene didn’t act as a tumour suppressor gene. None of the tumours had the selective mutations in the p53 gene which have been reported from countries with high exposure of aflatoxin and HBV. CONCLUSIONS: Patients with AIP are a new high risk group for developing HCC (25%). Liver precirrhosis-cirrhosis might be a preliminary stage to HCC. In AIP the disturbance in the heme synthesis compromises the oxidative defense. It also leads to intrinsic production of mutagene substances. A permanent system overload of oxidative stress may incite carcinogenic mutations in the liver. Screening for HCC is recommended all AIP patients aged >55 as early resection of a small HCC may be curative.

KEY WORDS: acute intermittent porphyria, hepatocellular carcinoma, liver cirrhosis, liver cirrhosis, oxidative stress, pathogenesis, .

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Paper presented at the International Symposium on the Impact of Biotechnology on Prediction, Prevention and Treatment of Cancer; Nice, France; October 24 - 27, 1998; in the section on Risk Identification.