The epidemiology of viral, environmental and genetic factors in hepatocellular carcinoma: A case-control study from the Gambia, West Africa

Hepatocellular carcinoma (HCC) is the most common and lethal cancer in The Gambia, West Africa. Hepatitis B virus (HBV) infection is transmitted horizontally in young childhood resulting in 15--20% of the population becoming chronic carriers. Hepatitis C virus (HCV) infection is uncommon but dietary exposure to aflatoxin is ubiquitous. Previous studies have not concurrently evaluated the role of HBV, HCV, 249 ser p53 mutations and genetic susceptibility to HCC nor have the effects of combined exposures to these viral, environmental and genetic factors been investigated.;Incident cases of HCC (n = 197) recruited from three tertiary hospitals in The Gambia were diagnosed by clinical and ultrasound criteria and serum alpha-fetoprotein >100 ng/ml. Controls (n = 405) without clinical evidence of liver disease were recruited from the outpatient clinics of the same hospital sites and frequency matched by age and sex. HBV surface (HBsAg) and "e" antigenemia (HBeAg) were determined as markers of chronic carriage and active replication, respectively. HCV status was determined by third generation ELISA with RIBA confirmation.;Our findings confirm a significant HCC risk with both HBV and HCV infections and provide evidence that dual infection results in an additive rather than a multiplicative effect. HCV-related HCC cases were much older than seen with HBV infection, consistent with differences in transmission of the two viruses, but the data were also suggestive of a possible HCV cohort effect. The association between 249 ser p53 mutations and HBeAg among cases raises the possibility of an interaction between HBV replication and the mutational effect of aflatoxin exposure. We examined a variety of genetic polymorphisms that may confer an increased risk for HCC and report novel findings of small increases in risk for HCC with the DNA repair enzyme XRCC1 and confirmatory evidence of HCC risk for HYL1 in an environment with high chronic viral hepatitis infections and environmental exposure to aflatoxin. Methodologically, we demonstrated the use of circulating cell-free DNA as a source of genetic material to examine "hotspot" p53 gene mutations associated with aflatoxin exposure. Identification of these mutations in healthy control participants raises the potential for clinical application of these techniques in identifying highly susceptible individuals appropriate for screening or early intervention. (Abstract shortened by UMI.).