Objective: Carcinogenic aromatic amines, derived from cooked meat, are activated or inactivated by hepatic N-acetyltransferase (NAT). The aim of this study was to evaluate the relationship of NAT2 genetic polymorphisms with hepatocellular carcinoma (HCC), with special reference to the interaction of dietary habits.
Methods: Peripheral white blood cell DNA from 185 HCC patients and 185 matched controls were genotyped for NAT2 by a polymerase chain reaction-restriction fragment length polymorphism method. All the subjects studied were chronic viral hepatitis B or C carriers with liver cirrhosis. Dietary habits of the subjects were assessed using a semiquantitative food frequency questionnaire.
Results: There was no association between the susceptibility of HCC and the overall NAT2 genotypes. However, in rapid acetylators (with two wild type NAT2*4 alleles), there was a trend of increased HCC risk from low to intermediate and high red meat intake (OR = 1, 2.66, 3.89; p(trend) = 0.016), even when adjusted for family history of HCC and habitual alcohol drinking. The interaction between red meat intake and the NAT2*4 acetylator status for an increased risk of HCC was significant (p = 0.007).
Conclusions: Polymorphisms of the NAT2 gene may confer different susceptibilities to the effect of red meat intake on HCC. In rapid acetylators with chronic viral hepatitis-related cirrhosis, red meat intake may play a role in hepatocarcinogenesis.