A p53 genetic polymorphism as a modulator of hepatocellular carcinoma riskin relation to chronic liver disease, familial tendency, and cigarette smoking in hepatitis B carriers

This study evaluated whether the codon 72 p53 polymorphism was related to h epatocellular carcinoma (HCC), Genotypes of p53 were determined in 80 incid ent cases of HCC and 328 controls nested in a cohort study of 4,841 male ch ronic hepatitis B carriers. No overall increase in HCC risk with the Pro va riant allele of the p53 polymorphism was apparent. However, there were syne rgistic effects on HCC development for the Pro allele with chronic liver di sease and family history of HCC in first-degree relatives. Compared with su bjects without the Pro allele and chronic liver disease, the increase in HC C risk associated with chronic liver disease among those without the Pro al lele was only threefold. Subjects with both chronic liver disease and the P ro allele were at an increased risk of 7.60 (95% CI = 2.28-25.31), When sub jects without family history of HCC and the Pro allele were considered as t he reference group, there was no apparent increased risk of HCC for those w ithout the Pro allele who had family history of HCC, Among those with both factors, there was a significantly increased risk of 3.29 (95% CI = 1.10-9. 85), Both cigarette smoking and glutathione S-transferase MI genotype modif ied the risk of HCC associated with the p53 polymorphism. Significantly inc reased risk associated with the p53 genotype was observed only among smoker s who were glutathione S-transferase-null (Pro/Pro vs. Arg/Arg: odds ratio = 6.46; 95% CI = 1.55-26.94), The p53 polymorphism also interacted with the cytochrome P450 1A1 and carotenoid levels in smoking-related hepatocarcino genesis.