P0162 CYP1B1 polymorphisms and hepatocellular cancer risk in a chinese population

Abstract

Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as oestrogen metabolism. We hypothesised that genetic variants in CYP1B1 may modify individual susceptibility to hepatocellular carcinoma (HCC). Methods To test this hypothesis, we evaluated the associations of three CYP1B1 single nucleotide polymorphisms (SNPs) and HCC risk in a case-control study of 468 HCC cases and 515 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were done to detect these polymorphisms. Findings In overall analysis, the three SNPs rs10012, rs1056836, and rs1800440 were not significantly associated with HCC risk. However, we found that variant genotypes containing the G allele of rs1056836 were associated with a significantly increased risk of HCC among HbsAg-positive individuals (adjusted odds ratio 2.13, 95% confidence interval [CI] 1.18–3.86), but not among HbsAg-negative individuals in the subgroup analysis by HBV carrier status. When stratified by smoking status, we found that the variant GG genotype increased risk of HCC by 13.97-fold (95% CI 1.28–152.94) among smokers. Furthermore, a high risk for liver cirrhosis was noted in HCC patients with rs1056836 CG and GG genotypes compared with CC homozygotes. For the other two SNPs, we did not find any significant evidence of association with HCC risk in any subgroup. Interpretation Our results suggest that CYP1B1 rs1056836 polymorphism may be an important factor contributing to increased susceptibility and pathological development of HCC in a Chinese population. CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as oestrogen metabolism. We hypothesised that genetic variants in CYP1B1 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis, we evaluated the associations of three CYP1B1 single nucleotide polymorphisms (SNPs) and HCC risk in a case-control study of 468 HCC cases and 515 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were done to detect these polymorphisms. In overall analysis, the three SNPs rs10012, rs1056836, and rs1800440 were not significantly associated with HCC risk. However, we found that variant genotypes containing the G allele of rs1056836 were associated with a significantly increased risk of HCC among HbsAg-positive individuals (adjusted odds ratio 2.13, 95% confidence interval [CI] 1.18–3.86), but not among HbsAg-negative individuals in the subgroup analysis by HBV carrier status. When stratified by smoking status, we found that the variant GG genotype increased risk of HCC by 13.97-fold (95% CI 1.28–152.94) among smokers. Furthermore, a high risk for liver cirrhosis was noted in HCC patients with rs1056836 CG and GG genotypes compared with CC homozygotes. For the other two SNPs, we did not find any significant evidence of association with HCC risk in any subgroup. Our results suggest that CYP1B1 rs1056836 polymorphism may be an important factor contributing to increased susceptibility and pathological development of HCC in a Chinese population.