Effect of Genetic Predisposition on the Risk of Gallbladder Cancer in Hungary

Abstract

A CYP1A1 polymorphism has been associated with an increased risk for gallbladder cancer (GBC) in Japanesewomen. However, genetic risk factors for GBC in Hungary, where the population has a relatively high GBCincidence, has not been well studied. We therefore tested associations between CYP1A1 T3801C, CYP1A1Ile462Val, GSTM1deletion, and TP53 Arg72Pro and GBC in Hungary. Genomic DNA was extracted fromperipheral blood of 100 controls (52 men and 48 women) and from the tissue embedded in paraffin of 43 cases (6men and 37 women). The case-control analysis was limited to females due to a small number of males. Of 37female cases, 21 (56.8%) were diagnosed as adenocarcinoma, and the remaining 16 (43.2%) were classified asnon-adenocarcinoma. The odds ratios (ORs) for the Ile/Val genotype and the Val allele were 8.9 (95% CI: 2.9-27.4) and 4.4 (95% CI: 1.7-11.1), respectively. The occurrence of the combined variant genotypes of CYP1A1Ile462Val and GSTM1 (37.8% vs. 8.3%) or CYP1A1 Ile462Val and TP53 Arg72Pro (24.3% vs. 0%) wassignificantly higher in the cases than in the controls. The Ile/Val genotype was significantly associated with anincreased risk of adenocarcinoma (OR 9.2; 95% CI: 2.6-32.6) and non-adenocarcinoma (OR 8.4; 95% CI: 2.2-32.4). Additionally, the Arg/Pro genotype increased risk of non-adenocarcinoma (OR 3.8; 95% CI: 1.2-12.8).The Val allele may contribute to the development of GBC not only in Japanese but also in Hungarian women.Our results provide a rationale for further studies of genetic variation on the risk of GBC in Hungary.