Genetic polymorphisms of TP53 and ApoB genes and risk of biliary tract cancer: A case-cohort study in Japan.

Although several retrospective studies have investigated the association of TP53 rs1042522 and ApoB rs693 with risk of biliary tract cancer (BTC), results have been inconsistent. Here, to provide evidence from a prospective study, we analyzed the association of these two genetic polymorphisms with BTC risk using data from the Japan Public Health Center-based Prospective Study. We conducted a case-cohort study with 152 BTC cases and 12,159 subcohort subjects, and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using a weighted Cox proportional hazards model. TP53 rs1042522 showed a statistically significant association with risk of BTC (HR, 1.89; 95% CI, 1.27-2.82, in the recessive genetic model), whereas ApoB rs693 showed no apparent association. Of interest, TP53 rs1042522 appeared to be associated with BTC risk in a recessive model, but not in a dominant model. On comparison of three BTC subtypes, TP53 rs1042522 appeared to be associated with the incidence of gallbladder cancer and extrahepatic bile duct cancer (HR, 2.21; 95% CI, 1.14-4.28; and HR, 1.97; 95% CI, 1.00-3.88, respectively), but showed only a non-significant association with intrahepatic bile duct cancer (HR, 1.58; 95% CI, 0.63-3.96). In this prospective case-cohort study, we found evidence to support an association between TP53 rs1042522 polymorphism and risk of BTC. The null finding for ApoB rs693 might be due to the extremely low T allele frequency (4.4%) in the study population.