Genetic Polymorphisms of TP53 and ApoB Genes and Risk of Biliary Tract Cancer: A Case–Cohort Study in Japan Available to Purchase

Although several retrospective studies have investigated the association of TP53 rs1042522 and ApoB rs693 with the risk of biliary tract cancer (BTC), results have been inconsistent. In this study, 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 HRs and 95% confidence intervals (CI) using a weighted Cox proportional hazards model. TP53 rs1042522 showed a statistically significant association with the 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 seemed to be associated with BTC risk in a recessive model, but not in a dominant model. On comparison of three BTC subtypes, TP53 rs1042522 seemed 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 nonsignificant 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 the TP53 rs1042522 polymorphism and the 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.

Prevention Relevance: This prospective study highlights the effect of TP53 rs1042522 on BTC risk in Japanese individuals. Identifying carriers of the high-risk CC genotype may facilitate targeted surveillance and early detection strategies, potentially reducing mortality and improving outcomes. Further large-scale studies are required to clarify environmental interactions and optimize prevention.