Abstract / Summary
Background: Accumulating evidence suggests that vitamin D may influence cancer prognosis. We aimed to explore whether the TP53 codon 72 polymorphism (p.Pro72Arg; rs1042522) may be associated with differential effects of vitamin D supplementation on digestive tract cancer prognosis. Methods: This post hoc analysis of the AMATERASU randomized controlled trial included patients in whom both germline TP53 codon 72 genotype and p53 immunohistochemistry (IHC) assessment were available. Patients were stratified according to TP53 codon 72 genotype and p53 IHC expression. The association between vitamin D supplementation and relapse-free survival (RFS) was evaluated using Cox proportional hazards regression models within each subgroup. Results: A total of 333 participants (79.9%) out of 417 in the AMATERASU trial were included in the analysis. RFS was comparable between the vitamin D and placebo groups across the TP53 codon 72 genotype subgroups. The vitamin D group was significantly associated with more favorable RFS compared with the placebo group in patients with both the Arg/Arg genotype and high p53 IHC expression (HR, 0.32; 95% CI, 0.12–0.87; p = 0.03). However, with a fragility index of 2 and a non-significant three-way interaction among vitamin D supplementation, p53 IHC expression, and the Arg/Arg genotype (p for interaction = 0.09), these findings remain fragile despite reaching statistical significance, warranting careful interpretation. Conclusions: Vitamin D supplementation was associated with more favorable RFS among patients with digestive tract cancer who had both the Arg/Arg genotype and high p53 IHC expression. These exploratory findings warrant further investigation in prospective studies.