Dietary intake of one-carbon nutrients and colorectal cancer risk according to TP53 status

Background Accumulating evidence suggests that one-carbon nutrient intake reduces the risk of colorectal cancer (CRC), although folate fortification has been associated with a temporary increase in CRC incidence. We hypothesized that one-carbon nutrients might harbor preventive and pro-tumor effects on CRC according to tumor conditions and investigated whether the effect of one-carbon nutrients on CRC risk differs by TP53 status. Methods In this prospective study of 21,708 Japanese participants, we applied a multivariable Cox proportional hazards model and examined the associations of dietary intakes of folate, vitamin B6, vitamin B12, and methionine with TP53-overexpressing (N = 192), TP53-non-overexpressing (N = 301), TP53-mutated (N = 180), and TP53 wild-type (N = 134) CRC risk defined by TP53 immunohistochemistry and target sequence. Results Vitamin B12 and methionine intakes were not associated with any CRC subtypes defined by TP53 status. Meanwhile, folate intake was marginally associated with decreased TP53-mutated CRC risk (hazard ratio [HR] with 95% confidence interval [CI] for the highest folate intake quartile compared with the lowest: 0.82 [0.46–1.45]) and increased TP53 wild-type CRC risk (HR: 1.50 [0.78–2.90]). A heterogeneous effect of folate on CRC subtypes was detected (Pheterogeneity= 0.03 between TP53 mutation statuses). In women, the association between vitamin B6 and CRC also differed by TP53 mutation status (Pheterogeneity= 0.007). The HR of vitamin B6 was 0.71 [0.30–1.67] for TP53-mutated CRC and 3.89 [1.79–8.49] for TP53 wild-type CRC. However, no heterogeneous effects were observed between TP53 expression statuses. Conclusion This study supports the hypothesis that the effect of one-carbon nutrient intake on CRC differs according to tumor conditions.