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

## TL;DR

This study found that the effect of one-carbon nutrients like folate on colorectal cancer risk depends on the TP53 status of the tumor.

## Contribution

The study reveals that one-carbon nutrients may have both preventive and protumor effects depending on TP53 mutation status.

## Key findings

- Folate intake was linked to reduced risk of TP53-mutated CRC but increased risk of TP53 wild-type CRC.
- Vitamin B6 showed a strong protective effect for TP53-mutated CRC but a harmful effect for TP53 wild-type CRC in women.
- No significant associations were found for vitamin B12 and methionine with CRC subtypes.

## Abstract

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 protumor 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-nonoverexpressing (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 (HR = 0.82, 95% CI = 0.46 to 1.45) and increased TP53 wild-type CRC risk (HR = 1.50, 95% CI = 0.78 to 2.90). A heterogeneous effect of folate on CRC subtypes was detected (P = .03 for heterogeneity between TP53 mutation statuses). In women, the association between vitamin B6 and CRC also differed by TP53 mutation status (P = .007 for heterogeneity). The hazard ratio of vitamin B6 was 0.71 (95% CI = 0.30 to 1.67) for TP53-mutated CRC and 3.89 (95% CI = 1.79 to 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.