# The association between dietary folate intake and risk of colorectal cancer incidence: A systematic review and dose‒response meta-analysis of cohort studies

## TL;DR

This study finds that higher dietary folate intake is linked to a lower risk of colorectal cancer, especially in people with higher BMI, alcohol drinkers, and smokers.

## Contribution

This is the first systematic review and dose-response meta-analysis of cohort studies examining dietary folate intake and colorectal cancer risk.

## Key findings

- Each 100-μg increase in dietary folate intake was associated with a 3% lower risk of colorectal cancer.
- A more protective effect was observed in individuals with higher BMI, alcohol drinkers, and smokers.
- Nonlinear evidence suggests up to 500 μg/day of folate intake is inversely associated with colon cancer.

## Abstract

Dietary components can influence the incidence of colorectal cancer (CRC). Folate is one of the compounds that plays an essential role in the formation of DNA structures, which can lead to or prevent tumorigenesis. The present study is the first systematic review and dose–response meta-analysis of cohort studies evaluating the association between dietary folate intake and the risk of CRC.

The PubMed/Medline, Scopus, and ISI Web of Science databases were systematically searched for cohort studies that assessed the association between folate intake and CRC up to January 2024. Summary relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using a random effects model. Also, linear and nonlinear dose-response analyses were conducted for the dose-response associations between folate intake and risk of CRC.

Eighteen prospective cohort studies with 931,469 participants, 14,860 CRC patients, 3536 colon cancer (CC) patients, and 1075 rectal cancer (RC) patients were included in the analysis. The summary RR of CRC for each 100-μg increase in dietary folate intake was 0.97 (95 % CI: 0.95–0.99, I2: 0.0 %, P-heterogeneity: 0.616), which can be related to BMI (0.97 (95 % CI: 0.95–0.99)); a more protective effect was also observed in subjects who drank alcohol (0.97 (95 % CI: 0.95–0.99)) and those who smoked (0.97 (95 % CI: 0.95–0.99)). Additionally, it was positively related to a 7 % lower risk of CC (0.93 (95 % CI: 0.87–0.99, I2: 33.7 %, P-heterogeneity: 0.159)), and the null relation for RC was 0.98 (95 % CI: 0.90–1.08), I2: 16.6 %, P-heterogeneity: 0.309). There was evidence of nonlinearity in which up to 500 μg/day dietary folate intake was inversely associated with CC (P nonlinearity = 0.04).

The findings showed an inverse association between dietary folate intake and the risk of CRC, especially in high-risk persons, those who have a higher BMI, alcohol drinkers, and smokers.

Image 1

•Folate has a critical role in DNA synthesis.•Folate deficiency in cells leads to DNA structure disturbance and can induce tumorigenesis.•A systematic review and dose response meta-analysis of 18 prospective cohort studies with 931,469 participants.•14,860 colorectal cancer cases, 3536 cases of colon cancer, and 1075 cases of rectal cancer.•Inverse association between each 100-μg increase in dietary folate intake and risk of colorectal and colon cancer.

Folate has a critical role in DNA synthesis.

Folate deficiency in cells leads to DNA structure disturbance and can induce tumorigenesis.

A systematic review and dose response meta-analysis of 18 prospective cohort studies with 931,469 participants.

14,860 colorectal cancer cases, 3536 cases of colon cancer, and 1075 cases of rectal cancer.

Inverse association between each 100-μg increase in dietary folate intake and risk of colorectal and colon cancer.