Vitamin D Intake and the Risk of Colorectal Cancer: An Updated Meta-Analysis and Systematic Review of Case-Control and Prospective Cohort Studies

Cancers

Jun 2021

DOI: 10.3390/cancers13112814

Citations:44

Influential Citations:1

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Observational meta-analysis of case-control and prospective cohort studies in adults from multiple countries; 31 case-control studies (47,540 cases; 70,567 controls) and prospective cohorts with 14,676 CRC-incident cases among 808,130 participants; follow-up ranged from 5 to 16 years.

Results

Dietary vitamin D intake is associated with reduced CRC risk in case-control studies (OR 0.75; 95% CI 0.67-0.85). In prospective cohorts, dietary vitamin D shows no significant association with CRC incidence (HR 0.94; 95% CI 0.79-1.11). For colorectal cancer subsites, dietary vitamin D reduces colon cancer risk (OR 0.82; 0.67-0.98) and rectal cancer risk (OR 0.67; 0.51-0.87), with stronger effect in women for rectal cancer (0.57; 0.39-0.82). Supplemental vitamin D shows inverse associations in case-control data for colon cancer (0.57; 0.37-0.88) but not rectal cancer; total vitamin D shows inverse association with CRC in case-control (0.77; 0.66-0.90). In prospective cohorts, supplemental vitamin D is associated with lower CRC risk (0.80; 0.66-0.96) and total vitamin D with lower CRC risk (0.80; 0.67-0.95) in all subjects, with stronger effects in men (supplemental 0.65; 0.50-0.85; total 0.71; 0.57-0.90) and non-significant in women (0.96; 0.81-1.15). Overall, higher vitamin D intake (dietary and supplements) may reduce CRC risk; the signal is clearer for dietary vitamin D in case-control data; prospective evidence is less consistent. More long-term, high-quality studies and randomized trials are needed to confirm.

Limitations

Heterogeneity across study designs and populations; residual confounding and measurement errors in vitamin D intake assessment; limited publication bias assessment due to small numbers of studies; outliers influencing results in some analyses; inability to determine optimal dose or exposure duration; sun exposure and other confounders not uniformly controlled.

Abstract

Simple Summary Colorectal cancer (CRC) is the third most diagnosed cancer in men and the second in women worldwide, being the second most deadly cancer worldwide. The evidence coming from experimental studies suggest a protective effect of vitamin D intake on the risk of CRC. Different studies have shown that vitamin D may play a chemopreventive role in colorectal adenoma incidence, malignant transformation and progression. Our objective was to conduct an updated systematic review and meta-analysis of both case-control and prospective cohort studies on vitamin D intake and CRC. This manuscript provides a complete and updated state-of-the-art about vitamin D intake and CRC risk. Abstract Obesity, a sedentary lifestyle, high red meat consumption and alcohol, and tobacco are considered the driving factors behind colorectal cancer (CRC) worldwide. Both diet and lifestyle are recognized to play an important role in the prevention of CRC. Forty years later, the vitamin D–cancer hypothesis is considered consistent. However, the relationship between low vitamin D intake and CRC is still controversial. The aim of this meta-analysis is to determine the associations between Vitamin D intake and CRC. MEDLINE-PubMed and Cochrane databases were searched up to May 2020 for studies evaluating the association between vitamin D intake (from foods and supplements) and CRC. Two reviewers, working independently, screened all titles and abstracts to identify the studies that met the inclusion criteria (case-control or prospective cohort (PC) studies published in English). Data were pooled by the generic inverse variance method using a random or fixed effect model. Heterogeneity was identified using the Cochran Q-test and quantified by the I2 statistic. A total of 31 original studies were included for the quantitative meta-analysis, comprising a total 47.540 cases and 70.567 controls in case-control studies, and a total of 14.676 CRC-incident cases (out of 808.130 subjects in PC studies) from 17 countries. A significant 25% lower risk was reported comparing the highest vs. the lowest dietary vitamin D consumption and CRC risk (odds ratio (95% confidence interval): 0.75 (0.67; 0.85)) in case-control studies, whereas a non-significant association was reported in case of prospective studies (hazard ratio (95% confidence interval): 0.94 (0.79; 1.11). The present meta-analysis demonstrates that high dietary vitamin D is associated to CRC prevention. However, larger and high-quality prospective studies and clinical trials are warranted to confirm this association. show less