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

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 I(2) 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.