Meta-Analyses of Vitamin D Intake, 25-Hydroxyvitamin D Status, Vitamin D Receptor Polymorphisms, and Colorectal Cancer Risk

Background: Our objective was to conduct a systematic review and meta-analysis of prospective studies on colorectal cancer (CRC) and vitamin D intake and 25-hydroxyvitamin D status, as part of the World Cancer Research Fund Continuous Update Project. We also aimed at conducting meta-analysis of all studies on CRC and vitamin D receptor (VDR) single-nucleotide polymorphisms. Methods: Relevant studies were identified in PubMed (up to June 2010). Inclusion criteria were original and peer-reviewed publications with a prospective design (for studies on vitamin D intake or status). Random effects of dose-response meta-analyses were performed on cancer incidence. Results: We observed inverse associations of CRC risk with dietary vitamin D [summary relative risk (RR) per 100 IU/day = 0.95, 95% CI: 0.93-0.98; 10 studies; range of intake (midpoints) = 39-719 IU/day] and serum/plasma 25-hydroxyvitamin D (RR per 100 IU/L = 0.96, 0.94-0.97; 6 studies; range = 200-1,800 IU/L), but not with total vitamin D (5 studies). Supplemental (2 studies; range = 0-600 IU/day) and total (4 studies; range = 79-732 IU/day) vitamin D intake and 25-hydroxyvitamin D status (6 studies; range = 200-1,800 IU/L) were inversely associated with colon cancer risk. We did not observe statistically significant associations between FokI, PolyA, TaqI, Cdx2, and ApaI VDR polymorphisms and CRC risk. The BsmI polymorphism was associated with a lower CRC risk (RR = 0.57, 0.36-0.89 for BB versus bb, 8 studies). Conclusions: These meta-analyses support the evidence of an inverse association between vitamin D intake, 25-hydroxyvitamin D status, and the BsmI VDR polymorphism and CRC risk. Impact: Improving vitamin D status could be potentially beneficial against CRC incidence. Cancer Epidemiol Biomarkers Prev; 20(5); 1003-16. (C) 2011 AACR.