Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: A systematic review and meta-analysis

Colorectal cancer (CRC) exhibits a linear progression from normal colonic epithelium, adenoma initiation, carcinoma transformation and even to metastasis. Diet changes might influence carcinogenesis and prognosis. We aimed to determine the effects of vitamin D and calcium on colorectal adenoma incidence, malignancy development and prognosis.Systematic literature searches (PubMed, Embase, and Cochrane Library databases) and hand searches were performed by September 30, 2019. A random-effects model was adopted to pool relative ratios (RRs) for colorectal tumour incidence or hazard ratios (HRs) for CRC mortality. Stratified analyses were performed by gender, tumour location, calcium intake level and ethnic group.Total 854,195 cases from 166 studies were included. The colorectal adenoma incidence was inversely correlated with the circulating 25-hydroxyvitamin D [25(OH)D] level (RR: 0.80, 95% CI: 0.71-0.89), vitamin D intake (RR: 0.87, 95% CI: 0.82-0.92) and calcium intake (RR: 0.86, 95% CI: 0.81-0.91). The CRC incidence was decreased by circulating 25(OH)D (RR: 0.67, 95% CI: 0.59-0.77), vitamin D intake (RR: 0.85, 95% CI: 0.78-0.93) and calcium intake (RR: 0.75, 95% CI: 0.70-0.79). High-level circulating 25(OH)D triggered better overall survival (HR: 0.67, 95% CI: 0.57-0.79) and CRC-specific survival (HR: 0.63, 95% CI: 0.53-0.74). Stratified analyses showed that vitamin D and calcium significantly suppressed colorectal tumour incidence among women. Left-sided CRC risk was reversely related to circulating 25(OH)D (RR: 0.60, 95% CI: 0.41-0.88) and vitamin D intake (RR: 0.73, 95% CI: 0.57-0.93). Circulating 25(OH)D decreased colorectal adenoma (RR: 0.63, 95% CI: 0.48-0.82) and CRC (RR: 0.69, 95% CI: 0.56-0.86) risk in populations with higher calcium intake. European and American populations benefited more from vitamin D intake against colorectal tumour. A significant dose-response relationship was observed between intake of vitamin D or calcium and colorectal tumour incidence.Vitamin D and calcium play additively chemopreventive roles in colorectal adenoma incidence, malignant transformation and progression, especially for women and left-sided CRC patients.