Additively Protective Effects of Vitamin D and Calcium Against Colorectal Adenoma Incidence, Malignant Transformation and Progression: A Systematic Review and Dose-Response Meta-Analysis

Abstract

Background: Colorectal cancer (CRC) exhibits a classical linear progression from normal colonic epithelium, adenoma initiation, malignant transformation to carcinoma and even to metastasis. Diet and lifestyle changes might have significant effects on carcinogenesis, recurrence and metastasis. We sought to determine the effects of vitamin D and calcium on colorectal adenoma incidence, malignancy development and prognosis. Methods: We searched and extracted data in the PubMed, Embase, and Cochrane Library databases by Dec 31, 2018 and pooled the relative ratio (RRs) for colorectal tumour incidence or the hazard ratio (HRs) for CRC overall mortality using random-effects model. Then dose-response meta-analysis and stratified analysis by gender, tumour location, calcium intake level and ethnic group were performed. Findings: Total 488722 cases from 146 studies were incorporated into this study. Both colorectal adenoma and cancer incidence were negatively correlated with circulating 25(OH)D, vitamin D intake and calcium intake. However, high-level circulating 25(OH)D was associated with better overall survival and CRC-specific survival. The stratified analysis showed that vitamin D and calcium played significant suppressor roles only in female colorectal adenoma and CRC incidence. Interestingly, there is a inverse relationship between left-sided CRC and circulating 25(OH)D and vitamin D intake. Moreover, populations with higher levels of circulating 25(OH)D showed a lower risk of colorectal adenoma and CRC in higher calcium intake groups. Additionally, European and American populations benefited more from the protective effect of vitamin D intake against colorectal adenoma and CRC. Moreover, a significant dose-response relationship was observed between vitamin D or calcium intake and incidence of colorectal adenoma and CRC. Interpretation: Vitamin D and calcium play additively chemopreventive roles in colorectal adenoma incidence, malignant transformation and progression, especially among females and left-sided CRC patients. Funding: The National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities and the 111 Project. Declaration of Interest: The authors declare no potential conflicts of interest.