Calcium as a chemopreventive agent against colorectal neoplasm: does obesity play a role?

Background: Concerning the chemopreventive potential of calcium against colorectal neoplasms, strong evidence from initial randomized controlled trials (RCTs) of colorectal adenoma has not been confirmed from the most recent large RCT. To explain the conflicting results, a new hypothesis was proposed that the benefit of calcium may be confined to lean individuals. Methods: To test this hypothesis, we examined heterogeneity of the associations of calcium intake with adenoma and CRC, using data from the most recent meta-analyses of observational studies and conducting subgroup analysis by average body mass index (BMI) of study population. Results: An inverse association of calcium intake with adenoma and CRC did not vary by population average BMI. By anatomical subsites of CRC, while there was no significant evidence of heterogeneity by population average BMI (P_{heterogeneity} > 0.05), the benefit of calcium was confined to studies with population average BMI of ≥25 kg/m² for both colon cancer and rectal cancer, contradicting the hypothesis. Conclusions: In our study-level meta-analysis, we found no evidence to support that the chemopreventive potential of calcium, if real, may be stronger in leaner individuals.