Evidence from randomized controlled trials suggests that calcium may protect against recurrence of colorectal adenomas, which could lead to the subsequent prevention of cancer. Yet, because the trials used only a large single dose and were of small sizes, knowledge of the dose-response relationship and influence on high-risk adenomas is limited. To address these issues, we conducted linear and non-linear dose-response meta-analyses primarily based on prospective observational studies published up to July 2014 identified from PubMed and Embase. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated for total and supplemental calcium intake, respectively, using a random-effects model. For total calcium intake, summary RR for each 300mg/day increase was 0.95(95% CI=0.92-0.98; I(2) =45%; 8 studies with 11,005 cases; range of intake=333-2,229 mg/day). Evidence of non-linearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92(95% CI=0.89-0.94) at 1000 mg/day and 0.87(95% CI=0.84-0.90) at 1450 mg/day (Pnon -linearity <0.01). Associations were stronger for high-risk adenomas (≥1 cm in diameter, (tubulo)villous histology, dysplasia, or multiplicity): approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.77(95% CI=0.74-0.81) at 1000 mg/day and reduced to 0.69(95% CI=0.66-0.73) at 1450 mg/da (Pnon -linearity <0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300mg/day increase was 0.96(95% CI=0.93-0.99; I(2) =0%; 3 studies with 4,548 cases; range of supplementation=0-1,366 mg/day). In conclusion, calcium intake may continue to decrease the risk of adenomas, particularly high-risk adenomas, over a wide range of calcium intake.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)