Calcium intake and colorectal adenoma risk: Dose‐response meta‐analysis of prospective observational studies

Abstract

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 the trials used only a large single dose and were of small sizes, and thus, knowledge of the dose-response relationship and influence on high-risk adenomas is limited. To address these issues, we conducted linear and nonlinear 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 300 mg/day increase was 0.95 (95% CI 5 0.92-0.98; I 2 5 45%; eight studies with 11,005 cases;range of intake 5 333-2,229 mg/day). Evidence of nonlinearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92 (95% CI 5 0.89-0.94) at 1,000 mg/day and 0.87 (95% CI 5 0.84-0.90) at 1,450 mg/day (p nonlinearity < 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 5 0.74-0.81) at 1,000 mg/day and reduced to 0.69 (95% CI 5 0.66-0.73) at 1,450 mg/da (p nonlinearity < 0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300 mg/day increase was 0.96 (95% CI 5 0.93-0.99; I 2 5 0%; three studies with 4,548 cases; range of supplementation 5 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.

Body mass index, calcium supplementation and risk of colorectal adenomas

“…Study treatment ended in December 1996. Baseline serum 25‐hydroxyvitamin D concentrations were measured in 2001 on stored specimens obtained at time of enrollment using a competitive protein binding radioimmunoassay kit from Nichols Institute Diagnostics that used the vitamin D binding protein as the binding agent and H‐labeled 25‐hydroxyvitamin D as the reporter …”

“…Considerable evidence from preclinical and observational studies suggests that calcium supplementation exerts a protective effect against colorectal neoplasia, both colorectal cancer and its main precursor lesion, colorectal adenomas. [1][2][3][4] We conducted two randomized, double-blind, placebo-controlled trials of calcium supplementation (1,200 mg/day elemental calcium as carbonate) for the prevention of new colorectal adenomas in individuals with a recent history of adenomas. These studies were conducted 16 years apart with disparate results.…”

Protective Effect of Dietary Calcium Intake on Esophageal Cancer Risk: A Meta-Analysis of Observational Studies

“…Compared to oral supplements, dietary calcium intake is relatively safe. Thus, many prior meta-analyses have focused on the association between dietary calcium intake and risk of colorectal cancer, breast cancer, and prostate cancer [11,12,13]. However, there is no systemic analysis carried out regarding the relationship between calcium intake and the risk of esophageal cancer.…”

Associations of Calcium and Milk Product Intakes with Incident, Sporadic Colorectal Adenomas

“…Among 16 observational studies (6 prospective cohort and 10 case-control studies), 15 (94%) reported inverse associations, of which 4 were statistically significant. Additionally, in a meta-analysis of 7 prospective studies, a statistically significant 13% lower risk of adenomas was reported among those in the highest relative to the lowest levels of total calcium intake (33). In the same meta-analysis, 8 additional prospective studies were pooled in a dose-response analysis in which a statistically significant 5% lower risk of adenomas per 300 mg/day increase in total calcium intake was reported.…”