title: 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 = 0.92-0.98; I(2)  = 45%; eight studies with 11,005 cases; range of intake = 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 = 0.89-0.94) at 1,000 mg/day and 0.87 (95% CI = 0.84-0.90) at 1,450 mg/day (pnonlinearity  < 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 1,000 mg/day and reduced to 0.69 (95% CI = 0.66-0.73) at 1,450 mg/da (pnonlinearity  < 0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300 mg/day increase was 0.96 (95% CI = 0.93-0.99; I(2)  = 0%; three 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.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA; Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors.forename: NaNa
authors.initials: N
authors.lastname: Keum
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Darren C
authors.initials: DC
authors.lastname: Greenwood
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
mesh_terms: D000236:Adenoma / Q000453:epidemiology* / Q000209:etiology*; D002118:Calcium / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D019587:Dietary Supplements; D006801:Humans; D011446:Prospective Studies; D012306:Risk
chemical_list: D002118:Calcium
keywords: calcium intake; colorectal adenomas; dose-response meta-analysis; prospective observational studies