Supplemental calcium in the chemoprevention of colorectal cancer: a systematic review and meta-analysis

Objective: The aim of the review was to assess the evidence for the effectiveness of calcium in reducing the recurrence of adenomas and the occurrence of colorectal cancer among populations at high, intermediate, and low risk of the disease.

Methods: A systematic review of randomized controlled trials (RCTs) was performed to compare calcium alone, and with other agents, versus placebo. Nine databases (Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, Biological Abstracts, the National Research Register, and Current Controlled Trials) were searched for published and unpublished trials. Searches were not restricted by either language or date of publication. All searches were completed in January 2010. Database thesaurus and free text terms for calcium and adenomas or colorectal cancer were used to search for trial reports; additional terms were used to search for other agents of interest, such as NSAIDs and folic acid. Search terms consisted of a combination of terms for colorectal cancer (eg, colon or colorectal and neoplasm or cancer or adenoma) and terms for calcium and RCTs. The initial searches were conducted in June 2008, with update searches in January 2010 to identify more recent studies. The reference lists of relevant studies were also searched for additional papers not identified by the search of electronic databases. Studies had to satisfy the following criteria to be included: RCTs about calcium, with or without other chemopreventive agents, in adults with familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer, or a history of colorectal adenomas, or with no increased baseline risk of colorectal cancer. Meta-analysis was performed. For discrete and numerical outcomes, relative risks (RRs) and risk differences were reported with 95% CIs. The random-effects model was used to account for clinical and methodologic variations between trials.

Results: The original and update searches of electronic databases produced 3835 citations, of which 6 studies (8 papers) met the inclusion criteria. Supplemental calcium had no effect on the number of adenomas in 1 small trial of patients with FAP. Meta-analysis of 3 trials in individuals with a history of adenomas showed a statistically significant reduction in the RR for adenoma recurrence (RR = 0.80 [95% CI, 0.69-0.94], P = 0.006) for those receiving calcium 1200 to 2000 mg/d, but no effect was seen in advanced adenoma (RR = 0.77 [95% CI, 0.501.17], P = NS). Meta-analysis of 2 trials in populations with no increased baseline risk for colorectal cancer suggested that calcium, with or without vitamin D, had no effect on the RR for colorectal cancer (RR = 0.62 [95% CI, 0.11-3.40], P = NS).

Conclusion: Published reports indicated that supplemental calcium was effective for the prevention of adenoma recurrence in populations with a history of adenomas, but no similar effect was apparent in populations at higher or lower risk.