title: Risk of prostate cancer in a randomized clinical trial of calcium supplementation.
abstract: BACKGROUND
  In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue.
  
  
  METHODS
  We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels.
  
  
  RESULTS
  After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk.
  
  
  CONCLUSIONS
  In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.
authors.affiliation: Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Michael
authors.initials: M
authors.lastname: Beach
authors.forename: Kristin
authors.initials: K
authors.lastname: Wallace
authors.forename: Maria V
authors.initials: MV
authors.lastname: Grau
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Jack S
authors.initials: JS
authors.lastname: Mandel
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: E Robert
authors.initials: ER
authors.lastname: Greenberg
mesh_terms: D000236:Adenoma / Q000517:prevention & control*; D000368:Aged; D000863:Antacids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002119:Calcium Carbonate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D019587:Dietary Supplements; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010919:Placebos; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000209:etiology*; D012307:Risk Factors; D014807:Vitamin D / Q000008:administration & dosage
chemical_list: D000863:Antacids; D010919:Placebos; D014807:Vitamin D; D002119:Calcium Carbonate