title: Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial.
abstract: BACKGROUND
  Calcium and vitamin D both appear to have antineoplastic effects in the large bowel. Although these nutrients are inter-related metabolically in bone and in the normal intestine, their potential interactions in large-bowel carcinogenesis are not well understood.
  
  
  METHODS
  We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center, placebo-controlled randomized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence. Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25-dihydroxy [1,25-(OH)2] vitamin D levels were determined, and the Taq I and Fok I polymorphisms in the vitamin D receptor (VDR) gene were analyzed by polymerase chain reaction. Risk ratios (RRs) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups. Associations of VDR polymorphisms with recurrence risk were also evaluated. All statistical tests were two-sided.
  
  
  RESULTS
  Among subjects with baseline 25-(OH) vitamin D levels at or below the median (29.1 ng/mL), calcium supplementation was not associated with adenoma recurrence, whereas among those with levels above the median, calcium supplementation was associated with a reduced risk (RR = 0.71, 95 % confidence interval [CI] = 0.57 to 0.89, P for interaction =.012). Conversely, serum 25-(OH) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements (RR per 12 ng/mL increase of vitamin D = 0.88, 95% CI = 0.77 to 0.99, P for interaction =.006). VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium.
  
  
  CONCLUSIONS
  Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence. VDR genotype does not appear to be associated with risk.
authors.affiliation: Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA. maria.grau.sepulveda@dartmouth.edu
authors.forename: Maria V
authors.initials: MV
authors.lastname: Grau
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Michael L
authors.initials: ML
authors.lastname: Beach
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Church
authors.forename: David
authors.initials: D
authors.lastname: Heber
mesh_terms: D000236:Adenoma / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D000368:Aged; D016588:Anticarcinogenic Agents / Q000097:blood / Q000627:therapeutic use*; D017610:Calcium Compounds / Q000627:therapeutic use*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D018570:Risk Assessment; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D017610:Calcium Compounds; D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D