Calcium plus vitamin D supplementation and the risk of colorectal cancer.
BACKGROUND
Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.


METHODS
We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.


RESULTS
The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.


CONCLUSIONS
Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).
Department of Social and Preventive Medicine, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, USA. jww@buffalo.edu
Jean
J
Wactawski-Wende
Jane Morley
JM
Kotchen
Garnet L
GL
Anderson
Annlouise R
AR
Assaf
Robert L
RL
Brunner
Mary Jo
MJ
O'Sullivan
Karen L
KL
Margolis
Judith K
JK
Ockene
Lawrence
L
Phillips
Linda
L
Pottern
Ross L
RL
Prentice
John
J
Robbins
Thomas E
TE
Rohan
Gloria E
GE
Sarto
Santosh
S
Sharma
Marcia L
ML
Stefanick
Linda
L
Van Horn
Robert B
RB
Wallace
Evelyn
E
Whitlock
Tamsen
T
Bassford
Shirley A A
SA
Beresford
Henry R
HR
Black
Denise E
DE
Bonds
Robert G
RG
Brzyski
Bette
B
Caan
Rowan T
RT
Chlebowski
Barbara
B
Cochrane
Cedric
C
Garland
Margery
M
Gass
Jennifer
J
Hays
Gerardo
G
Heiss
Susan L
SL
Hendrix
Barbara V
BV
Howard
Judith
J
Hsia
F Allan
FA
Hubbell
Rebecca D
RD
Jackson
Karen C
KC
Johnson
Howard
H
Judd
Charles L
CL
Kooperberg
Lewis H
LH
Kuller
Andrea Z
AZ
LaCroix
Dorothy S
DS
Lane
Robert D
RD
Langer
Norman L
NL
Lasser
Cora E
CE
Lewis
Marian C
MC
Limacher
JoAnn E
JE
Manson
D000230:Adenocarcinoma / Q000453:epidemiology / Q000517:prevention & control*; D000368:Aged; D002118:Calcium / Q000627:therapeutic use; D002119:Calcium Carbonate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003111:Colonic Polyps / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D014807:Vitamin D / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D004338:Drug Combinations; D014807:Vitamin D; D002119:Calcium Carbonate; D002118:Calcium