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.).
Wactawski-Wende
Jean
J
Department of Social and Preventive Medicine, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, USA. jww@buffalo.edu
Kotchen
Jane Morley
JM
Anderson
Garnet L
GL
Assaf
Annlouise R
AR
Brunner
Robert L
RL
O'Sullivan
Mary Jo
MJ
Margolis
Karen L
KL
Ockene
Judith K
JK
Phillips
Lawrence
L
Pottern
Linda
L
Prentice
Ross L
RL
Robbins
John
J
Rohan
Thomas E
TE
Sarto
Gloria E
GE
Sharma
Santosh
S
Stefanick
Marcia L
ML
Van Horn
Linda
L
Wallace
Robert B
RB
Whitlock
Evelyn
E
Bassford
Tamsen
T
Beresford
Shirley A A
SA
Black
Henry R
HR
Bonds
Denise E
DE
Brzyski
Robert G
RG
Caan
Bette
B
Chlebowski
Rowan T
RT
Cochrane
Barbara
B
Garland
Cedric
C
Gass
Margery
M
Hays
Jennifer
J
Heiss
Gerardo
G
Hendrix
Susan L
SL
Howard
Barbara V
BV
Hsia
Judith
J
Hubbell
F Allan
FA
Jackson
Rebecca D
RD
Johnson
Karen C
KC
Judd
Howard
H
Kooperberg
Charles L
CL
Kuller
Lewis H
LH
LaCroix
Andrea Z
AZ
Lane
Dorothy S
DS
Langer
Robert D
RD
Lasser
Norman L
NL
Lewis
Cora E
CE
Limacher
Marian C
MC
Manson
JoAnn E
JE
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