Calcium plus vitamin D supplementation and the risk of colorectal cancer

Jean Wactawski-Wende, Jane Morley Kotchen, Garnet L. Anderson, Annlouise R. Assaf, Robert L. Brunner, Mary Jo O'Sullivan, Karen L. Margolis, Judith K. Ockene, Lawrence Phillips, Linda Pottern, Ross L. Prentice, John Robbins, Thomas E. Rohan, Gloria E. Sarto, Santosh Sharma, Marcia L. Stefanick, Linda Van Horn, Robert B. Wallace, Evelyn Whitlock, Tamsen Bassford & 27 others Shirley A A Beresford, Henry R. Black, Denise E. Bonds, Robert G. Brzyski, Bette Caan, Rowan T. Chlebowski, Barbara Cochrane, Cedric Garland, Margery Gass, Jennifer Hays, Gerardo Heiss, Susan L. Hendrix, Barbara V. Howard, Judith Hsia, F. Allan Hubbell, Rebecca D. Jackson, Karen C. Johnson, Howard Judd, Charles L. Kooperberg, Lewis H. Kuller, Andrea Z. LaCroix, Dorothy S. Lane, Robert D. Langer, Norman L. Lasser, Cora E. Lewis, Marian C. Limacher, JoAnn E. Manson

Research output: Contribution to journalArticle

715 Citations (Scopus)

Abstract

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 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.)

Original languageEnglish (US)
Pages (from-to)684-696
Number of pages13
JournalNew England Journal of Medicine
Volume354
Issue number7
DOIs
StatePublished - Feb 16 2006

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Vitamin D
Colorectal Neoplasms
Calcium
Cholecalciferol
Placebos
Polyps
Incidence
Calcium Carbonate
Women's Health
Primary Prevention
Early Detection of Cancer
Case-Control Studies
Epidemiologic Studies
Confidence Intervals
Recurrence
Serum
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wactawski-Wende, J., Morley Kotchen, J., Anderson, G. L., Assaf, A. R., Brunner, R. L., O'Sullivan, M. J., ... Manson, J. E. (2006). Calcium plus vitamin D supplementation and the risk of colorectal cancer. New England Journal of Medicine, 354(7), 684-696. https://doi.org/10.1056/NEJMoa055222

Calcium plus vitamin D supplementation and the risk of colorectal cancer. / Wactawski-Wende, Jean; Morley Kotchen, Jane; Anderson, Garnet L.; Assaf, Annlouise R.; Brunner, Robert L.; O'Sullivan, Mary Jo; Margolis, Karen L.; Ockene, Judith K.; Phillips, Lawrence; Pottern, Linda; Prentice, Ross L.; Robbins, John; Rohan, Thomas E.; Sarto, Gloria E.; Sharma, Santosh; Stefanick, Marcia L.; Van Horn, Linda; Wallace, Robert B.; Whitlock, Evelyn; Bassford, Tamsen; Beresford, Shirley A A; Black, Henry R.; Bonds, Denise E.; Brzyski, Robert G.; Caan, Bette; Chlebowski, Rowan T.; Cochrane, Barbara; Garland, Cedric; Gass, Margery; Hays, Jennifer; Heiss, Gerardo; Hendrix, Susan L.; Howard, Barbara V.; Hsia, Judith; Hubbell, F. Allan; Jackson, Rebecca D.; Johnson, Karen C.; Judd, Howard; Kooperberg, Charles L.; Kuller, Lewis H.; LaCroix, Andrea Z.; Lane, Dorothy S.; Langer, Robert D.; Lasser, Norman L.; Lewis, Cora E.; Limacher, Marian C.; Manson, JoAnn E.

In: New England Journal of Medicine, Vol. 354, No. 7, 16.02.2006, p. 684-696.

Research output: Contribution to journalArticle

Wactawski-Wende, J, Morley Kotchen, J, Anderson, GL, Assaf, AR, Brunner, RL, O'Sullivan, MJ, Margolis, KL, Ockene, JK, Phillips, L, Pottern, L, Prentice, RL, Robbins, J, Rohan, TE, Sarto, GE, Sharma, S, Stefanick, ML, Van Horn, L, Wallace, RB, Whitlock, E, Bassford, T, Beresford, SAA, Black, HR, Bonds, DE, Brzyski, RG, Caan, B, Chlebowski, RT, Cochrane, B, Garland, C, Gass, M, Hays, J, Heiss, G, Hendrix, SL, Howard, BV, Hsia, J, Hubbell, FA, Jackson, RD, Johnson, KC, Judd, H, Kooperberg, CL, Kuller, LH, LaCroix, AZ, Lane, DS, Langer, RD, Lasser, NL, Lewis, CE, Limacher, MC & Manson, JE 2006, 'Calcium plus vitamin D supplementation and the risk of colorectal cancer', New England Journal of Medicine, vol. 354, no. 7, pp. 684-696. https://doi.org/10.1056/NEJMoa055222
Wactawski-Wende J, Morley Kotchen J, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. New England Journal of Medicine. 2006 Feb 16;354(7):684-696. https://doi.org/10.1056/NEJMoa055222
Wactawski-Wende, Jean ; Morley Kotchen, Jane ; Anderson, Garnet L. ; Assaf, Annlouise R. ; Brunner, Robert L. ; O'Sullivan, Mary Jo ; Margolis, Karen L. ; Ockene, Judith K. ; Phillips, Lawrence ; Pottern, Linda ; Prentice, Ross L. ; Robbins, John ; Rohan, Thomas E. ; Sarto, Gloria E. ; Sharma, Santosh ; Stefanick, Marcia L. ; Van Horn, Linda ; Wallace, Robert B. ; Whitlock, Evelyn ; Bassford, Tamsen ; Beresford, Shirley A A ; Black, Henry R. ; Bonds, Denise E. ; Brzyski, Robert G. ; Caan, Bette ; Chlebowski, Rowan T. ; Cochrane, Barbara ; Garland, Cedric ; Gass, Margery ; Hays, Jennifer ; Heiss, Gerardo ; Hendrix, Susan L. ; Howard, Barbara V. ; Hsia, Judith ; Hubbell, F. Allan ; Jackson, Rebecca D. ; Johnson, Karen C. ; Judd, Howard ; Kooperberg, Charles L. ; Kuller, Lewis H. ; LaCroix, Andrea Z. ; Lane, Dorothy S. ; Langer, Robert D. ; Lasser, Norman L. ; Lewis, Cora E. ; Limacher, Marian C. ; Manson, JoAnn E. / Calcium plus vitamin D supplementation and the risk of colorectal cancer. In: New England Journal of Medicine. 2006 ; Vol. 354, No. 7. pp. 684-696.
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abstract = "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 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.)",
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T1 - Calcium plus vitamin D supplementation and the risk of colorectal cancer

AU - Wactawski-Wende, Jean

AU - Morley Kotchen, Jane

AU - Anderson, Garnet L.

AU - Assaf, Annlouise R.

AU - Brunner, Robert L.

AU - O'Sullivan, Mary Jo

AU - Margolis, Karen L.

AU - Ockene, Judith K.

AU - Phillips, Lawrence

AU - Pottern, Linda

AU - Prentice, Ross L.

AU - Robbins, John

AU - Rohan, Thomas E.

AU - Sarto, Gloria E.

AU - Sharma, Santosh

AU - Stefanick, Marcia L.

AU - Van Horn, Linda

AU - Wallace, Robert B.

AU - Whitlock, Evelyn

AU - Bassford, Tamsen

AU - Beresford, Shirley A A

AU - Black, Henry R.

AU - Bonds, Denise E.

AU - Brzyski, Robert G.

AU - Caan, Bette

AU - Chlebowski, Rowan T.

AU - Cochrane, Barbara

AU - Garland, Cedric

AU - Gass, Margery

AU - Hays, Jennifer

AU - Heiss, Gerardo

AU - Hendrix, Susan L.

AU - Howard, Barbara V.

AU - Hsia, Judith

AU - Hubbell, F. Allan

AU - Jackson, Rebecca D.

AU - Johnson, Karen C.

AU - Judd, Howard

AU - Kooperberg, Charles L.

AU - Kuller, Lewis H.

AU - LaCroix, Andrea Z.

AU - Lane, Dorothy S.

AU - Langer, Robert D.

AU - Lasser, Norman L.

AU - Lewis, Cora E.

AU - Limacher, Marian C.

AU - Manson, JoAnn E.

PY - 2006/2/16

Y1 - 2006/2/16

N2 - 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 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.)

AB - 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 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.)

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DO - 10.1056/NEJMoa055222

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