Circulating Vitamin D and colorectal cancer risk

An international pooling project of 17 cohorts

Marjorie L. McCullough, Emilie S. Zoltick, Stephanie J. Weinstein, Veronika Fedirko, Molin Wang, Nancy R. Cook, A. Heather Eliassen, Anne Zeleniuch-Jacquotte, Claudia Agnoli, Demetrius Albanes, Matthew J. Barnett, Julie E. Buring, Peter T. Campbell, Tess V. Clendenen, Neal D. Freedman, Susan M. Gapstur, Edward L. Giovannucci, Gary G. Goodman, Christopher A. Haiman, Gloria Y.F. Ho & 36 others Ronald L. Horst, Tao Hou, Wen Yi Huang, Mazda Jenab, Michael E. Jones, Corinne E. Joshu, Vittorio Krogh, I. Min Lee, Jung Eun Lee, Satu Männistö, Loic Le Marchand, Alison M. Mondul, Marian L. Neuhouser, Elizabeth A Platz, Mark P. Purdue, Elio Riboli, Trude Eid Robsahm, Thomas E. Rohan, Shizuka Sasazuki, Minouk J. Schoemaker, Sabina Sieri, Meir J. Stampfer, Anthony J. Swerdlow, Cynthia A. Thomson, Steinar Tretli, Schoichiro Tsugane, Giske Ursin, Kala Visvanathan, Kami K. White, Kana Wu, Shiaw Shyuan Yaun, Xuehong Zhang, Walter C. Willett, Mitchel H. Gail, Regina G. Ziegler, Stephanie A. Smith-Warner

Research output: Contribution to journalArticle

Abstract

Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneitybysex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. Conclusions: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

Original languageEnglish (US)
Pages (from-to)158-169
Number of pages12
JournalJournal of the National Cancer Institute
Volume111
Issue number2
DOIs
StatePublished - Jan 1 2019

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Vitamin D
Colorectal Neoplasms
Confidence Intervals
National Academies of Science, Engineering, and Medicine (U.S.) Health and Medicine Division
Bone and Bones
Health
Risk Reduction Behavior
Epidemiologic Studies
Carcinogenesis
Body Mass Index
Logistic Models

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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McCullough, M. L., Zoltick, E. S., Weinstein, S. J., Fedirko, V., Wang, M., Cook, N. R., ... Smith-Warner, S. A. (2019). Circulating Vitamin D and colorectal cancer risk: An international pooling project of 17 cohorts. Journal of the National Cancer Institute, 111(2), 158-169. https://doi.org/10.1093/jnci/djy087

Circulating Vitamin D and colorectal cancer risk : An international pooling project of 17 cohorts. / McCullough, Marjorie L.; Zoltick, Emilie S.; Weinstein, Stephanie J.; Fedirko, Veronika; Wang, Molin; Cook, Nancy R.; Eliassen, A. Heather; Zeleniuch-Jacquotte, Anne; Agnoli, Claudia; Albanes, Demetrius; Barnett, Matthew J.; Buring, Julie E.; Campbell, Peter T.; Clendenen, Tess V.; Freedman, Neal D.; Gapstur, Susan M.; Giovannucci, Edward L.; Goodman, Gary G.; Haiman, Christopher A.; Ho, Gloria Y.F.; Horst, Ronald L.; Hou, Tao; Huang, Wen Yi; Jenab, Mazda; Jones, Michael E.; Joshu, Corinne E.; Krogh, Vittorio; Lee, I. Min; Lee, Jung Eun; Männistö, Satu; Le Marchand, Loic; Mondul, Alison M.; Neuhouser, Marian L.; Platz, Elizabeth A; Purdue, Mark P.; Riboli, Elio; Robsahm, Trude Eid; Rohan, Thomas E.; Sasazuki, Shizuka; Schoemaker, Minouk J.; Sieri, Sabina; Stampfer, Meir J.; Swerdlow, Anthony J.; Thomson, Cynthia A.; Tretli, Steinar; Tsugane, Schoichiro; Ursin, Giske; Visvanathan, Kala; White, Kami K.; Wu, Kana; Yaun, Shiaw Shyuan; Zhang, Xuehong; Willett, Walter C.; Gail, Mitchel H.; Ziegler, Regina G.; Smith-Warner, Stephanie A.

In: Journal of the National Cancer Institute, Vol. 111, No. 2, 01.01.2019, p. 158-169.

Research output: Contribution to journalArticle

McCullough, ML, Zoltick, ES, Weinstein, SJ, Fedirko, V, Wang, M, Cook, NR, Eliassen, AH, Zeleniuch-Jacquotte, A, Agnoli, C, Albanes, D, Barnett, MJ, Buring, JE, Campbell, PT, Clendenen, TV, Freedman, ND, Gapstur, SM, Giovannucci, EL, Goodman, GG, Haiman, CA, Ho, GYF, Horst, RL, Hou, T, Huang, WY, Jenab, M, Jones, ME, Joshu, CE, Krogh, V, Lee, IM, Lee, JE, Männistö, S, Le Marchand, L, Mondul, AM, Neuhouser, ML, Platz, EA, Purdue, MP, Riboli, E, Robsahm, TE, Rohan, TE, Sasazuki, S, Schoemaker, MJ, Sieri, S, Stampfer, MJ, Swerdlow, AJ, Thomson, CA, Tretli, S, Tsugane, S, Ursin, G, Visvanathan, K, White, KK, Wu, K, Yaun, SS, Zhang, X, Willett, WC, Gail, MH, Ziegler, RG & Smith-Warner, SA 2019, 'Circulating Vitamin D and colorectal cancer risk: An international pooling project of 17 cohorts', Journal of the National Cancer Institute, vol. 111, no. 2, pp. 158-169. https://doi.org/10.1093/jnci/djy087
McCullough, Marjorie L. ; Zoltick, Emilie S. ; Weinstein, Stephanie J. ; Fedirko, Veronika ; Wang, Molin ; Cook, Nancy R. ; Eliassen, A. Heather ; Zeleniuch-Jacquotte, Anne ; Agnoli, Claudia ; Albanes, Demetrius ; Barnett, Matthew J. ; Buring, Julie E. ; Campbell, Peter T. ; Clendenen, Tess V. ; Freedman, Neal D. ; Gapstur, Susan M. ; Giovannucci, Edward L. ; Goodman, Gary G. ; Haiman, Christopher A. ; Ho, Gloria Y.F. ; Horst, Ronald L. ; Hou, Tao ; Huang, Wen Yi ; Jenab, Mazda ; Jones, Michael E. ; Joshu, Corinne E. ; Krogh, Vittorio ; Lee, I. Min ; Lee, Jung Eun ; Männistö, Satu ; Le Marchand, Loic ; Mondul, Alison M. ; Neuhouser, Marian L. ; Platz, Elizabeth A ; Purdue, Mark P. ; Riboli, Elio ; Robsahm, Trude Eid ; Rohan, Thomas E. ; Sasazuki, Shizuka ; Schoemaker, Minouk J. ; Sieri, Sabina ; Stampfer, Meir J. ; Swerdlow, Anthony J. ; Thomson, Cynthia A. ; Tretli, Steinar ; Tsugane, Schoichiro ; Ursin, Giske ; Visvanathan, Kala ; White, Kami K. ; Wu, Kana ; Yaun, Shiaw Shyuan ; Zhang, Xuehong ; Willett, Walter C. ; Gail, Mitchel H. ; Ziegler, Regina G. ; Smith-Warner, Stephanie A. / Circulating Vitamin D and colorectal cancer risk : An international pooling project of 17 cohorts. In: Journal of the National Cancer Institute. 2019 ; Vol. 111, No. 2. pp. 158-169.
@article{17975935edfc447d8f7b242835266376,
title = "Circulating Vitamin D and colorectal cancer risk: An international pooling project of 17 cohorts",
abstract = "Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1{\%} of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31{\%} higher colorectal cancer risk (RR = 1.31, 95{\%} confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19{\%} (RR = 0.81, 95{\%} CI = 0.67 to 0.99) and 27{\%} (RR = 0.73, 95{\%} CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95{\%} CI = 0.67 to 1.24, 3.5{\%} of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19{\%} lower in women (RR = 0.81, 95{\%} CI = 0.75 to 0.87) and 7{\%} lower in men (RR = 0.93, 95{\%} CI = 0.86 to 1.00) (two-sided Pheterogeneitybysex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. Conclusions: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.",
author = "McCullough, {Marjorie L.} and Zoltick, {Emilie S.} and Weinstein, {Stephanie J.} and Veronika Fedirko and Molin Wang and Cook, {Nancy R.} and Eliassen, {A. Heather} and Anne Zeleniuch-Jacquotte and Claudia Agnoli and Demetrius Albanes and Barnett, {Matthew J.} and Buring, {Julie E.} and Campbell, {Peter T.} and Clendenen, {Tess V.} and Freedman, {Neal D.} and Gapstur, {Susan M.} and Giovannucci, {Edward L.} and Goodman, {Gary G.} and Haiman, {Christopher A.} and Ho, {Gloria Y.F.} and Horst, {Ronald L.} and Tao Hou and Huang, {Wen Yi} and Mazda Jenab and Jones, {Michael E.} and Joshu, {Corinne E.} and Vittorio Krogh and Lee, {I. Min} and Lee, {Jung Eun} and Satu M{\"a}nnist{\"o} and {Le Marchand}, Loic and Mondul, {Alison M.} and Neuhouser, {Marian L.} and Platz, {Elizabeth A} and Purdue, {Mark P.} and Elio Riboli and Robsahm, {Trude Eid} and Rohan, {Thomas E.} and Shizuka Sasazuki and Schoemaker, {Minouk J.} and Sabina Sieri and Stampfer, {Meir J.} and Swerdlow, {Anthony J.} and Thomson, {Cynthia A.} and Steinar Tretli and Schoichiro Tsugane and Giske Ursin and Kala Visvanathan and White, {Kami K.} and Kana Wu and Yaun, {Shiaw Shyuan} and Xuehong Zhang and Willett, {Walter C.} and Gail, {Mitchel H.} and Ziegler, {Regina G.} and Smith-Warner, {Stephanie A.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/jnci/djy087",
language = "English (US)",
volume = "111",
pages = "158--169",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Circulating Vitamin D and colorectal cancer risk

T2 - An international pooling project of 17 cohorts

AU - McCullough, Marjorie L.

AU - Zoltick, Emilie S.

AU - Weinstein, Stephanie J.

AU - Fedirko, Veronika

AU - Wang, Molin

AU - Cook, Nancy R.

AU - Eliassen, A. Heather

AU - Zeleniuch-Jacquotte, Anne

AU - Agnoli, Claudia

AU - Albanes, Demetrius

AU - Barnett, Matthew J.

AU - Buring, Julie E.

AU - Campbell, Peter T.

AU - Clendenen, Tess V.

AU - Freedman, Neal D.

AU - Gapstur, Susan M.

AU - Giovannucci, Edward L.

AU - Goodman, Gary G.

AU - Haiman, Christopher A.

AU - Ho, Gloria Y.F.

AU - Horst, Ronald L.

AU - Hou, Tao

AU - Huang, Wen Yi

AU - Jenab, Mazda

AU - Jones, Michael E.

AU - Joshu, Corinne E.

AU - Krogh, Vittorio

AU - Lee, I. Min

AU - Lee, Jung Eun

AU - Männistö, Satu

AU - Le Marchand, Loic

AU - Mondul, Alison M.

AU - Neuhouser, Marian L.

AU - Platz, Elizabeth A

AU - Purdue, Mark P.

AU - Riboli, Elio

AU - Robsahm, Trude Eid

AU - Rohan, Thomas E.

AU - Sasazuki, Shizuka

AU - Schoemaker, Minouk J.

AU - Sieri, Sabina

AU - Stampfer, Meir J.

AU - Swerdlow, Anthony J.

AU - Thomson, Cynthia A.

AU - Tretli, Steinar

AU - Tsugane, Schoichiro

AU - Ursin, Giske

AU - Visvanathan, Kala

AU - White, Kami K.

AU - Wu, Kana

AU - Yaun, Shiaw Shyuan

AU - Zhang, Xuehong

AU - Willett, Walter C.

AU - Gail, Mitchel H.

AU - Ziegler, Regina G.

AU - Smith-Warner, Stephanie A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneitybysex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. Conclusions: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

AB - Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneitybysex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. Conclusions: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

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U2 - 10.1093/jnci/djy087

DO - 10.1093/jnci/djy087

M3 - Article

VL - 111

SP - 158

EP - 169

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 2

ER -