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. HoRonald 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 journalArticlepeer-review

180 Scopus citations


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
Issue number2
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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