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Article

Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts

by Marjare 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 Gapstur; Edward L. Giovannucci; Gary G. Goodman; Christopher A. Haiman; Gloria Y. F. Ho; 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 Mannisto; 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

2019

Subjects
  • Health Sciences, Oncology
  • Health Sciences, Nutrition
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Abstract:Close

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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