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 Pheterogeneity by sex = .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.

• Authors: 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, 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
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 111 Issue 2 Pg. 158-169 (02 01 2019) ISSN: 1460-2105 [Electronic] United States
• PMID: 29912394 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: Published by Oxford University Press 2018.

Chemical References

• Vitamins
• Vitamin D

Topics

• Aged
• Case-Control Studies
• Colorectal Neoplasms (blood, etiology, pathology)
• Female
• Follow-Up Studies
• Humans
• International Agencies
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Risk Factors
• Vitamin D (blood)
• Vitamin D Deficiency (blood, complications)
• Vitamins (blood)