Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.
Date
2019-02-01Author
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, W-Y
Jenab, M
Jones, ME
Joshu, CE
Krogh, V
Lee, I-M
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, S-S
Zhang, X
Willett, WC
Gail, MH
Ziegler, RG
Smith-Warner, SA
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Colorectal Neoplasms
Vitamin D Deficiency
Vitamins
Vitamin D
Prognosis
Risk Factors
Case-Control Studies
Follow-Up Studies
Prospective Studies
Aged
Middle Aged
International Agencies
Female
Male
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2018-04-16
License start date
2019-02
Citation
Journal of the National Cancer Institute, 2019, 111 (2), pp. 158 - 169
Publisher
OXFORD UNIV PRESS INC