Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts
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
Journal of the National Cancer Institute · 217 citations
How it was studied
- Design
- Cohort study (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- World Health Organization
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Cancer Institute
- Government
- NCI NIH HHS
- Government
- NCI
- Government
- NHLBI NIH HHS
- Government
- National Heart, Blood, and Lung Institute
- Government
- National Cancer Institute Intramural Research Program
- Grants
- National Cancer Institute (UM1-CA167462); National Cancer Institute (R03CA183016); National Heart, Lung, and Blood Institute (T32HL125232); National Cancer Institute (U01 CA063673); National Cancer Institute (U01 CA167462); National Cancer Institute (T32CA009001); National Cancer Institute (R03CA212799); National Cancer Institute (P30CA071789); National Cancer Institute (UM1-CA182934); National Cancer Institute (R01CA152071); National Cancer Institute (R25-CA098566)
Based on 8 listed funder(s).
Publication
- Published
- 2018-04-23 · J Natl Cancer Inst · vol. 111 · issue 2 · pp. 158–169
- Publisher
- Oxford University Press
- Cited
- 287 citations · more than 100% of similar papers · 22.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 55 works
- Access
- Open access (repository copy) · PUBLIC-DOMAIN
- Research areas
- Vitamin D Research Studies · Nutritional Studies and Diet · Colorectal Cancer Screening and Detection
- Keywords
- Vitamin D and neurology, Colorectal cancer, Medicine, Epidemiology, Pooling, Internal medicine, Bone health, vitamin D deficiency, Vitamin, Oncology, Cancer, Environmental health, Gastroenterology, Physiology, Osteoporosis, Bone mineral, Computer science
- MeSH
- 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
56 authors
From US, IT, FR, RU, KR, FI, GB, NO
- Marjorie L. McCullough · correspondingAmerican Cancer Society
- Emilie S. ZoltickBoston University; Brigham and Women's Hospital
- Stephanie J. WeinsteinNational Institutes of Health; National Cancer Institute
- Veronika FedirkoEmory University
- Molin WangCancer Research And Biostatistics
- Nancy R. CookBrigham and Women's Hospital; Harvard University
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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