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J Natl Cancer Inst. 2019 Feb 1;111(2):158-169. doi: 10.1093/jnci/djy087.

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

Author information

1
Behavioral and Epidemiology Research Program, American Cancer Society, Atlanta, GA.
2
Departments of Epidemiology.
3
Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA.
4
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
5
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
6
Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA.
7
Biostatistics.
8
Channing Division of Network Medicine.
9
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
10
Division of Epidemiology, Department of Population Health and Perlmutter Cancer Center.
11
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
12
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
13
Division of Epidemiology and Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY.
14
Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA.
15
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.
16
Department of Occupational Medicine, Epidemiology and Prevention, Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine, Great Neck, NY.
17
Heartland Assays, LLC, Ames, IA.
18
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
19
Division of Genetics and Epidemiology.
20
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
21
Department of Food and Nutrition, Seoul National University, Seoul, Korea.
22
Department of Health National Institute for Health and Welfare, Helsinki, Finland.
23
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
24
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI.
25
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
26
Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
27
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
28
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
29
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
30
Department of Health Promotion Sciences, University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, AZ.
31
Institute of Basic Medical Sciences, Medical Faculty, University of Oslo, Oslo, Norway.

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.

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