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Cancer Res. 2019 Jan 1;79(1):274-285. doi: 10.1158/0008-5472.CAN-18-2318. Epub 2018 Nov 13.

A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk.

Author information

1
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
2
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. aurora.perez-cornago@ndph.ox.ac.uk.
3
Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, Maryland.
4
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
5
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota.
6
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan.
7
Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
8
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
9
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, the Netherlands.
10
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.
11
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom.
12
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia.
13
Hellenic Health Foundation, Athens, Greece.
14
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
15
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
16
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
17
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
18
Danish Cancer Society Research Center, Copenhagen, Denmark.
19
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
20
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
21
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
22
Network Aging Research, University of Heidelberg, Heidelberg, Germany.
23
Saarland Cancer Registry, Saarbrücken, Germany.
24
National Institute for Health and Welfare, Helsinki, Finland.
25
The Medical School, University of Western Australia, Perth, Australia.
26
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
27
Western Australian Centre for Health and Ageing, Centre for Medical Research, Harry Perkins Institute of Medical Research, Perth, Australia.
28
Department of Geriatric Medicine, Royal Perth Hospital, Perth, Australia.
29
Department of Psychiatry, Royal Perth Hospital, Perth, Australia.
30
Department of Geriatric Medicine, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia.
31
Departments of Epidemiology and Biostatistics and Urology, University of California, San Francisco, San Francisco, California.
32
Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
33
Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
34
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
35
Department of Community Medicine and Global Health, University of Oslo, Oslo, Norway.
36
Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
37
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
38
Division of Cancer Medicine, Department of Clinical Service, Oslo University Hospital, Oslo, Norway.
39
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
40
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
41
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
42
Queensland Brain Institute, University of Queensland, Queensland, Australia.
43
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
44
Department of Translational Medicine, Clinical Chemistry, Lund University, Skåne University Hospital, Malmö, Sweden.
45
Department of Surgery, Endocrine-Sarcoma Unit, Skåne University Hospital, Lund, Sweden.
46
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
47
Keck School of Medicine, University of Southern California, Los Angeles, California.
48
Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington.
49
SWOG (Formerly the Southwest Oncology Group) Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
50
Department of Biostatistics, University of Washington, Seattle, Washington.
51
Bristol Medical School Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom.
52
Medical Research Council (MRC) University of Bristol Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, United Kingdom.
53
National Institute for Health Research, Bristol Biomedical Research Centre, Bristol, United Kingdom.
54
Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.
55
Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Nutritional Epidemiology Research Team (EREN), Inserm U1153/Inra U1125/Cnam/Paris 13 University, Bobigny, France.
56
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Abstract

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness (P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.

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