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

Ruth C. Travis (1) , Aurora Perez-Cornago (1) , Paul N. Appleby (1) , Demetrius Albanes (2) , Corinne E. Joshu (3) , Pamela L. Lutsey (4) , Alison M. Mondul (5) , Elizabeth A. Platz (3) , Stephanie J. Weinstein (2) , Tracy M. Layne (2) , Kathy J. Helzlsouer (3) , Kala Visvanathan (3) , Domenico Palli (6) , Petra H. Peeters (7) , Bas Bueno-De-Mesquita (8) , Antonia Trichopoulou (9) , Marc J. Gunter (10) , Konstantinos K. Tsilidis (11) , Maria-Jose Sánchez (12, 13) , Anja Olsen (14) , Hermann Brenner (15) , Ben Schöttker (15) , Laura Perna (15) , Bernd Holleczek (16) , Paul Knekt (17) , Harri Rissanen (17) , Bu B. Yeap (18) , Leon Flicker (18) , Osvaldo P. Almeida (18) , Yuen Yee Elizabeth Wong (18) , June M. Chan (19) , Edward L. Giovannucci (20) , Meir J. Stampfer (20) , Giske Ursin (21) , Randi E. Gislefoss (21) , Tone Bjørge (21) , Haakon E. Meyer (22) , Rune Blomhoff (22) , Shoichiro Tsugane (23) , Norie Sawada (23) , Dallas R. English (24) , Darryl W Eyles (25) , Alicia K. Heath (11) , Elizabeth J. Williamson (26) , Jonas Manjer (27) , Johan Malm (27) , Martin Almquist (27) , Loic Le Marchand (28) , Christopher A. Haiman (29) , Lynne R. Wilkens (28) , Jeannette M. Schenk (30) , Cathy M. Tangen (31) , Amanda Black (2) , Michael B. Cook (2) , Wen-Yi Huang (2) , Regina G. Ziegler (2) , Richard M. Martin (32) , Freddie C. Hamdy (33) , Jenny L. Donovan (32) , David E. Neal (33) , Mathilde Touvier (34) , Serge Hercberg (34) , Pilar Galan (34) , Mélanie Deschasaux (34) , Timothy J. Key (1) , Naomi E. Allen (1)

1 Nuffield Department of Population Health [Oxford]
2 Division of Cancer Epidemiology and Genetics
3 Johns Hopkins Bloomberg School of Public Health [Baltimore]
4 Division of Epidemiology and Community Health
5 University of Michigan [Ann Arbor]
6 ISPRO - Istituto per lo studio, la prevenzione e la rete oncologica = Institute for Cancer Research, Prevention and Clinical Network
7 Julius Center for Health Sciences and Primary Care
8 RIVM - National Institute for Public Health and the Environment [Bilthoven]
9 Hellenic Health Foundation
10 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
11 Imperial College London
12 Granada.ibs - Escuela Andaluza de Salud Publica
13 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
14 Danish Cancer Society Research Center
15 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
16 Saarland Cancer Registry
17 National Institute for Health and Welfare [Helsinki]
18 UWA - The University of Western Australia
19 UC San Francisco - University of California [San Francisco]
20 Harvard T.H. Chan School of Public Health
21 Cancer Registry of Norway, Institute of Population-based Cancer Research
22 UiO - University of Oslo
23 National Cancer Center
24 Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia]
25 Queensland Brain Institute
26 LSHTM - London School of Hygiene and Tropical Medicine
27 Skane University Hospital [Lund]
28 UH - University of Hawai'i [Honolulu]
29 Keck School of Medicine [Los Angeles]
30 Cancer Prevention Program
31 SWOG Southwest Oncology Group
32 University of Bristol [Bristol]
33 Nuffield Department of Surgery
34 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle

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)(2)D 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)(2)D 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.

Mots clés: subsequent development; d metabolites; serum 25-hydroxyvitamin d; polymorphisms; 1,25-dihydroxivatmin-d

Domaines: Santé publique et épidémiologie; Alimentation et Nutrition; Cancer

Ruth C. Travis, Aurora Perez-Cornago, Paul N. Appleby, Demetrius Albanes, Corinne E. Joshu, et al.. A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk. Cancer Research, 2019, 79 (1), pp.274-285. ⟨10.1158/0008-5472.CAN-18-2318⟩. ⟨hal-02438466⟩