A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk
Authors: Travis Ruth C. , Perez-Cornago Aurora , Appleby Paul N. , Albanes Demetrius , Joshu Corinne E. , Lutsey Pamela L. , Mondul Alison M. , Platz Elizabeth A. , Weinstein Stephanie J. , Layne Tracy M. , Helzlsouer Kathy J. , Visvanathan Kala , Palli Domenico , Peeters Petra H. , Bueno-de-Mesquita Bas , Trichopoulou Antonia , Gunter Marc J. , Tsilidis Konstantinos K. , Sánchez Maria-Jose , Olsen Anja , Brenner Hermann , Schöttker Ben , Perna Laura , Holleczek Bernd , Knekt Paul , Rissanen Harri , Yeap Bu B. , Flicker Leon , Almeida Osvaldo P. , Wong Yuen Yee Elizabeth , Chan June M. , Giovannucci Edward L. , Stampfer Meir J. , Ursin Giske , Gislefoss Randi E. , Bjørge Tone , Meyer Haakon E. , Blomhoff Rune , Tsugane Shoichiro , Sawada Norie , English Dallas R. , Eyles Darryl W. , Heath Alicia K. , Williamson Elizabeth J. , Manjer Jonas , Malm Johan , Almquist Martin , Marchand Loic Le , Haiman Christopher A. , Wilkens Lynne R. , Schenk Jeannette M. , Tangen Cathy M. , Black Amanda , Cook Michael B. , Huang Wen-Yi , Ziegler Regina G. , Martin Richard M. , Hamdy Freddie C. , Donovan Jenny L. , Neal David E. , Touvier Mathilde , Hercberg Serge , Galan Pilar , Deschasaux Mélanie , Key Timothy J. , Allen Naomi E. 
Published: November 2018

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 &lt; 0.001). However, this association varied by disease aggressiveness (Pheterogeneity = 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.