Data from 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: March 2023

<div>Abstract<p>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)<sub>2</sub>D] 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)<sub>2</sub>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; <i>P</i> trend < 0.001). However, this association varied by disease aggressiveness (<i>P</i><sub>heterogeneity</sub> = 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)<sub>2</sub>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.</p>Significance:<p>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.</p></div>