A collaborative analysis of individual participant data from 19 prospective studies assesses circulating Vitamin D and prostate cancer risk

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

doi:10.1158/0008-5472.CAN-18-2318

A collaborative analysis of individual participant data from 19 prospective studies assesses circulating Vitamin D and prostate cancer risk

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

Epidemiology

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26 Scopus citations

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 (mul-tivariable-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} ¼ 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase ¼ 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.

Original language	English (US)
Pages (from-to)	274-285
Number of pages	12
Journal	Cancer Research
Volume	79
Issue number	1
DOIs	https://doi.org/10.1158/0008-5472.CAN-18-2318
State	Published - Jan 1 2019

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Publisher Copyright:
©2018 American Association for Cancer Research.

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Travis, R. C., Perez-Cornago, A., Appleby, P. N., Albanes, D., Joshu, C. E., Lutsey, P. L., Mondul, A. M., Platz, E. A., Weinstein, S. J., Layne, T. M., Helzlsouer, K. J., Visvanathan, K., Palli, D., Peeters, P. H., Bueno-de-Mesquita, B., Trichopoulou, A., Gunter, M. J., Tsilidis, K. K., Sanchez, M. J., ... Allen, N. E. (2019). A collaborative analysis of individual participant data from 19 prospective studies assesses circulating Vitamin D and prostate cancer risk. Cancer Research, 79(1), 274-285. https://doi.org/10.1158/0008-5472.CAN-18-2318

Travis, RC, Perez-Cornago, A, Appleby, PN, Albanes, D, Joshu, CE, Lutsey, PL, Mondul, AM, Platz, EA, Weinstein, SJ, Layne, TM, Helzlsouer, KJ, Visvanathan, K, Palli, D, Peeters, PH, Bueno-de-Mesquita, B, Trichopoulou, A, Gunter, MJ, Tsilidis, KK, Sanchez, MJ, Olsen, A, Brenner, H, Schottker, B, Perna, L, Holleczek, B, Knekt, P, Rissanen, H, Yeap, BB, Flicker, L, Almeida, OP, Wong, YYE, Chan, JM, Giovannucci, EL, Stampfer, MJ, Ursin, G, Gislefoss, RE, Bjørge, T, Meyer, HE, Blomhoff, R, Tsugane, S, Sawada, N, English, DR, Eyles, DW, Heath, AK, Williamson, EJ, Manjer, J, Malm, J, Almquist, M, Le Marchand, L, Haiman, CA, Wilkens, LR, Schenk, JM, Tangen, CM, Black, A, Cook, MB, Huang, WY, Ziegler, RG, Martin, RM, Hamdy, FC, Donovan, JL, Neal, DE, Touvier, M, Hercberg, S, Galan, P, Deschasaux, M, Key, TJ & Allen, NE 2019, 'A collaborative analysis of individual participant data from 19 prospective studies assesses circulating Vitamin D and prostate cancer risk', Cancer Research, vol. 79, no. 1, pp. 274-285. https://doi.org/10.1158/0008-5472.CAN-18-2318

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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 (mul-tivariable-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 (Pheterogeneity ¼ 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase ¼ 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.",

author = "Travis, {Ruth C.} and Aurora Perez-Cornago and Appleby, {Paul N.} and Demetrius Albanes and Joshu, {Corinne E.} and Lutsey, {Pamela L.} and Mondul, {Alison M.} and Platz, {Elizabeth A.} and Weinstein, {Stephanie J.} and Layne, {Tracy M.} and Helzlsouer, {Kathy J.} and Kala Visvanathan and Domenico Palli and Peeters, {Petra H.} and Bas Bueno-de-Mesquita and Antonia Trichopoulou and Gunter, {Marc J.} and Tsilidis, {Konstantinos K.} and Sanchez, {Maria Jose} and Anja Olsen and Hermann Brenner and Ben Schottker and Laura Perna and Bernd Holleczek and Paul Knekt and Harri Rissanen and Yeap, {Bu B.} and Leon Flicker and Almeida, {Osvaldo P.} and Wong, {Yuen Yee Elizabeth} and Chan, {June M.} and Giovannucci, {Edward L.} and Stampfer, {Meir J.} and Giske Ursin and Gislefoss, {Randi E.} and Tone Bj{\o}rge and Meyer, {Haakon E.} and Rune Blomhoff and Shoichiro Tsugane and Norie Sawada and English, {Dallas R.} and Eyles, {Darryl W.} and Heath, {Alicia K.} and Williamson, {Elizabeth J.} and Jonas Manjer and Johan Malm and Martin Almquist and {Le Marchand}, Loic and Haiman, {Christopher A.} and Wilkens, {Lynne R.} and Schenk, {Jeannette M.} and Tangen, {Cathy M.} and Amanda Black and Cook, {Michael B.} and Huang, {Wen Yi} and Ziegler, {Regina G.} and Martin, {Richard M.} and Hamdy, {Freddie C.} and Donovan, {Jenny L.} and Neal, {David E.} and Mathilde Touvier and Serge Hercberg and Pilar Galan and Melanie Deschasaux and Key, {Timothy J.} and Allen, {Naomi E.}",

note = "Publisher Copyright: {\textcopyright}2018 American Association for Cancer Research.",

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doi = "10.1158/0008-5472.CAN-18-2318",

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T1 - A collaborative analysis of individual participant data from 19 prospective studies assesses circulating Vitamin D and prostate cancer risk

AU - Travis, Ruth C.

AU - Perez-Cornago, Aurora

AU - Appleby, Paul N.

AU - Albanes, Demetrius

AU - Joshu, Corinne E.

AU - Lutsey, Pamela L.

AU - Mondul, Alison M.

AU - Platz, Elizabeth A.

AU - Weinstein, Stephanie J.

AU - Layne, Tracy M.

AU - Helzlsouer, Kathy J.

AU - Visvanathan, Kala

AU - Palli, Domenico

AU - Peeters, Petra H.

AU - Bueno-de-Mesquita, Bas

AU - Trichopoulou, Antonia

AU - Gunter, Marc J.

AU - Tsilidis, Konstantinos K.

AU - Sanchez, Maria Jose

AU - Olsen, Anja

AU - Brenner, Hermann

AU - Schottker, Ben

AU - Perna, Laura

AU - Holleczek, Bernd

AU - Knekt, Paul

AU - Rissanen, Harri

AU - Yeap, Bu B.

AU - Flicker, Leon

AU - Almeida, Osvaldo P.

AU - Wong, Yuen Yee Elizabeth

AU - Chan, June M.

AU - Giovannucci, Edward L.

AU - Stampfer, Meir J.

AU - Ursin, Giske

AU - Gislefoss, Randi E.

AU - Bjørge, Tone

AU - Meyer, Haakon E.

AU - Blomhoff, Rune

AU - Tsugane, Shoichiro

AU - Sawada, Norie

AU - English, Dallas R.

AU - Eyles, Darryl W.

AU - Heath, Alicia K.

AU - Williamson, Elizabeth J.

AU - Manjer, Jonas

AU - Malm, Johan

AU - Almquist, Martin

AU - Le Marchand, Loic

AU - Haiman, Christopher A.

AU - Wilkens, Lynne R.

AU - Schenk, Jeannette M.

AU - Tangen, Cathy M.

AU - Black, Amanda

AU - Cook, Michael B.

AU - Huang, Wen Yi

AU - Ziegler, Regina G.

AU - Martin, Richard M.

AU - Hamdy, Freddie C.

AU - Donovan, Jenny L.

AU - Neal, David E.

AU - Touvier, Mathilde

AU - Hercberg, Serge

AU - Galan, Pilar

AU - Deschasaux, Melanie

AU - Key, Timothy J.

AU - Allen, Naomi E.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 (mul-tivariable-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 (Pheterogeneity ¼ 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase ¼ 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.

AB - 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 (mul-tivariable-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 (Pheterogeneity ¼ 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase ¼ 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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A collaborative analysis of individual participant data from 19 prospective studies assesses circulating Vitamin D and prostate cancer risk

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