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Cancer Causes & Control
Published in: Cancer Causes & Control 11/2015

Open Access 01-11-2015 | Original paper

The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Authors: Neil M. Davies, Tom R. Gaunt, Sarah J. Lewis, Jeff Holly, Jenny L. Donovan, Freddie C. Hamdy, John P. Kemp, Rosalind Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A. Haiman, Johanna Schleutker, Børge G. Nordestgaard, Ruth C. Travis, David Neal, Nora Pashayan, Kay-Tee Khaw, Janet L. Stanford, William J. Blot, Stephen Thibodeau, Christiane Maier, Adam S. Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Park, Radka Kaneva, Jyotsna Batra, Manuel R. Teixeira, Hardev Pandha, Mark Lathrop, George Davey Smith, Richard M. Martin, PRACTICAL consortium

Published in: Cancer Causes & Control | Issue 11/2015

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Abstract

Background

Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.

Methods

We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.

Results

The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03).

Conclusions

We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.
Appendix
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Metadata
Title
The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium
Authors
Neil M. Davies
Tom R. Gaunt
Sarah J. Lewis
Jeff Holly
Jenny L. Donovan
Freddie C. Hamdy
John P. Kemp
Rosalind Eeles
Doug Easton
Zsofia Kote-Jarai
Ali Amin Al Olama
Sara Benlloch
Kenneth Muir
Graham G. Giles
Fredrik Wiklund
Henrik Gronberg
Christopher A. Haiman
Johanna Schleutker
Børge G. Nordestgaard
Ruth C. Travis
David Neal
Nora Pashayan
Kay-Tee Khaw
Janet L. Stanford
William J. Blot
Stephen Thibodeau
Christiane Maier
Adam S. Kibel
Cezary Cybulski
Lisa Cannon-Albright
Hermann Brenner
Jong Park
Radka Kaneva
Jyotsna Batra
Manuel R. Teixeira
Hardev Pandha
Mark Lathrop
George Davey Smith
Richard M. Martin
PRACTICAL consortium
Publication date
01-11-2015
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 11/2015
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-015-0654-9

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