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

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. TravisDavid Neal, Nora Pashayan, Kay Tee Khaw, Janet L. Stanford, William J. Blot, Stephen N Thibodeau, Christiane Maier, Adam S. Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Park, Radka Kaneva, Jyotsna Batra, Manuel R. Teixeira, Hardev Pandha, consortium PRACTICAL consortium, Mark Lathrop, George Davey Smith, Daniel J Schaid

Research output: Contribution to journalArticle

29 Citations (Scopus)

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

Original languageEnglish (US)
Pages (from-to)1603-1616
Number of pages14
JournalCancer Causes and Control
Volume26
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Random Allocation
Prostatic Neoplasms
Mortality
Incidence
Odds Ratio
Genome-Wide Association Study
Adiposity
Uncertainty
Single Nucleotide Polymorphism
Epidemiologic Studies
Obesity
Alleles
Phenotype

Keywords

  • Body mass index
  • Height
  • Instrumental variables analysis
  • Mendelian randomization
  • Prostate cancer
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer Causes and Control, Vol. 26, No. 11, 01.11.2015, p. 1603-1616.

Research output: Contribution to journalArticle

Davies, NM, Gaunt, TR, Lewis, SJ, Holly, J, Donovan, JL, Hamdy, FC, Kemp, JP, Eeles, R, Easton, D, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Gronberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Neal, D, Pashayan, N, Khaw, KT, Stanford, JL, Blot, WJ, Thibodeau, SN, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, H, PRACTICAL consortium, C, Lathrop, M, Smith, GD & Schaid, DJ 2015, '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', Cancer Causes and Control, vol. 26, no. 11, pp. 1603-1616. https://doi.org/10.1007/s10552-015-0654-9
Davies, Neil M. ; Gaunt, Tom R. ; Lewis, Sarah J. ; Holly, Jeff ; Donovan, Jenny L. ; Hamdy, Freddie C. ; Kemp, John P. ; Eeles, Rosalind ; Easton, Doug ; Kote-Jarai, Zsofia ; Al Olama, Ali Amin ; Benlloch, Sara ; Muir, Kenneth ; Giles, Graham G. ; Wiklund, Fredrik ; Gronberg, Henrik ; Haiman, Christopher A. ; Schleutker, Johanna ; Nordestgaard, Børge G. ; Travis, Ruth C. ; Neal, David ; Pashayan, Nora ; Khaw, Kay Tee ; Stanford, Janet L. ; Blot, William J. ; Thibodeau, Stephen N ; Maier, Christiane ; Kibel, Adam S. ; Cybulski, Cezary ; Cannon-Albright, Lisa ; Brenner, Hermann ; Park, Jong ; Kaneva, Radka ; Batra, Jyotsna ; Teixeira, Manuel R. ; Pandha, Hardev ; PRACTICAL consortium, consortium ; Lathrop, Mark ; Smith, George Davey ; Schaid, Daniel J. / 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. In: Cancer Causes and Control. 2015 ; Vol. 26, No. 11. pp. 1603-1616.
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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",
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AU - Davies, Neil M.

AU - Gaunt, Tom R.

AU - Lewis, Sarah J.

AU - Holly, Jeff

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Kemp, John P.

AU - Eeles, Rosalind

AU - Easton, Doug

AU - Kote-Jarai, Zsofia

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Giles, Graham G.

AU - Wiklund, Fredrik

AU - Gronberg, Henrik

AU - Haiman, Christopher A.

AU - Schleutker, Johanna

AU - Nordestgaard, Børge G.

AU - Travis, Ruth C.

AU - Neal, David

AU - Pashayan, Nora

AU - Khaw, Kay Tee

AU - Stanford, Janet L.

AU - Blot, William J.

AU - Thibodeau, Stephen N

AU - Maier, Christiane

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Park, Jong

AU - Kaneva, Radka

AU - Batra, Jyotsna

AU - Teixeira, Manuel R.

AU - Pandha, Hardev

AU - PRACTICAL consortium, consortium

AU - Lathrop, Mark

AU - Smith, George Davey

AU - Schaid, Daniel J

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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

AB - 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

KW - Body mass index

KW - Height

KW - Instrumental variables analysis

KW - Mendelian randomization

KW - Prostate cancer

KW - Single nucleotide polymorphisms

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