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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

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Davies, NM and Gaunt, TR and Lewis, SJ and Holly, J and Donovan, JL and Hamdy, FC and Kemp, JP and Eeles, R and Easton, D and Kote-Jarai, Z and Al Olama, AA and Benlloch, S and Muir, K and Giles, GG and Wiklund, F and Gronberg, H and Haiman, CA and Schleutker, J and Nordestgaard, BG and Travis, RC and Neal, D and Pashayan, N and Khaw, K-T and Stanford, JL and Blot, WJ and Thibodeau, S and Maier, C and Kibel, A and Cybulski, C and Cannon-Albright, L and Brenner, H and Park, J and Kaneva, R and Batra, J and Teixeira, MR and Pandha, H and Lathrop, M and Smith, GD and Martin, RM, PRACTICAL consortium, 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, 26, (11) pp. 1603-1616. ISSN 0957-5243 (2015) [Refereed Article]


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Copyright 2015 The Authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1007/s10552-015-0654-9

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.

Item Details

Item Type:Refereed Article
Keywords:prostate cancer, height, BMI
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
ID Code:104094
Year Published:2015
Web of Science® Times Cited:33
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-11-03
Last Modified:2016-12-19
Downloads:208 View Download Statistics

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