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

N M Davies, T R Gaunt, S J Lewis, J Holly, J L Donovan, F C Hamdy, J P Kemp, R Eeles, D Easton, Z Kote-Jarai, A A Al Olama, S Benlloch, K Muir, G G Giles, F Wiklund, H Gronberg, C A Haiman, J Schleutker, B G Nordestgaard, R C TravisD Neal, N Pashayan, K T Khaw, J L Stanford, W J Blot, S Thibodeau, C Maier, A S Kibel, C Cybulski, L Cannon-Albright, H Brenner, J Park, R Kaneva, J Batra, M R Teixeira, H Pandha, M Lathrop, G D Smith, R M Martin

    Research output: Contribution to journalArticlepeer-review

    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
    Pages (from-to)1603-16
    Number of pages1586
    JournalCancer Causes Control
    Volume26
    Issue number11
    DOIs
    Publication statusPublished - 2015

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