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Cancer Causes Control. 2015 Nov;26(11):1603-16. doi: 10.1007/s10552-015-0654-9. Epub 2015 Sep 19.

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.

Author information

1
School of Social and Community Medicine, University of Bristol, Bristol, UK. neil.davies@bristol.ac.uk.
2
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. neil.davies@bristol.ac.uk.
3
School of Social and Community Medicine, University of Bristol, Bristol, UK.
4
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
5
School of Clinical Sciences, University of Bristol, Bristol, BS10 5NB, UK.
6
Nuffield Department of Surgery, University of Oxford, Oxford, UK.
7
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
8
The Institute of Cancer Research, London, SM2 5NG, UK.
9
The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
10
Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK.
11
Institute of Population Health, University of Manchester, Manchester, UK.
12
Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, Australia.
13
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
14
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
15
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
16
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
17
Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
18
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark.
19
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
20
Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke's Hospital, Hills Road, Box 279, Cambridge, UK.
21
Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
22
Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, UK.
23
Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.
24
Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.
25
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
26
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
27
International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, MD, 20850, USA.
28
Mayo Clinic, Rochester, MN, USA.
29
Department of Urology, University Hospital Ulm, Ulm, Germany.
30
Institute of Human Genetics, University Hospital Ulm, Ulm, Germany.
31
Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA, 02115, USA.
32
Washington University, St. Louis, Missouri.
33
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
34
Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
35
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
36
Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
37
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
38
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL, USA.
39
Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431, Sofia, Bulgaria.
40
Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
41
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
42
Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
43
The University of Surrey, Guildford, Surrey, GU2 7XH, UK.
44
Commissariat à l'Energie Atomique, Center National de Génotypage, Evry, France.
45
McGill University-Génome Québec Innovation Centre, Montreal, Canada.
46
School of Social and Community Medicine, University of Bristol, Bristol, UK. richard.martin@bristol.ac.uk.
47
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. richard.martin@bristol.ac.uk.
48
Bristol Nutrition Biomedical Research Unit, National Institute for Health Research, Bristol, UK. richard.martin@bristol.ac.uk.

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.

KEYWORDS:

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

PMID:
26387087
PMCID:
PMC4596899
DOI:
10.1007/s10552-015-0654-9
[Indexed for MEDLINE]
Free PMC Article

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