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BMC Med. 2016 Apr 4;14:66. doi: 10.1186/s12916-016-0602-x.

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort.

Author information

1
School of Social and Community Medicine, University of Bristol, Bristol, UK.
2
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
3
School of Social and Community Medicine, University of Bristol, Bristol, UK. richard.martin@bristol.ac.uk.
4
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. richard.martin@bristol.ac.uk.
5
National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK. richard.martin@bristol.ac.uk.
6
Nuffield Department of Surgery, University of Oxford, Oxford, UK.
7
Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Box 279, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
8
The Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG Surrey, UK.
9
The Royal Marsden NHS Foundation Trust, Fulham and Sutton, London and Surrey, UK.
10
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
11
University of Warwick, Coventry, UK.
12
Institute of Population Health, The University of Manchester, Manchester, M13 9PL, UK.
13
The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004, Australia.
14
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
15
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
16
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
17
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
18
Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
19
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK-2730, Denmark.
20
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
21
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
22
Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.
23
Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.
24
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
25
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
26
International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, MD, 20850, USA.
27
Mayo Clinic, Rochester, MN, USA.
28
Department of Urology, University Hospital Ulm, Ulm, Germany.
29
Institute of Human Genetics, University Hospital Ulm, Ulm, Germany.
30
Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street - ASB II-3, Boston, MA, 02115, USA.
31
Washington University, St Louis, MO, USA.
32
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
33
Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
34
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
35
Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
36
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
37
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL, USA.
38
Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University-Sofia, 2 Zdrave St., Sofia, 1431, Bulgaria.
39
Australian Prostate Cancer Research Centre - Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
40
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
41
Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
42
The University of Surrey, Guildford, Surrey, GU2 7XH, UK.
43
Commissariat à l'Energie Atomique, Center National de Génotypage, Evry, France.
44
McGill University-Génome Québec Innovation Centre, Montreal, Canada.

Abstract

BACKGROUND:

Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach.

METHODS:

We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample.

RESULTS:

In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade.

CONCLUSIONS:

Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.

KEYWORDS:

Boys; Mendelian randomization; Prostate cancer; Puberty; Tanner scale

PMID:
27044414
PMCID:
PMC4820939
DOI:
10.1186/s12916-016-0602-x
[Indexed for MEDLINE]
Free PMC Article

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