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

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Bonilla, C and Lewis, SJ and Martin, RM and Donovan, JL and Hamdy, FC and Neal, DE 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 Pashayan, N and Khaw, KT and Stanford, JL and Blot, WJ and Thibodeau, S and Maier, C and Kibel, AS 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 Davey Smith, G and Fitzgerald, LM and The PRACTICAL consortium, Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort, BMC Medicine, 14 Article 66. ISSN 1741-7015 (2016) [Refereed Article]


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Copyright 2016 Bonilla et al. Licensed under Creative Cohttps://creativecommons.org/licenses/by/4.0/mmons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1186/s12916-016-0602-x

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.

Item Details

Item Type:Refereed Article
Keywords:Boys, Mendelian randomization, Prostate cancer, Puberty, Tanner scale
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
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:114203
Year Published:2016
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-02-08
Last Modified:2017-11-06
Downloads:4 View Download Statistics

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