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Type: Journal article
Title: Pubertal development and prostate cancer risk: mendelian randomization study in a population-based cohort
Author: Bonilla, C.
Lewis, S.
Martin, R.
Donovan, J.
Hamdy, F.
Neal, D.
Eeles, R.
Easton, D.
Kote-Jarai, Z.
Al Olama, A.
Benlloch, S.
Muir, K.
Giles, G.
Wiklund, F.
Gronberg, H.
Haiman, C.
Schleutker, J.
Nordestgaard, B.
Travis, R.
Pashayan, N.
et al.
Citation: BMC Medicine, 2016; 14(1):66
Publisher: BMC
Issue Date: 2016
ISSN: 1741-7015
Statement of
Carolina Bonilla, Sarah J. Lewis, Richard M. Martin, Jenny L. Donovan, Freddie C. Hamdy ...Wayne D. Tilley ... et al.
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
Rights: © 2016 Bonilla et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
RMID: 0030105299
DOI: 10.1186/s12916-016-0602-x
Appears in Collections:Medicine publications

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