Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119661
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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
1741-7015
Statement of
Responsibility: 
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 (http://creativecommons.org/licenses/by/4.0/), 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 (http://creativecommons.org/publicdomain/zero/1.0/) 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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