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]
Copyright 2016 Bonilla et al. Licensed under Creative Cohttps://creativecommons.org/licenses/by/4.0/mmons Attribution 4.0 International (CC BY 4.0)
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 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 Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Cancer and Related Disorders|
|Author:||Fitzgerald, LM (Dr Liesel Fitzgerald)|
|Web of Science® Times Cited:||7|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||11 View Download Statistics|
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