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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Bonilla, C (Author) Other; Lewis, SJ (Author) Other; Martin, RM (Author) Other; Donovan, JL (Author) Other; Hamdy, FC (Author) Other; Neal, DE (Author) Other; Eeles, R (Author) Other; Easton, D (Author) Other; Kote Jarai, Z (Author) Other; Al Olama, AA (Author) Other; Benlloch, S (Author) Other; Muir, K (Author) Other; Giles, GG (Author) Other; Wiklund, F (Author) Other; Gronberg, H (Author) Other; Haiman, CA (Author) Other; Schleutker, J (Author) Other; Nordestgaard, BG (Author) Other; Travis, RC (Author) Other; Pashayan, N (Author) Other; Khaw, KT (Author) Other; Stanford, JL (Author) Other; Blot, WJ (Author) Other; Thibodeau, S (Author) Other; Maier, C (Author) Other; Kibel, AS (Author) Other; Cybulski, C (Author) Other; Cannon Albright, L (Author) Other; Brenner, H (Author) Other; Park, J (Author) Other; Kaneva, R (Author) Other; Batra, J (Author) Other; Manuel R Teixeira (Author) ICBAS; Pandha, H (Author) Other; Lathrop, M (Author) Other; Smith, GD (Author) Other

Journal

Title: BMC Medicine

Vol. 14

ISSN: 1741-7015

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 32 Citations

Scopus - 30 Citations

Other information

Authenticus ID: P-00K-DBR

DOI: 10.1186/s12916-016-0602-x

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11