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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

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

Revista

Título: BMC Medicine

Vol. 14

ISSN: 1741-7015

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 32 Citações

Scopus - 30 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11