Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort - Institut de Biologie François JACOB Access content directly
Journal Articles BMC Medicine Year : 2016

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

William J Blot
  • Function : Author
Stephen Thibodeau
  • Function : Author
Adam S Kibel
  • Function : Author
Cezary Cybulski
  • Function : Author
Lisa Cannon-Albright
  • Function : Author
Jong Park
  • Function : Author
Radka Kaneva
  • Function : Author
Hardev Pandha
  • Function : Author
The Practical Consortium
  • Function : Author

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.
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cea-04551279 , version 1 (18-04-2024)

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Carolina Bonilla, Sarah J Lewis, Richard M Martin, Jenny L Donovan, Freddie C Hamdy, et al.. Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort. BMC Medicine, 2016, 14 (1), pp.66. ⟨10.1186/s12916-016-0602-x⟩. ⟨cea-04551279⟩
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