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

  • Carolina Bonilla (Creator)
  • Sarah Lewis (Creator)
  • Richard Martin (Creator)
  • Jenny L Donovan (Creator)
  • Freddie C. Hamdy (Creator)
  • David E Neal (Creator)
  • Rosalind Eeles (Creator)
  • Doug Easton (Creator)
  • Zsofia Kote-Jarai (Creator)
  • Ali Amin Al Olama (Creator)
  • Sara Benlloch (Creator)
  • Kenneth Muir (Creator)
  • Graham Giles (Creator)
  • Fredrik Wiklund (Creator)
  • Henrik Gronberg (Creator)
  • Christopher A. Haiman (Creator)
  • Johanna Schleutker (Creator)
  • Børge G Nordestgaard (Creator)
  • Ruth C. Travis (Creator)
  • Nora Pashayan (Creator)
  • Kay-Tee Khaw (Creator)
  • Janet L. Stanford (Creator)
  • William Blot (Creator)
  • Stephen N. Thibodeau (Creator)
  • Christiane Maier (Creator)
  • Adam S Kibel (Creator)
  • Lisa Cannon-Albright (Creator)
  • Hermann Brenner (Creator)
  • Jong Park (Creator)
  • Radka Kaneva (Creator)
  • Jyotsna Batra (Creator)
  • Manuel R Teixeira (Creator)
  • Hardev Pandha (Creator)
  • Mark Lathrop (Creator)
  • George Davey Smith (Creator)



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.
Date made available4 Apr 2016


  • Boys
  • Mendelian randomization
  • Prostate cancer
  • Puberty
  • Tanner scale
  • Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort

    Bonilla, C., Lewis, S. J., Martin, R. M., Donovan, J. L., Hamdy, F. C., Neal, D. E., Eeles, R., Easton, D., Kote-jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Gronberg, H., Haiman, C. A., Schleutker, J., Nordestgaard, B. G., Travis, R. C., Pashayan, N., & 16 othersKhaw, K., Stanford, J. L., Blot, W. J., Thibodeau, S., Maier, C., Kibel, A. S., Cybulski, C., Cannon-albright, L., Brenner, H., Park, J., Kaneva, R., Batra, J., Teixeira, M. R., Pandha, H., Lathrop, M. & Davey Smith, G., 1 Dec 2016, In: BMC Medicine. 14, 1

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    Open Access

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