Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Bonilla, Carolina; Lewis, Sarah; Martin, Richard; Donovan, Jenny; Hamdy, Freddie; Neal, David; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schleutker, Johanna; Nordestgaard, Børge; Travis, Ruth; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet; Blot, William; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel; Pandha, Hardev; Lathrop, Mark; Davey Smith, George;
• Is Part Of: BMC medicine. Volume 14:Issue 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: Boys -- Mendelian randomization -- Prostate cancer -- Puberty -- Tanner scale; Medicine -- Periodicals; 610.5
• DOI: 10.1186/s12916-016-0602-x
• Languages: English
• ISSNs: 1741-7015

Abstract

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.