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

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.

SUBMITTER: Bonilla C

PROVIDER: S-EPMC4820939 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Bonilla Carolina C Lewis Sarah J SJ Martin Richard M RM Donovan Jenny L JL Hamdy Freddie C FC Neal David E DE Eeles Rosalind R Easton Doug D Kote-Jarai Zsofia Z Al Olama Ali Amin AA Benlloch Sara S Muir Kenneth K Giles Graham G GG Wiklund Fredrik F Gronberg Henrik H Haiman Christopher A CA Schleutker Johanna J Nordestgaard Børge G BG Travis Ruth C RC Pashayan Nora N Khaw Kay-Tee KT Stanford Janet L JL Blot William J WJ Thibodeau Stephen S Maier Christiane C Kibel Adam S AS Cybulski Cezary C Cannon-Albright Lisa L Brenner Hermann H Park Jong J Kaneva Radka R Batra Jyotsna J Teixeira Manuel R MR Pandha Hardev H Lathrop Mark M Davey Smith George G

BMC medicine 20160404

<h4>Background</h4>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) appro ...[more]

PMID: 27044414

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Project description:BackgroundPuberty is a critical period for bone mass accrual, and late puberty in boys is associated with reduced bone mass in adult men. The role of variations in pubertal timing within the normal range for adult fracture risk in men is, however, unknown. We, therefore, assessed the association between age at peak height velocity (PHV), an objective measure of pubertal timing, and fracture risk in adult men.Methods and findingsIn the BMI Epidemiology Study Gothenburg, 31,971 Swedish men born between January 1, 1945, and December 31, 1961, with detailed growth data (height and weight) available from centrally archived school healthcare records and the conscription register were followed until December 31, 2016. Age at PHV was calculated according to a modified infancy-childhood-puberty model, and fracture information was retrieved from the Swedish National Patient Register. The mean ± SD age at PHV was 14.1 ± 1.1 years. In total, 5,872 men (18.4%) sustained at least 1 fracture after 20 years of age and 5,731 men (17.9%) sustained a non-vertebral fracture after 20 years of age during a mean ± SD follow-up of 37.3 ± 11.7 years. Cox proportional hazards models adjusted for birth year and country of origin revealed that age at PHV was associated with the risk of any fracture and non-vertebral fracture. Participants with age at PHV in the highest tertile (after 14.5 years of age) were at greater risk of any fracture (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22, P < 0.001) and non-vertebral fracture (HR 1.16, 95% CI 1.09-1.24, P < 0.001) compared with those with age at PHV in the lowest tertile (at 13.6 years of age or younger). Additional adjustments for birthweight, childhood BMI, adult educational level, and young adult height did not attenuate the associations between age at PHV and adult fracture risk. Limitations of this study include the inability to adjust for important risk factors for fracture, inadequate power to assess the relation between pubertal timing and specific fracture types, and the limited generalizability to other populations.ConclusionsIn this study, we observed that late pubertal timing was associated with increased adult fracture risk in men. These findings suggest that information on pubertal timing might aid in the identification of those men at greatest risk of fracture.

Dataset Information

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

Publications

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

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