dc.contributor.author | Bonilla, C | |
dc.contributor.author | Lewis, SJ | |
dc.contributor.author | Martin, RM | |
dc.contributor.author | Donovan, JL | |
dc.contributor.author | Hamdy, FC | |
dc.contributor.author | Neal, DE | |
dc.contributor.author | Eeles, R | |
dc.contributor.author | Easton, D | |
dc.contributor.author | Kote-Jarai, Z | |
dc.contributor.author | Al Olama, AA | |
dc.contributor.author | Benlloch, S | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | Wiklund, F | |
dc.contributor.author | Gronberg, H | |
dc.contributor.author | Haiman, CA | |
dc.contributor.author | Schleutker, J | |
dc.contributor.author | Nordestgaard, BG | |
dc.contributor.author | Travis, RC | |
dc.contributor.author | Pashayan, N | |
dc.contributor.author | Khaw, K-T | |
dc.contributor.author | Stanford, JL | |
dc.contributor.author | Blot, WJ | |
dc.contributor.author | Thibodeau, S | |
dc.contributor.author | Maier, C | |
dc.contributor.author | Kibel, AS | |
dc.contributor.author | Cybulski, C | |
dc.contributor.author | Cannon-Albright, L | |
dc.contributor.author | Brenner, H | |
dc.contributor.author | Park, J | |
dc.contributor.author | Kaneva, R | |
dc.contributor.author | Batra, J | |
dc.contributor.author | Teixeira, MR | |
dc.contributor.author | Pandha, H | |
dc.contributor.author | Lathrop, M | |
dc.contributor.author | Davey Smith, G | |
dc.contributor.author | PRACTICAL consortium, | |
dc.date.accessioned | 2016-11-09T11:41:28Z | |
dc.date.issued | 2016-04-04 | |
dc.identifier.citation | BMC medicine, 2016, 14 pp. 66 - ? | |
dc.identifier.issn | 1741-7015 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/198 | |
dc.identifier.eissn | 1741-7015 | |
dc.identifier.doi | 10.1186/s12916-016-0602-x | |
dc.description.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. | |
dc.format | Electronic | |
dc.format.extent | 66 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | PRACTICAL consortium | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | Neoplasm Staging | |
dc.subject | Odds Ratio | |
dc.subject | Risk Factors | |
dc.subject | Regression Analysis | |
dc.subject | Survival Analysis | |
dc.subject | Case-Control Studies | |
dc.subject | Random Allocation | |
dc.subject | Age of Onset | |
dc.subject | Puberty | |
dc.subject | Sexual Maturation | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Adolescent | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Mendelian Randomization Analysis | |
dc.subject | United Kingdom | |
dc.title | Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-03-16 | |
rioxxterms.versionofrecord | 10.1186/s12916-016-0602-x | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-04-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | BMC medicine | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.publication-status | Published | |
pubs.volume | 14 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Eeles, Rosalind | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |