Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200,000 men in UK Biobank
Notice bibliographique
Résumé
Abstract Background Insulin-like growth factor-I (IGF-I) and testosterone have been implicated in prostate cancer aetiology. Using newly available data from a large prospective full-cohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we aimed to investigate the associations of circulating concentrations of IGF-I, sex hormone-binding globulin (SHBG), total and calculated free testosterone with prostate cancer risk. Patients and methods For prospective analyses of prostate cancer incidence and mortality, we studied 199,698 male UK Biobank participants using Cox proportional hazards models. Multivariable-adjusted hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample of up to 7,776 men. A 2-sample Mendelian randomization (MR) analysis of IGF-I and risk used genetic instruments identified from UK Biobank men and genetic outcome data from 79,148 cases and 61,106 controls from the PRACTICAL consortium. We used cis - and all ( cis and trans ) SNP MR approaches. Results After a mean follow-up of 6.9 years, 5,402 men were diagnosed with and 295 died from prostate cancer. Higher circulating IGF-I was associated with an elevated risk (HR per 5 nmol/L increment=1.09, 95% CI 1.05-1.12) and prostate cancer mortality (HR per 5 nmol/L increment=1.15,1.02-1.29) in observational analyses. Cis - and all SNPs MR analyses also supported the role of IGF-I in prostate cancer diagnosis ( cis -MR odds ratio per 5 nmol/L increment=1.34,1.07-1.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment=1.10,1.05-1.15), and higher SHBG was associated with a lower risk of prostate cancer (HR per 10 nmol/L increment=0.95,0.94-0.97), but neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. Conclusion(s) These findings implicate IGF-I and free testosterone in prostate cancer development and/or progression. Key message Prostate cancer is the second most common cancer in men, but modifiable risk factors have not been identified. Using large-scale prospective observational and genetic data we investigated the associations of circulating IGF-I, SHBG and testosterone with prostate cancer diagnosis and mortality. Our results implicate IGF-I and the sex hormones in prostate cancer development. Highlights Prostate cancer is the second most common cancer in men, but no modifiable risk factors are established. We examined the associations of circulating IGF-I, SHBG, total and free testosterone with prostate cancer risk in UK Biobank. Men with higher IGF-I had a higher risk of diagnosis and mortality. Mendelian randomization also supported a causal role. Men with higher free testosterone had a higher prostate cancer risk, and men with higher SHBG had a lower risk. The results implicate IGF-I and the sex hormones in prostate cancer development.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».