Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study

Hosen, M.I.; Sheikh, M.; Zvereva, M.; Scelo, G.; Forey, N.; Durand, G.; Voegele, C.; Poustchi, H.; Khoshnia, M.; Roshandel, G.; Sotoudeh, M.; Nikmanesh, A.; Etemadi, A.; Avogbe, P.H.; Chopard, P.; Delhomme, T.M.; Foll, M.; Manel, A.; Vian, E.; Weiderpass, E.; Kamangar, F.; Boffetta, P.; Pharaoh, P.D.; Dawsey, S.M.; Abnet, C.C.; Brennan, P.; McKay, J.; Malekzadeh, R.; Calvez-Kelm, F.L.

Авторы: Hosen Md Ismail, Sheikh Mahdi, Zvereva Maria, Scelo Ghislaine, Forey Nathalie, Durand Geoffroy, Voegele Catherine, Poustchi Hossein, Khoshnia Masoud, Roshandel Gholamreza, Sotoudeh Masoud, Nikmanesh Arash, Etemadi Arash, Avogbe Patrice Hodonou, Chopard Priscilia, Delhomme Tiffany Myriam, Foll Matthieu, Manel Arnaud, Vian Emmanuel, Weiderpass Elisabete, Kamangar Farin, Boffetta Paolo, Pharaoh Paul D., Dawsey Sanford M., Abnet Christian C., Brennan Paul, McKay James, Malekzadeh Reza, Calvez-Kelm Florence Le
Журнал: EBIOMEDICINE
Том: 53
Год издания: 2020
Номер статьи: 102643
DOI: 10.1016/j.ebiom.2020.102643
Аннотация: Background: Detecting pre-clinical bladder cancer (BC) using urinary biomarkers may provide a valuable opportunity for screening and management. Telomerase reverse transcriptase (TERT) promoter mutations detectable in urine have emerged as promising BC biomarkers.Methods: We performed a nested case-control study within the population-based prospective Golestan Cohort Study (50,045 participants, followed up to 14 years) and assessed TERT promoter mutations in baseline urine samples from 38 asymptomatic individuals who subsequently developed primary BC and 152 matched controls using a Next-Generation Sequencing-based single-plex assay (UroMuTERT) and droplet digital PCR assays.Findings: Results were obtained for 30 cases and 101 controls. TERT promoter mutations were detected in 14 pre-clinical cases (sensitivity 46·67%) and none of the controls (specificity 100·00%). At an estimated BC cumulative incidence of 0·09% in the cohort, the positive and negative predictive values were 100·00% and 99·95% respectively. The mutant allelic fractions decreased with the time interval from urine collection until BC diagnosis (p = 0·033) but the mutations were detectable up to 10 years prior to clinical diagnosis.Interpretation: Our results provide the first evidence from a population-based prospective cohort study of the potential of urinary TERT promoter mutations as promising non-invasive biomarkers for early detection of BC. Further studies should validate this finding and assess their clinical utility in other longitudinal cohorts.
Добавил в систему: Зверева Мария Эмильевна

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Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Studyстатья

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