Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study.
Abstract
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. FUNDING: French Cancer League, World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, the International Agency for Research on Cancer, and the U.S. National Cancer Institute.
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BibTeX
@article{hosen2026urinary,
title = {{Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study.}},
author = {Md Ismail Hosen and Mahdi Sheikh and Maria Zvereva and Ghislaine Scelo and Nathalie Forey and Geoffroy Durand and Catherine Voegele and Hossein Poustchi and Masoud Khoshnia and Gholamreza Roshandel and Masoud Sotoudeh and Arash Nikmanesh and Arash Etemadi and Patrice Hodonou Avogbe and Priscilia Chopard and Tiffany Myriam Delhomme and Matthieu Foll and Arnaud Manel and Emmanuel Vian and Elisabete Weiderpass and Farin Kamangar and Paolo Boffetta and Paul D Pharaoh and Sanford M Dawsey and Christian C Abnet and Paul Brennan and James Mckay and Reza Malekzadeh and Florence Le Calvez-Kelm},
journal = {EBioMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.ebiom.2020.102643},
url = {https://hal.science/hal-05842047v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study.
AU - Md Ismail Hosen
AU - Mahdi Sheikh
AU - Maria Zvereva
AU - Ghislaine Scelo
AU - Nathalie Forey
AU - Geoffroy Durand
AU - Catherine Voegele
AU - Hossein Poustchi
AU - Masoud Khoshnia
AU - Gholamreza Roshandel
AU - Masoud Sotoudeh
AU - Arash Nikmanesh
AU - Arash Etemadi
AU - Patrice Hodonou Avogbe
AU - Priscilia Chopard
AU - Tiffany Myriam Delhomme
AU - Matthieu Foll
AU - Arnaud Manel
AU - Emmanuel Vian
AU - Elisabete Weiderpass
AU - Farin Kamangar
AU - Paolo Boffetta
AU - Paul D Pharaoh
AU - Sanford M Dawsey
AU - Christian C Abnet
AU - Paul Brennan
AU - James Mckay
AU - Reza Malekzadeh
AU - Florence Le Calvez-Kelm
PY - 2026
DA - 2026/10/28
JO - EBioMedicine
DO - 10.1016/j.ebiom.2020.102643
UR - https://hal.science/hal-05842047v1
AB - 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. FUNDING: French Cancer League, World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, the International Agency for Research on Cancer, and the U.S. National Cancer Institute.
SN - 2352-3964
ER -