The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities

• Published in: Scientific reports Vol. 14; no. 1; p. 7706
• Main Authors: Huang, Ruotian, Bornman, M. S. Riana, Stricker, Phillip D., Simoni Brum, Ilma, Mutambirwa, Shingai B. A., Jaratlerdsiri, Weerachai, Hayes, Vanessa M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-04-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/589; 631/67/69; 692/4028/67/589; 692/4028/67/69; African ancestry; Aggressive disease; Base pairs; Blood; Chromosomes; Copy number; Genomes; Genomic Instability; Genomics; Health disparities; Health disparity; Health Inequities; Humanities and Social Sciences; Humans; Male; MSH2 protein; multidisciplinary; p53 Protein; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; PTEN protein; Science; Science (multidisciplinary); Telomere - genetics; Telomere - pathology; Telomere length; Telomeres; Tumors; Whole genome sequencing; African ancestry; Telomere length; Health disparity; Prostate cancer; Aggressive disease; Genomic instability
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-57566-1

The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer—implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability. Yet, no study has explored the role of telomere length (TL) with respect to ancestrally driven PCa health disparities. Patient- and technically-matched tumour-blood whole genome sequencing data for 179 ancestrally defined treatment naïve PCa patients (117 African, 62 European), we assessed for TL (blood and tumour) associations. We found shortened tumour TL to be associated with aggressive PCa presentation and elevated genomic instabilities, including percentage of genome alteration and copy number gains, in men of African ancestry. For European patients, tumour TL showed significant associations with PCa driver genes
PTEN
,
TP53
,
MSH2
,
SETBP1
and
DDX11L1
, while shorter blood TL (< 3200 base pairs) and tumour TL (< 2861 base pairs) were correlated with higher risk for biochemical recurrence. Concurring with previous studies linking TL to PCa diagnosis and/or prognosis, for the first time we correlated TL differences with patient ancestry with important implications for future treatments targeting telomere dysfunction.