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.
Scientific reports. 2024 Apr 02*** epublish ***
Ruotian Huang, M S Riana Bornman, Phillip D Stricker, Ilma Simoni Brum, Shingai B A Mutambirwa, Weerachai Jaratlerdsiri, Vanessa M Hayes
Ancestry and Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, 2006, Australia., School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, 0084, South Africa., Department of Urology, St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia., Endocrine and Tumor Molecular Biology Laboratory, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Department of Urology, Sefako Makgatho Health Science University, Dr George Mukhari Academic Hospital, Medunsa, 0208, South Africa., Ancestry and Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, 2006, Australia. .