144 Increased normal tissue telomere length is associated with decreased survival in melanoma patients

Abstract

Normal tissue telomere length (nTL) varies within the population, affected by inherited genetics and environmental risk factors. Previous work has investigated whether telomere length interplays with overall cancer survival. We aim to determine whether nTL was predictive of melanoma patient survival. Both normal and tumor tissue telomere lengths from The Cancer Genome Atlas (TCGA) skin melanoma dataset, along with other cancers, were obtained from supplementary data of the Barthel et al. study (Nat Genet 49, 349–357 (2017)), which were estimated from whole genome/whole exome sequencing data. Univariate and multivariate Cox proportional hazard regression models were applied to identify variables predicting survival, adjusting for age, gender and stage. nTL from individuals with melanoma did not demonstrate a normal distribution. The majority of patients (56%) had short nTL, defined as lower than one-third of the range, while only 8% of patients demonstrated nTL in the intermediate range. Analyzed as a continuous variable, increased nTL was negatively correlated with both overall (OS) and progression free survival (PFS) for melanoma patients (p=0.005, p=0.042), even after adjusting for age, gender and stage. In contrast, tumor telomere length did not demonstrate an association with survival. When stratified into groups, those with longer than median nTL showed worse OS and PFS compared to those with shorter nTL (p<0.001, p=0.007). We then expanded this analysis to 30 other cancers in TCGA. When stratified into groups, longer nTL correlated with worse OS within bladder and colorectal cancers. However, unlike melanoma, no other cancer demonstrated a significant correlation between nTL and OS when nTL was treated as a continuous variable. In conclusion, normal tissue telomere length may represent a prognostic marker for melanoma survival.