Abstract 1407: Telomere length and melanoma survival
Authors: Rachakonda Sivaramakrishna , Srinivas Nalini , Garcia-Casado Zaida , Requena Celia , Nagore Eduardo , Kumar Rajiv 
Published: August 2018

Abstract
Telomeres at chromosomal ends are comprised of multiple short repeat sequences. In humans TTAGGG repeats account for 10-15 kb of double-stranded telomeres that end in single stranded G-rich tails of about 150-200 nucleotides. Telomeres in somatic cells undergo gradual shortening due to inherent limitations of DNA replication and limited levels of specialized enzyme telomerase. We previously reported an association between increased telomere length and risk of melanoma. In this study based on 1019 stage I and II cutaneous melanoma patients, we determined the effect of telomere length on patient survival. The telomere length was measured in DNA from peripheral blood cells using monochrome multiplex quantitative real-time PCR where telomere repeat copy number (T) was compared to a single-copy gene, albumin (S) and results presented as relative telomere length based on T/S ratio. A univariate Cox regression showed increased patient survival with increased telomere length (HR 0.65, 95% CI 0.42-1.00, P 0.05). With every decrease in 1 unit of telomere length the estimated odds of survival decreased by an approximate factor of 1.54 (95%CI 1.00-2.38). A model based on median distribution showed short rather than long telomere associated with poor survival with hazard ratio (HR) of 2.05 (95% confidence interval (CI) 1.33-3.16; log rank P 0.001); the model after adjustment with confounding factors including age at diagnosis showed a HR of 1.50 (95%CI 0.96-2.34). Stratification of patients based on median age showed statistically significant effect of decreased telomere length on poor survival in patients below the median age (HR 2.27 95%CI 1.09-4.27) but not in patients above the median age (HR 1.42 95%CI 0.82-2.46). Distribution of the patients into quantiles based on age showed the largest effect of decreased telomere length in patients younger than 30 years (HR 3.90 95%CI 1.28-11.93); the effect decreased with increasing age. Three single nucleotide polymorphisms, rs131178082, rs7726159 and rs6060627, previously shown to be associated with telomere length, were used to construct a weighted genetic score and paradoxically, the patients carrying the alleles associated with increased telomere length showed poor survival with shorter telomeres (HR 2.94 95%CI 1.54-5.62). Multivariate analysis that included, age, sex, outdoor life style, presence of actinic keratosis, number of nevi, tumor location, tumor stage, Breslow thickness and tumor ulceration showed a statistically significant association between composite genetic score and poor survival (HR 2.68 95%CI 1.24-5.80). Thus, the results from the study show that in contrast to association between melanoma risk and increased telomere length, the decreased telomere length associates with poor patient survival. The adverse effect on survival due to decreased telomere length was more pronounced in young rather than old patients and on the patients carrying genotypes for longer telomeres.
Citation Format: Sivaramakrishna Rachakonda, Nalini Srinivas, Zaida Garcia-Casado, Celia Requena, Eduardo Nagore, Rajiv Kumar. Telomere length and melanoma survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1407.