Abstract P3-03-06: Telomerase polymorphism and breast cancer

Abstract

Abstract Introduction: Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. The minimum essential components of telomerase are the catalytic subunit, telomerase reverse transcriptase (TERT), and a non- coding RNA (TERC); TERT reverse transcribes telomere DNA using TERC as the template (1). Given the fundamental role of TERT in oncogenesis, polymorphisms of genes related to telomerase may influence the expression levels of this enzyme, influencing the host's susceptibility to tumor progression and metastasis [2,3]. Some studies have linked these polymorphisms with susceptibility and/or survival of patients with breast cancer [2,4,5,6]. In this work, we analyzed a region in the second intron of the gene TERT, located in chromosome 5p15.33, by sequencing, in order to find mutations associated with clinical aspects. The DNA of 65 patients with breast cancer were evaluated. Methodology: The population consisted of breast cancer patients who accepted to participate in the study, attended from March 2015 to September 2016 at a public hospital (HUB) and a private center for cancer treatment (Cettro®), both in Brasília city – Brazil. Standard DNA extraction from blood samples was performed by dehydration and precipitation with saturated NaCl solution. The concentration and purity of the DNA were determined by spectrophotometry using the NanoDrop One equipment® (Themo Scientific, Madison, USA). The region of interest was amplified by conventional PCR. The primer sequences were: F: 5'-ATG CGA CAG TTC GTG GCT CA-3 'and R: 5'-ATC CCC TGG CAC TGG ACG TA-3'. The sequencing was performed in the AB 3500 Genetic Analyzer® (Applied Biosystems). Data were analyzed by using software Chromas Lite ® (2.01, Technelysium Pty Ltd.) and the BLAST (NCBI - http://blast.ncbi.nlm.nih.gov/Blast.cgi). GraphPad Prism software version 7.02 was used for statistical analyzes. Results and Conclusion: A total of 65 patients were selected for DNA analysis. We identified a recurrent mutation (C>T) among them. The allelic frequencies were 0,79 for C and 0,21 for T. Only three patients had genotype TT, but 21 were heterozygous (CT). This polymorphism was significantly associated with tumor grade, the presence of T allele were implicated in more aggressive (grade 3) tumors (p=0.028, chi-square test). Those patients whith genotype CT were at greater risk them others whith CC genotype of having high grade (3) breast tumors (odds ratio = 6.13, 95% confidence interval 1.46, 25.74; relative risk 1.9, 95% confidence interval 1.02, 3.59). Citation Format: Alvares MM, Rodrigues KS, Matos JN, Oliveira DM. Telomerase polymorphism and breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-03-06.