Abstract 1643: Relative telomere length analysis in breast cancer patients with TP53 p.R337H and XAF1 p.E134* germline variants
Authors: Okano Larissa M. , Bortoletto Stéfanne M. , Paraizo Mariana , Fonseca Aline S. , Figueiredo Bonald C. , Ribeiro Enilze M F. , Centa Ariana , Cavalli Luciane R. 
Published: March 2024

Abstract
Background: Telomere deregulation is one of the forms of genomic instability, an enabling characteristic of the cancer hallmarks. The TP53 gene plays a fundamental role in genome integrity maintenance by controlling cell cycle, apoptosis, senescence, and DNA repair. The germline variant TP53 p.R337H, a low penetrance variant, has been described in several types of cancer, including sporadic and familial breast cancer. The XAF1 p.E134*, a germline variant of the tumor-suppressor gene X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), is a genetic modifier of p53 function and was found to co-segregate with TP53 p.R337H variant on the 17p13 region. The main objective of this study was to determine the impact of the TP53 p.R337H and XAF1 p.E134* germline variants on the relative telomere length (RTL) in breast cancer patients.
Materials and methods: Peripheral blood samples from three distinct groups of patients were collected: patients with breast cancer (BC; n=56) (test group), patients with other types of cancer (non-BC; n=59), and individuals without cancer and cancer family history (non-CA; n=100) (control groups). The samples were genotyped for the TP53 p.R337H and XAF1 p.E134* variants. The RTL analysis was performed by RT-qPCR, using primers for the TEL gene (T) and 36B4 gene (S) (reference) and calculated based on the T/S ratio.
Results: BC cases with TP53 p.R337H variant exhibited higher RTL compared to cases without the variant. No RTL differences were observed for the XAF1p.E134* variant or for the concomitant presence of these variants. However, in the non-BC cases higher RTL were observed in all the cases positive for the variants compared to the negative cases. The same was observed for the BC and non-BC cancer cases combined (CA cases). In the non-CA cases no difference in the RTL was observed in relation to the variants. The stratification of the cases by age (≤ or &gt;45 years old), showed that the TP53 p.R337H variant was significantly associated to longer telomeres in the BC and CA patients across all ages. XAF1 p.E134* showed age-dependent effects, with longer telomeres in BC and CA patients ≤ 45 years. Non-BC cases had similar results.
Conclusion: This study indicates that TP53 p.R337H significantly impacts telomere length in BC cases, while XAF1 p.E134* shows age-dependent effects. Despite the observed variability, these findings highlight an association between these germline variants and telomere length regulation. Further research is needed to elucidate the functional impact and underlying mechanisms of these variants, particularly in the context of breast cancer.
Citation Format: Larissa M. Okano, Stéfanne M. Bortoletto, Mariana Paraizo, Aline S. Fonseca, Bonald C. Figueiredo, Enilze M F. Ribeiro, Ariana Centa, Luciane R. Cavalli. Relative telomere length analysis in breast cancer patients with TP53 p.R337H and XAF1 p.E134* germline variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1643.