PURPOSE: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. METHODS AND MATERIALS: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were within the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. RESULTS: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. CONCLUSIONS: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.
PURPOSE: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. METHODS AND MATERIALS: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancerpatients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were within the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. RESULTS: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. CONCLUSIONS: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.
Authors: Jennifer J Hu; James J Urbanic; L Doug Case; Cristiane Takita; Jean L Wright; Doris R Brown; Carl D Langefeld; Mark O Lively; Sandra E Mitchell; Anu Thakrar; David Bryant; Kathy Baglan; Jon Strasser; Luis Baez-Diaz; Glenn J Lesser; Edward G Shaw Journal: J Clin Oncol Date: 2018-07-10 Impact factor: 44.544
Authors: Jorge L Rodriguez-Gil; Cristiane Takita; Jean Wright; Isildinha M Reis; Wei Zhao; Brian E Lally; Jennifer J Hu Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-06-10 Impact factor: 4.254
Authors: Luis Alberto Henríquez-Hernández; Almudena Valenciano; Palmira Foro-Arnalot; María Jesús Alvarez-Cubero; José Manuel Cozar; José Francisco Suárez-Novo; Manel Castells-Esteve; Adriana Ayala-Gil; Pablo Fernández-Gonzalo; Montse Ferrer; Ferrán Guedea; Gemma Sancho-Pardo; Jordi Craven-Bartle; María José Ortiz-Gordillo; Patricia Cabrera-Roldán; Estefanía Herrera-Ramos; Pedro C Lara Journal: PLoS One Date: 2013-07-23 Impact factor: 3.240
Authors: Dae Sik Yang; Jung Ae Lee; Won Sup Yoon; Nam Kwon Lee; Young Je Park; Suk Lee; Chul Yong Kim; Gil Soo Son Journal: Biomed Res Int Date: 2016-08-07 Impact factor: 3.411
Authors: Salvatore Terrazzino; Sarah Cargnin; Letizia Deantonio; Carla Pisani; Laura Masini; Pier Luigi Canonico; Armando A Genazzani; Marco Krengli Journal: PLoS One Date: 2019-11-22 Impact factor: 3.240