ATM Polymorphisms and their Relationship to Radiation Toxicity in Breast Cancer Patients / Polimorfismos ATM e sua relação com a toxicidade por radiação em pacientes com câncer de mama

Satyaki Afonso Navinchandra, Pollyana Rodrigues Pimenta, João Lino Franco Borges, Antonio Márcio Teodoro Cordeiro Silva, Juliana Castro Dourado Pinezi, Yuri de Abreu Mendonça, Jose Claudio Casali da Rocha, Renata de Bastos Ascenço Soares

Resumo


Aims: The breast cancer is one of the most common types and it treatment brings complications such as skin, dermis and subcutaneous toxicity. Studies about genetic variations of patients are those that enable the identification of prognostic factors for treatment, generally based on greater risk of injury to healthy tissue. Study design: This study examined the association between single nucleotide polymorphisms (SNPs) of ATM gene in patients with breast cancer with adverse reactions presented in normal tissues as result of radiotherapy. Place and Duration of Study: The study was conduct at Pontifícia Universidade Católica de Goiás, and the patients were recruited at Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás, Radiotherapy Service. Methodology: We evaluated 76 patients, through a retrospective study, based on data contained in records and teletherapy records of patients with this cancer who underwent radiotherapy for at least 5 years. Polymorphisms of the ATM gene were analyzed by microarray technique. Results: The mean age of patients was 50 years and the total dose of radiation was an average of 50,21 Gy ranging from 45Gy to 50.4Gy. Regarding the late toxicities, patients analyzed showed a higher frequency of low-grade morbidities when compared to high grade. Nineteen patients interrupted the radiation therapy for any reason. Patients who have studied polymorphisms have no increased risk of developing acute toxicity changes of the skin. (P>.05). Patients presenting polymorphisms AX-8315255 (TTT insertion) (RR=11.0, 1.08 - 111.97, p=0.045) and rs56128736 (RR=11.0, 1.08 - 111.97, p=0.045) had an increased risk for developing late skin toxicity, but not at subcutaneous tract. Conclusion: ATM is a large gene with many variants documented. Association studies of these SNPs will be needed in larger sample groups to establish whether the single base variants or haplotypes of this gene may indeed contribute to the toxicity of normal tissue. Thus, the personalized treatment with ionizing radiation can be prescribed for patients decreasing complications and improving the effectiveness of treatment and quality of life of patients.

Palavras-chave


Breast cancer, ATM, adverse effects, radiotherapy, radiosensitivity

Texto completo:

PDF

Referências


Bubien V, Bonnet F, Dupiot-Chiron J, Barouk-Simonet E, Jones N, de Reynies A, MacGrogan G, Sevenet N, Letouzé E, Longy M. Combined tumor genomic profiling and exome sequencing in a breast cancer family implicates ATM in tumorigenesis: a proof of principle study. Genes Chromosomes Cancer. 2017; p. 1-33.

Ministry of Health. National Institute of Cancer (INCA), Brazil, 2018; [access in 12 March 2018]. Available in: http://www.inca.gov.br/estimativa/2018/

Apuri S. Neoadjuvant and Adjuvant Therapies for Breast Cancer. Southern Medical Journal. 2017;110(10):638-642.

WHO. International Agency for research on cancer. Press release, n. 233. 2017; [access in September 2017]. Available in: https://www.iarc.fr/en/media-centre/pr/2013/pdfs/pr223_E.pdf

Thorstenson YR, Shen P, Tusher VG, et al. Global analysis of ATM polymorphism reveals significant functional constraint. Am J Hum Genet 2001; vol.69, no.2, p.396–412.

Foray N, Colin C, Bourguignon M. 100 Years of Individual Radiosensitivity: How We Have Forgotten the Evidence. Radiology.2012;264(3):627–631.

Britel M, Bourguignon M, Foray N. The use of the term “radiosensitivity” through history of radiation: from clarity to confusion. International Journal of Radiation Biology. 2018;0(0):1–31.

Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008;322:881-8

Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits. Nat Rev Genet. 2009;10:241-51.

Hong H, Zhang W, Shen J, Su Z, Ning B, Han T, Perkins R, Shi L, Tong W. Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine.Sci China Life Sci. 2013 Feb ;56(2):110-8. doi: 10.1007/s11427-013-4439-7. [access in February 2018]. Available in: http://www.ncbi.nlm.nih.gov/pubmed/23393026

Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology, Nature 6. 2006; 702-713.

Nahum AE, Uzan J. (Radio)biological optimization of external-beam radiotherapy.Comput Math Methods Med. 2012 ;2012:329214.

Hummerich J, Werle-Schneider G, Popanda O, Celebi O, Chang-Claude J, Kropp S, Mayer C, Debus J, Bartsch H, Schmezer P. Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: a pilot study in prostate cancer patients receiving radiotherapy, Int J. Radiat. Biol. 82. 2006;593-604.

Svensson JP, Stalpers LJ, Esveldt-van Lange RE, Franken NA, Haveman J, Klein B, Turesson I, Vrieling H, Giphart-Gassler M. Analysis of gene expression using gene sets discriminates cancer patients with and without late radiation toxicity. PLoS Med. 2006; 3:422.

Gonnissen, A., Isebaert, S., Perneel, C., McKee, C. M., Verrill, C., Bryant, R. J., Muschel, R. J. Tissue microarray analysis indicates hedgehog signaling as a potential prognostic factor in intermediate-risk prostate cancer. BMC Cancer. 2017;17(1),634.

Onodera Y, Ichikawa Y, Giaccia AJ. Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells. 2017;5069–5085.

Elles LM, Uhlenbeck OC. Mutation of the arginine finger in the active site of Escherichia coli DbpA abolishes ATPase and helicase activity and confers a dominant slow growth phenotype. Nucleic Acids Res. 2008;36(1):41-50.

Wright JD, Lim C. Mechanism of DNA-binding loss upon single-point mutation in p53. J Biosci. 2007;32(5):827-39.

Koukouritaki SB, Poch MT, Henderson MC, Siddens LK, Krueger SK, VanDyke JE, Williams DE, Pajewski NM, Wang T, Hines RN. Identification and functional analysis of common human flavincontaining monooxygenase 3 genetic variants. J PharmacolExpTher. 2007;320(1):266-73.

De Cristofaro R, Carotti A, Akhavan S, Palla R, Peyvandi F, Altomare C, Mannucci PM. The natural mutation by deletion of Lys9 in the thrombin A-chain affects the pKa value of catalytic residues, the overall enzyme's stability and conformational transitions linked to Na+ binding. FEBS J. 2006;273(1):159-69.

Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, BhamraG,Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D,Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR. Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8

Melixetian M, Klein DK, Sørensen CS, Helin K. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat Cell Biol. 2009 Oct;11(10):1247-53.

Rashid OM, Takabe K. Sentinel Lymph Node Biopsy for Breast Cancer: Our Technique and Future Directions in Lymph Node Staging. J Nucl Med RadiatTher. 2012.

Ertan K, Linsler C, di Liberto A, Ong MF, Solomayer E, Endrikat J. Axillary ultrasound for breast cancer staging: an attempt to identify clinical/histopathological factors impacting diagnostic performance. Breast Cancer (Auckl). 2013;Jan;7:35–40.

Polymorphism Phenotyping v2 (PolyPhen-2). Avaiable in: (http://genetics.bwh.harvard.edu/pph2/. Access in Feb, 2018, Supplementary Software.

Weigelt B, Bi R, Kumar R, Blecua P, Mandelker DL, Geyer FC, Chenevix-Trench G. The Landscape of Somatic Genetic Alterations in Breast Cancers from ATM Germline Mutation Carriers. JNCI: Journal of the National Cancer Institute. 2018;110(March),1–5.

Pietrucha BM, Heropolitańska-Pliszka E, Wakulińska A, Skopczyńska H, Gatti RA, Bernatowska E. Ataxia-telangiectasia with hyper-IgM and Wilms tumor: fatal reaction to irradiation. J Pediatr Hematol Oncol. 2010;32(1):e28–e30.

Petereit, DG, Hahn LJ, Kanekar S, Boylan A, Bentzen SM, Ritter M, Moser AR. Prevalence of ATM Sequence Variants in Northern Plains American Indian Cancer Patients. Frontiers in Oncology, 2013;3(December),1–5. https://doi.org/10.3389/fonc.2013.00318




DOI: https://doi.org/10.34115/basrv4n5-029

Apontamentos

  • Não há apontamentos.