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The authors declare that they have no conflict of interest to disclose.
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Radiotherapy and Oncology
Association of single nucleotide polymorphisms at HSPB1 rs7459185 and TGFB1 rs11466353 with LDN 193189 esophagitis in lung cancer
Blas David Delgado a,1, María Valle Enguix-Riego a,b,1, Jon Cacicedo Fernández de Bobadilla c, Daniel Herrero Rivera d, Jose María Nieto-Guerrero Gómez e, Juan Manuel Praena-Fernández f, Eleonor Rivin del Campo g, María José Ortiz Gordillo a,b, María del Carmen Fernandez Fernandez a,b, Jose Luis Lopez Guerra a,b,⇑
a Department of Radiation Oncology, University Hospital Virgen del Rocío; b Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain; c Department of Radiation Oncology, Cruces University Hospital, Barakaldo; d Department of Medical Oncology, University Hospital Virgen del Rocío, Seville; e Department of Radiation Oncology, Ciudad Real; f Methodology Unit, University Hospital Virgen del Rocío, Seville, Spain; and g Department of Radiation Oncology, Tenon University Hospital, Paris, France
Single nucleotide polymorphisms
Background and purpose: Radiochemotherapy (RCT) success in lung cancer (LC) can be limited due to the onset of adverse effects in the adjacent normal tissue such as radiation-induced esophageal toxicity (RIET). Therefore, specific biomarkers to customize the RCT dose administration and esophageal toxicity prediction are necessary to improve treatment effectiveness. r> Materials and methods: 247 LC patients prospectively recruited between 2012 and 2016 from 3 institu-tions were genotyped for 7 SNPs along TGFB1 and HSPB1 genes seeking an association with RIET risk development. Kaplan–Meier cumulative probability and Cox proportional hazards analyses were used to evaluate the effect of TGFB1 and HSPB1 genotypes on such risk.
Conclusion: The presence of different rs7459185/rs11466353 genotypes in LC patients associated with RIET risk and may be useful biomarkers along with other risk factors for guiding therapy intensity in an individualized therapy.
Lung cancer (LC) ranks among the leading causes of death asso-ciated with cancer worldwide due to its high incidence and mortal-ity rates. This poses a significant challenge to the health system and a dire economic problem . For advanced (non-metastatic) LC and inoperable cases, radiation therapy (RT) given with chemotherapy is the first-line treatment. RT with curative inten-tion aims to accomplish a beneficial therapeutic index, leading malignant cells to lose their clonogenicity by cell death induction through DNA damage, with the goal of achieving uncomplicated local regional control [2,3]. However, in many cases, the normal
⇑ Corresponding author at: Department of Radiation Oncology, Virgen del Rocío University Hospital, Manuel Siurot avenue, s/n. 41013, Seville Spain.
E-mail address: [email protected] (J.L. Lopez Guerra).
1 The first two authors contributed equally to this work.
adjacent tissue’s radiation tolerance limits the administered radia-tion dose, thus RT treatment is often accompanied by adverse reac-tions such as radiation-induced esophageal toxicity (RIET) and radio-induced pneumonitis, affecting treatment efficacy and nega-tively impairing patient’s quality of life [4–6].
RIET can be classified as acute, which usually occurs within 90 days after the completion of treatment and is normally addressed by conservative supportive care, or late, which is more persistent and troublesome with a median onset time of 6 months . The development of different techniques such as three-dimensional conformal radiation therapy, Intensity-Modulated Radiation Therapy (IMRT), Volumetric Modulated Arc Therapy (VMAT), or image-guided radiation therapy (IGRT) has improved the aspects commented above [8,9]. Nevertheless, most patients present acute esophageal toxicity as a response to esophageal
162 SNPs associated with esophagitis in lung cancer