Cristina Pérez-Ramírez1, Marisa Cañadas-Garre2, Ahmed Alnatsha3, Miguel Ángel Molina4, Ana I Robles5, Eduardo Villar6, Juan Ramón Delgado7, María José Faus-Dáder8, Miguel Ángel Calleja-Hernández9. 1. Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, Spain; Department of Biochemistry, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, s/n, 18071 Granada, Spain. Electronic address: cperezramirez87@gmail.com. 2. Centre for Public Health, Queen's University of Belfast c/o Regional Genetics Centre, Level A, Tower Block, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, United Kingdom. Electronic address: marisacgarre@gmail.com. 3. Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, Spain; Department of Molecular Medicine, Faculty of Medicine, University of Tübingen, Geissweg 5, 72076 Tübingen, Germany. Electronic address: r.j.b-man@hotmail.com. 4. Pangaea Biotech, S.L., Hospital Universitario Quirón Dexeus, C/ Sabino Arana, 5-19, 08028 Barcelona, Spain. Electronic address: mamolina@pangaeabiotech.com. 5. National Cancer Institute, 37 Convent Dr, 37/3060D, Bethesda, MD, United States. Electronic address: Ana_Robles@nih.gov. 6. Pathology Service, UGC Anatomía Patológica, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: eduardovillar6@gmail.com. 7. Medical Oncology Service, UGC Oncología Médica, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: juanramondelgado@gmail.com. 8. Department of Biochemistry, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, s/n, 18071 Granada, Spain. Electronic address: mfaus@ugr.es. 9. Department of Pharmacology, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, s/n, 18071 Granada, Spain. Electronic address: mangel.calleja.sspa@juntadeandalucia.es.
Abstract
BACKGROUND: Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients. METHODS: A prospective cohorts study was performed, including 170 NSCLC patients (114 Stage IIIB-IV, 56 Stage I-IIIA). IL1B (C > T; rs1143634), IL1B (C > T; rs12621220), IL1B (C > G; rs1143623), IL1B (A > G; rs16944), IL1B (C > T; rs1143627), IL6 (C > G; rs1800795), IL12A (C > T; rs662959), IL13 (A > C; rs1881457) and IL16 (G > T; rs7170924) gene polymorphisms were analyzed by PCR Real-Time. RESULTS: Patients with IL16 rs7170924-GG genotype were in higher risk of death (p = 0.0139; HR = 1.82; CI95% = 1.13-2.94) Furthermore, carriers of the TT genotype for IL12A rs662959 presented higher risk of progression in the non-resected NSCLC patient subgroup (p = 0.0412; HR = 4.49; CI95% = 1.06-18.99). The rest of polymorphisms showed no effect of on outcomes. CONCLUSIONS: Our results suggest that IL16 rs7170924-GG and IL12A rs662959-TT genotypes predict higher risk of death and progression, respectively, in NSCLC patients. No influence of IL1B rs12621220, IL1B rs1143623, IL1B rs16944, IL1B rs1143627, IL6 rs1800795, IL13 rs1881457 on NSCLC clinical outcomes was found in our patients.
BACKGROUND: Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLCpatients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLCpatients. METHODS: A prospective cohorts study was performed, including 170 NSCLCpatients (114 Stage IIIB-IV, 56 Stage I-IIIA). IL1B (C > T; rs1143634), IL1B (C > T; rs12621220), IL1B (C > G; rs1143623), IL1B (A > G; rs16944), IL1B (C > T; rs1143627), IL6 (C > G; rs1800795), IL12A (C > T; rs662959), IL13 (A > C; rs1881457) and IL16 (G > T; rs7170924) gene polymorphisms were analyzed by PCR Real-Time. RESULTS:Patients with IL16rs7170924-GG genotype were in higher risk of death (p = 0.0139; HR = 1.82; CI95% = 1.13-2.94) Furthermore, carriers of the TT genotype for IL12Ars662959 presented higher risk of progression in the non-resected NSCLCpatient subgroup (p = 0.0412; HR = 4.49; CI95% = 1.06-18.99). The rest of polymorphisms showed no effect of on outcomes. CONCLUSIONS: Our results suggest that IL16rs7170924-GG and IL12Ars662959-TT genotypes predict higher risk of death and progression, respectively, in NSCLCpatients. No influence of IL1Brs12621220, IL1Brs1143623, IL1Brs16944, IL1Brs1143627, IL6rs1800795, IL13rs1881457 on NSCLC clinical outcomes was found in our patients.