Goretti Duran1,2, Raquel Cruz3, Santiago Aguín4,5, Francisco Barros6, José María Giráldez7,8, Beatriz Bernárdez7,8, Irene Zarra7,8, Rafael López-López4,5, Ángel Carracedo9, María Jesús Lamas8. 1. Pharmacy Department, Clinical University Hospital of Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706, Santiago, Spain. goretti.duran.pineiro@sergas.es. 2. Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Trav. Choupana s/n, 15706, Santiago, Spain. goretti.duran.pineiro@sergas.es. 3. Center for Biomedical Research on Rare Diseases (CIBERER), Genomics Medicine Group, CIMUS, University of Santiago de Compostela, Avenida de Barcelona s/n, 15782, Santiago, Spain. raquel.cruz@usc.es. 4. Department of Medical Oncology, Clinical University Hospital of Santiago de Compostela (SERGAS), 15706, Santiago, Spain. 5. Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706, Santiago, Spain. 6. Genomic Medicine Group, CIBERER, Fundación Pública Galega de Medicina Xenómica-SERGAS, Trav. Choupana s/n, 15706, Santiago, Spain. 7. Pharmacy Department, Clinical University Hospital of Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706, Santiago, Spain. 8. Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Trav. Choupana s/n, 15706, Santiago, Spain. 9. Genomic Medicine Group, CIBERER, Fundación Pública Galega de Medicina Xenómica-SERGAS, Health Research Institute of Santiago (IDIS), University of Santiago de Compostela, Trav. Choupana s/n, 15706, Santiago, Spain. angel.carracedo@usc.es.
Abstract
PURPOSE: Genetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherapy (CRT). METHODS: These SNPs were genotyped in 110 patients using the iPLEX Gold assay on the MassARRAY method in blood DNA samples and used Kaplan-Meier and Cox regression analyses to compare genotype groups with the survival. RESULTS: Two SNPs, rs717620 (ABCC2) and rs12934241 (MMP2) were strongly associated with overall survival (OS) and disease-free survival (DFS). At a median follow-up of 64.4 months, the allele A of rs717620 (ABCC2) had an increased risk of disease progression {hazard ratio [HR] = 1.79, p = 0.0018} and death (HR = 2.0, p = 0.00027). ABCC2 was associated with OS after a Bonferroni adjustment for multiple testing. The MMP2 rs12934241-T allele was associated with an increased risk of worse OS and DFS (p = 0.0098 and p = 0.0015, respectively). One SNP of ABCB1 and three SNPs located in the ERCC2 gene showed an association with response in the subgroup of HNC patients treated with definitive CRT. CONCLUSIONS: Our findings highlight the potential usefulness of SNPs in different genes involved in drug metabolism and repair DNA to predict the response and survival to CRT. ABCC2 is a potential predictor of OS in patients with HNC.
PURPOSE: Genetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherapy (CRT). METHODS: These SNPs were genotyped in 110 patients using the iPLEX Gold assay on the MassARRAY method in blood DNA samples and used Kaplan-Meier and Cox regression analyses to compare genotype groups with the survival. RESULTS: Two SNPs, rs717620 (ABCC2) and rs12934241 (MMP2) were strongly associated with overall survival (OS) and disease-free survival (DFS). At a median follow-up of 64.4 months, the allele A of rs717620 (ABCC2) had an increased risk of disease progression {hazard ratio [HR] = 1.79, p = 0.0018} and death (HR = 2.0, p = 0.00027). ABCC2 was associated with OS after a Bonferroni adjustment for multiple testing. The MMP2 rs12934241-T allele was associated with an increased risk of worse OS and DFS (p = 0.0098 and p = 0.0015, respectively). One SNP of ABCB1 and three SNPs located in the ERCC2 gene showed an association with response in the subgroup of HNC patients treated with definitive CRT. CONCLUSIONS: Our findings highlight the potential usefulness of SNPs in different genes involved in drug metabolism and repair DNA to predict the response and survival to CRT. ABCC2 is a potential predictor of OS in patients with HNC.
Authors: Goretti Duran; Santiago Aguín; Raquel Cruz; Francisco Barros; José María Giráldez; Beatriz Bernárdez; Rafael López-López; Ángel Carracedo; María Jesús Lamas Journal: Head Neck Date: 2019-04-11 Impact factor: 3.147
Authors: Reginald V N Lord; Jan Brabender; David Gandara; Vicente Alberola; Carlos Camps; Manuel Domine; Felip Cardenal; José M Sánchez; Paul H Gumerlock; Miquel Tarón; José J Sánchez; Kathleen D Danenberg; Peter V Danenberg; Rafael Rosell Journal: Clin Cancer Res Date: 2002-07 Impact factor: 12.531