title: Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.
abstract: Genetic variants in DNA repair genes may play a role in the effectiveness of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17 SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2) involved in DNA repair mechanisms and its association with outcome in NSCLC. This prospective study included patients with stages III and IV treated with platinum-based chemotherapy. All patients (n = 161) received cisplatin or carboplatin plus a third-generation drug. Additionally, stage IIIA and IIIB patients (n = 74) received concomitant or sequential radiotherapy. Germline polymorphisms were analyzed using the BioMark system in blood DNA samples. We found that in stage III patients, response was significantly associated with SNPs in ERCC1 and in ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the ERCC2 gene. In stage IV patients, response was associated with a genetic variant in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of the DNA repair mechanisms along with the heterogeneity in the treatment of lung cancer could explain the role of multiple genes as putative biomarkers of patient outcome.
authors: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau., Sant Antoni Maria Claret 167, 08025 Barcelona, Spain; Universitat Autònoma de Barcelona (UAB), Spain.
authors: Ivana
authors: I
authors: Sullivan
authors: Genetics Departments, Hospital de la Santa Creu i Sant Pau., Spain; U-705 CIBERER, Barcelona, Spain.
authors: Juliana
authors: J
authors: Salazar
authors: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau., Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors: Margarita
authors: M
authors: Majem
authors: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau., Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors: Cinta
authors: C
authors: Pallarés
authors: Genetics Departments, Hospital de la Santa Creu i Sant Pau., Spain; U-705 CIBERER, Barcelona, Spain.
authors: Elisabeth
authors: E
authors: Del Río
authors: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau., Sant Antoni Maria Claret 167, 08025 Barcelona, Spain. Electronic address: dpaez@santpau.cat.
authors: David
authors: D
authors: Páez
authors: Genetics Departments, Hospital de la Santa Creu i Sant Pau., Spain; U-705 CIBERER, Barcelona, Spain.
authors: Montserrat
authors: M
authors: Baiget
authors: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau., Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors: Agustí
authors: A
authors: Barnadas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; C072022:XPBC-ERCC-3 protein; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin
keywords: DNA repair; Non-small cell lung cancer; Platinum-based chemotherapy; Radiotherapy; Single nucleotide polymorphisms