title: Correlation of DNA Repair Gene Polymorphisms With Clinical Outcome in Patients With Locally Advanced Non-Small-Cell Lung Cancer Receiving Induction Chemotherapy Followed by Surgery.
abstract: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery.
  
  
  
  A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival.
  
  
  
  The median survival was 32.14 months for carriers of XPD 312 Asp/Asp and 12.04 months for those with the variant Asn allele (P = .05). In addition, event-free survival was longer for patients with the XPD 312 Asp/Asp genotype compared with patients with Asp/Asn or Asn/Asn (P = .03). A similar but nonsignificant trend was observed for the XPD 751 genotype. In a multivariate analysis, complete resection and age emerged as prognostic factors for overall survival; in patients with incomplete resection or exploratory thoracotomy, XPD 312 was the most significant prognostic factor (P = .03).
  
  
  
  The XPD 312 single nucleotide polymorphism is a prognostic factor for survival in patients with locally advanced NSCLC receiving induction chemotherapy followed by surgery. The Asn allele is associated with unfavorable outcome and could be used for better stratification of patients.
authors.affiliation: Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy. Electronic address: c.santarpia@hotmail.com.
authors.forename: Mariacarmela
authors.initials: M
authors.lastname: Santarpia
authors.affiliation: Cancer Biology and Precision Medicine Program, Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Badalona, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ramirez
authors.affiliation: Cancer Biology and Precision Medicine Program, Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Badalona, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: de Aguirre
authors.affiliation: Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.affiliation: Cancer Biology and Precision Medicine Program, Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Badalona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pérez Cano
authors.affiliation: Cancer Biology and Precision Medicine Program, Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Queralt
authors.affiliation: Hospital San Carlos, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Gonzalez-Larriba
authors.affiliation: Hospital Clínico Universitario, Valencia, Spain.
authors.forename: Amelia
authors.initials: A
authors.lastname: Insa
authors.affiliation: Hospital Universitario Puerta de Hierro-Majadahonda (IDIPHIM), Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.affiliation: Hospital Clinico Lozano Blesa, Zaragoza, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Isla
authors.affiliation: Hospital General, Facultad Medicina, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
authors.affiliation: Consorcio Hospitalario de Terrassa, Terrassa, Spain.
authors.forename: Remei
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Medical Oncology Department, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Moran
authors.affiliation: Cancer Biology and Precision Medicine Program, Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Badalona, Spain; Dr Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona, Spain; Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012262:Ribonucleoside Diphosphate Reductase; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D043823:Taxoids; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D000077143:Docetaxel; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Locally advanced non-small cell lung cancer (NSCLC); Neoadjuvant chemotherapy; Ribonucleotide reductase subunit M1 (RRM1); Single nucleotide polymorphisms (SNPs); Xeroderma pigmentosum group D (XPD)