title: Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab.
abstract: Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1, and XRCC5). The results were then correlated with time to progression (TTP), overall survival (OS), and toxicity (epithelitis, mucositis, and folliculitis). The median TTP and OS were better in patients with severe vs mild mucositis (17 vs 7 months, p = 0.03; and 26 vs 12 months, p = 0.016, respectively) and folliculitis (10 vs 7 months, p = 0.01, and 26 vs 10 months, p < 0.001, respectively). Patients with the HIF-1α CT/TT genotype had better OS than those with the wild-type HIF-1α CC genotype (28 vs 13 months, p = 0.035). Patients with the XRCC5 GG/AA genotype had longer TTP than patients with the XRCC5 AG genotype (11 vs 7 months, p = 0.035). Severe skin toxicity and SNPs of HIF-1α and XRCC5 were associated with different outcomes among patients treated with radiotherapy plus cetuximab.
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, Medical School, University of Barcelona, Barcelona, Spain. carmen.munoz@ub.edu.|Otolaryngology-Head and Neck Department-IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. carmen.munoz@ub.edu.|Medical Oncology Department, Hospital Clinic, University of Barcelona, c/Villarroel, 170-08036, Barcelona, Spain. carmen.munoz@ub.edu.
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Otolaryngology-Head and Neck Department-IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. mcaba@clinic.ub.es.|Pathology Department, Hospital Clinic, Barcelona, Spain. mcaba@clinic.ub.es.|Medical Oncology Department, Hospital Clinic, University of Barcelona, c/Villarroel, 170-08036, Barcelona, Spain. mcaba@clinic.ub.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Caballero
authors.affiliation: Otolaryngology-Head and Neck Department-IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Radiation Oncology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: Sofia
authors.initials: S
authors.lastname: Hakim
authors.affiliation: Otolaryngology-Head and Neck Department-IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Medical Oncology Department, Hospital Clinic, University of Barcelona, c/Villarroel, 170-08036, Barcelona, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Verger
authors.affiliation: Otolaryngology-Head and Neck Department-IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Medical Oncology Department, Hospital Clinic, University of Barcelona, c/Villarroel, 170-08036, Barcelona, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Grau
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000068818:Cetuximab / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005499:Folliculitis / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D000072200:Ku Autoantigen / Q000235:genetics; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D052016:Mucositis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics; D016896:Treatment Outcome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000970:Antineoplastic Agents; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D000068818:Cetuximab; D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000072200:Ku Autoantigen; D006899:Mixed Function Oxygenases; D012097:Repressor Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000076105:X-ray Repair Cross Complementing Protein 1; D000099162:Endothelial PAS Domain-Containing Protein 1; C497396:ARNT protein, human; C000619371:XRCC1 protein, human; C439790:HIF1AN protein, human; C106893:XRCC5 protein, human
keywords: Cetuximab; Head and neck squamous cell carcinoma; Radiotherapy; Single-nucleotide polymorphism; Toxicity