title: EGFR ligands and DNA repair genes: genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer.
abstract: Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sebio
authors.affiliation: 1] Department of Genetics, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain [2] U-705 CIBERER, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Páez
authors.affiliation: IDIBELL-Institut Català d'Oncologia, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Berenguer-Llergo
authors.affiliation: Department of Genetics, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Del Río
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Tobeña
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martín-Richard
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Sullivan
authors.affiliation: Department of Surgery, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Targarona
authors.affiliation: Department of Radiotherapy, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Balart
authors.affiliation: 1] Department of Genetics, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain [2] U-705 CIBERER, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Baiget
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Ceu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Barnadas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000379:methods*; D015331:Cohort Studies; D004260:DNA Repair / Q000235:genetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008024:Ligands; D003841:Deoxycytidine; D000069287:Capecitabine; C512478:EGFR protein, human; D066246:ErbB Receptors; D005472:Fluorouracil