title: Genetic prediction of long-term survival after neoadjuvant chemoradiation in locally advanced esophageal cancer.
abstract: Candidate genes involved in DNA repair, 5-fluorouracil metabolism and drug detoxification were genotyped in 124 patients receiving neoadjuvant chemoradiation treatment for locally advanced esophageal cancer and their predictive role for long-term relapse-free survival (RFS) and cancer-specific survival (CSS) were evaluated. A panel including MTHFR 677TT, MDR1 2677GT, GSTP1 114CC, XPC 499CC and XPC 939AC+CC, defined as high-risk genotypes, discriminated subgroups with significantly different outcomes. When the panel was combined with histology, patients split into two subsets with 5-year RFS and CSS rates of 65% vs 27% (hazard ratio (HR) 3.0, P<0.0001) and 69% vs 31% (HR 2.9, P<0.0001), respectively. Combining the 5-single-nucleotide polymorphism (5-SNP) panel with pathological response defined two major informative risk classes with 5-year PFS and CSS rates of 79.4% vs 17.7% (HR 6.71, P<0.0001) and 79.3% vs 26.3% (HR 6.25, P<0.0001), respectively. This classification achieved a sensitivity of 79%, a specificity of 85.4% and an accuracy of 81.8%.
authors.affiliation: Department of Oncology, Laboratory of Pharmacology and Molecular Biology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gusella
authors.affiliation: Upper Gastrointestinal Surgery Division, University of Verona, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Giacopuzzi
authors.affiliation: Department of Oncology, Laboratory of Pharmacology and Molecular Biology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bertolaso
authors.affiliation: Upper Gastrointestinal Surgery Division, University of Verona, Verona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zanoni
authors.affiliation: Department of Oncology, Laboratory of Pharmacology and Molecular Biology, Azienda ULSS 18-Rovigo, Rovigo, Italy.|Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pezzolo
authors.affiliation: Department of Oncology, Unit of Medical Oncology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: Y
authors.initials: Y
authors.lastname: Modena
authors.affiliation: Department of Oncology, Unit of Medical Oncology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Menon
authors.affiliation: Department of Oncology, Laboratory of Pharmacology and Molecular Biology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Paganin
authors.affiliation: Upper Gastrointestinal Surgery Division, University of Verona, Verona, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Weindelmayer
authors.affiliation: Department of Oncology, Unit of Medical Oncology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Crepaldi
authors.affiliation: Upper Gastrointestinal Surgery Division, University of Verona, Verona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Manzoni
authors.affiliation: Department of Oncology, Unit of Medical Oncology, Azienda ULSS 18-Rovigo, Rovigo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pasini
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor