title: MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.
abstract: Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2-12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cecchin
authors.affiliation: Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Perrone
authors.affiliation: Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Nobili
authors.affiliation: Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico- National Cancer Institute, via Franco Gallini, Aviano, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: De Mattia
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Zanusso
authors.affiliation: Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Petreni
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto- IRCCS, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Medical Oncology Unit, University Hospital, Piazza S. Maria Della Misericordia, Udine, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Pella
authors.affiliation: Medical Oncology Unit, 'San Filippo Neri Hospital', Piazza Di S. Maria Della Pieta', Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Andrea
authors.affiliation: Medical Oncology Unit, Ospedale Civile di Vittorio Veneto, Vittorio, Veneto (TV), Italy.
authors.forename: D
authors.initials: D
authors.lastname: Errante
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rizzolio
authors.affiliation: Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Mazzei
authors.affiliation: Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Landini
authors.affiliation: Section of Internal Medicine , Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D011743:Pyrimidines; D000077150:Oxaliplatin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C030986:pyrimidine