title: Effect of the methylenetetrahydrofolate reductase C677T polymorphism on patients with cisplatin/gemcitabine-treated stage IV non-small-cell lung cancer.
abstract: Single nucleotide polymorphisms (SNPs) in the metabolic pathways of S-adenosylmethionine have been related to global hypomethylation and a lower number of hypermethylated CpG islands of tumor suppressor genes. Hypermethylation of checkpoint and DNA repair genes has been shown to be indicative of chemosensitivity. In the present study, we have examined the SNP of methylenetetrahydrofolate reductase (MTHFR) C677T, which affects DNA methylation patterns and is linked to elevated plasma homocysteine levels in 208 patients with gemcitabine/cisplatin-treated stage IV non-small-cell lung cancer (NSCLC). No differences in response rate were observed according to the MTHFR genotype. However, time to progression was 7.4 months for 68 patients with CC genotype, 5.5 months for 108 patients with heterozygous CT genotype, and 5.2 months for 28 patients with TT genotype. These findings can lead us to distinguish different outcome patterns among patients with stage IV NSCLC whose similar clinical prognostic factors would otherwise indicate similar outcomes. Carriers of the MTHFR 677T allele could benefit from supplementation with folic acid and vitamin B12. The Spanish Lung Cancer Group has undertaken a phase III randomized trial to elucidate this concept.
authors.affiliation: Medical Oncology Service, Hospital Arnau de Vilanova, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Alberola
authors.forename: Carme
authors.initials: C
authors.lastname: Sarries
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Ramon
authors.initials: R
authors.lastname: de las Peñas
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Amelia
authors.initials: A
authors.lastname: Insa
authors.forename: Ramon
authors.initials: R
authors.lastname: Garcia-Gomez
authors.forename: Dolores
authors.initials: D
authors.lastname: Isla
authors.forename: Angel
authors.initials: A
authors.lastname: Artal
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Muñoz
authors.forename: Manuel
authors.initials: M
authors.lastname: Cobo
authors.forename: Isabel
authors.initials: I
authors.lastname: Bover
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Gonzalez-Larria
authors.forename: Josefa
authors.initials: J
authors.lastname: Terrasa
authors.forename: Daniel
authors.initials: D
authors.lastname: Almenar
authors.forename: Ramon
authors.initials: R
authors.lastname: Barcelo
authors.forename: Pilar
authors.initials: P
authors.lastname: Diz
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Ronco
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Sanchez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D019175:DNA Methylation; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D006710:Homocysteine; D003841:Deoxycytidine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002945:Cisplatin; D000093542:Gemcitabine