Effect of the methylenetetrahydrofolate reductase C677T polymorphism on patients with cisplatin/gemcitabine-treated stage IV non-small-cell lung cancer.
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.
Alberola
Vicente
V
Medical Oncology Service, Hospital Arnau de Vilanova, Valencia, Spain.
Sarries
Carme
C
Rosell
Rafael
R
Taron
Miquel
M
de las Peñas
Ramon
R
Camps
Carlos
C
Massuti
Bartomeu
B
Insa
Amelia
A
Garcia-Gomez
Ramon
R
Isla
Dolores
D
Artal
Angel
A
Muñoz
Miguel Angel
MA
Cobo
Manuel
M
Bover
Isabel
I
Gonzalez-Larria
Jose Luis
JL
Terrasa
Josefa
J
Almenar
Daniel
D
Barcelo
Ramon
R
Diz
Pilar
P
Sanchez-Ronco
Maria
M
Sanchez
Jose Javier
JJ
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
D014408:Biomarkers, Tumor; D006710:Homocysteine; D003841:Deoxycytidine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002945:Cisplatin; D000093542:Gemcitabine