RGD Reference Report - Prognostic significance of folate metabolism polymorphisms for lung cancer. - Rat Genome Database

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Prognostic significance of folate metabolism polymorphisms for lung cancer.

Authors: Matakidou, A  El Galta, R  Rudd, MF  Webb, EL  Bridle, H  Eisen, T  Houlston, RS 
Citation: Matakidou A, etal., Br J Cancer. 2007 Jul 16;97(2):247-52. Epub 2007 May 29.
RGD ID: 4891158
Pubmed: PMID:17533396   (View Abstract at PubMed)
PMCID: PMC2360297   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.bjc.6603830   (Journal Full-text)

Functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) of folate metabolism genes can influence the methylation of tumour suppressor genes, thereby potentially impacting on tumour behaviour. To investigate whether such polymorphisms influence lung cancer survival, we genotyped 14 nsSNPs mapping to methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2), methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non-small cell (NSCLC) and 154 with small cell lung cancer (SCLC). The most significant association detected was with MTHFS Thr202Ala, with carriers of variant alleles having a worse prognosis (hazard ratio (HR)=1.49; 95% confidence interval: 1.14-1.94). Associations were also detected between overall survival (OS) in SCLC and homozygosity for MTHFR 222Val (HR=1.92; 1.03-3.58) and between OS from NSCLC and MTRR 175Leu carrier status (HR=1.36; 1.06-1.75). While there is evidence that variation in the folate metabolism genes may influence prognosis from lung cancer, current data are insufficiently robust to distinguish individual patient outcome.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung small cell carcinoma severityIAGP 4891158protein:missense mutation:cds:p.A222V (human)RGD 
lung small cell carcinoma severityISOMTHFR (Homo sapiens)4891158; 4891158protein:missense mutation:cds:p.A222V (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mthfr  (methylenetetrahydrofolate reductase)

Genes (Mus musculus)
Mthfr  (methylenetetrahydrofolate reductase)

Genes (Homo sapiens)
MTHFR  (methylenetetrahydrofolate reductase)


Additional Information