Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C>T polymorphism in non-small cell lung carcinoma.
BACKGROUND
Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC.


METHODS
Fifty patients among a cohort of 763 with NSCLC were selected based on CT gene expression status and typed for five polymorphisms in four genes known to affect SAM generation by allele specific q-PCR and RFLP.


RESULTS
We identified a significant association between CT gene expression and the MTHFR 677 CC genotype, as well as the C allele of the SNP, in this cohort of patients. Multivariate analysis revealed that the genotype and allele strongly associate with CT gene expression, independent of potential confounders.


CONCLUSIONS
Although CT gene expression is associated with DNA demethylation, in NSCLC, our data suggests this is unlikely to be the result of decreased MTHFR function.
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey. agure@bilkent.edu.tr.
Kerem M
KM
Senses
Mithat
M
Gonen
Ahmet R
AR
Barutcu
Zeynep
Z
Kalaylioglu
Murat
M
Isbilen
Ozlen
O
Konu
Yao T
YT
Chen
Nasser K
NK
Altorki
Ali O
AO
Gure
D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D013737:Testis / Q000378:metabolism*
D042965:Methylenetetrahydrofolate Reductase (NADPH2)