Cancer-testis gene expression as a biomarker of the genetic variation in the one carbon metabolic pathway

Abstract

S-adenosyl methionine (SAM) is the sole methyl donor for all biological reactions in humans. Folate consumption, required for SAM generation, is also essential for dTMP synthesis and both events occur via enzymes of the one-carbon pathway. Frequently occurring alleles of these enzymes have occasionally been associated with several diseases including cancer. However, the cumulative effects of the polymorphic variants of these enzymes on S-adenosylmethionine production have not been studied. The identification of a biomarker that can reflect the collective effect of these allelic variants is critical in moving the field forwards. We hypothesized that Cancer-Testis (CT) genes, whose expression strongly correlates with DNA hypomethylation, could be such a biomarker. In this study, we have pursued an extensive correlation of CT expression and allelic variants of the several one-carbon pathway enzyme genes , including methyltetrahydrofolatereductase (MTHFR), methionine synthase (MS), reduced folate carrier (RFC) and methionine synthase reductase (MTRR) in non-small cell lung cancer. Our results revealed linkage disequilibrium among alleles as well as correlations between given genootypes and CT gene expression, and illuminate the critical next steps that need to be pursued.