Abstract
Abstract One-carbon metabolism plays a critical role in both DNA methylation and DNA synthesis. Genetic variants of genes coding enzymes involved in one-carbon metabolism may result in aberrant methylation and/or DNA synthesis inhibition, and ultimately modulate the initiation and progression of tumors. In the present study, we hypothesized that polymorphisms in one-carbon metabolism related genes may contribute to the prognosis of non-small cell lung cancer (NSCLC). To test this hypothesis, we screened 57 potentially functional single nucleotide polymorphisms (SNPs) from 11 candidate genes involved in one-carbon metabolism and genotyped them in a cohort of 568 NSCLC patients by using Illumina Golden Gate platform. Kaplan-Meier method with log-rank test and Cox proportional hazard models were used for the survival analyses. We found that variant alleles were significantly associated with favorable survivals of NSCLC for MTR rs3768160 A>G (allelic hazards ratio (HR) = 0.78, 95% confidence interval (CI): 0.62-0.98), MTRR rs2966952 G>A (allelic HR = 0.84, 95%CI: 0.71-0.99) and DHFR rs1650697 G>A (allelic HR = 0.83, 95%CI: 0.70-0.99), and with unfavorable prognosis for MTHFD1 rs1950902 G>A with borderline significance (allelic HR = 1.18, 95%CI: 0.99-1.40). In addition, the combined genotypes of above four SNPs showed a locus-dosage effect on NSCLC survival (P for trend = 6.9 × 10−5). In the final multivariate Cox regression model, combined genotypes were identified as an independent prognostic factor for NSCLC with adjusted HR of 0.78 (95% CI: 0.66-0.92; P = 3.7 × 10−3). These findings indicate that genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 908.
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