The first and second authors contributed equally to this work.
Genetic variants in one-carbon metabolism-related genes contribute to NSCLC prognosis in a Chinese population
Article first published online: 24 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 24, pages 5700–5709, 15 December 2010
How to Cite
Jin, G., Huang, J., Hu, Z., Dai, J., Tang, R., Chen, Y., Xu, L., Huang, X., Shu, Y. and Shen, H. (2010), Genetic variants in one-carbon metabolism-related genes contribute to NSCLC prognosis in a Chinese population. Cancer, 116: 5700–5709. doi: 10.1002/cncr.25301
- Issue published online: 3 DEC 2010
- Article first published online: 24 AUG 2010
- Manuscript Accepted: 9 FEB 2010
- Manuscript Revised: 8 FEB 2010
- Manuscript Received: 3 NOV 2009
- one-carbon metabolism;
One-carbon metabolism plays a critical role in DNA methylation and DNA synthesis. Variants of genes 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 this study, the authors hypothesized that polymorphisms in one-carbon metabolism-related genes may contribute to the prognosis of nonsmall cell lung cancer (NSCLC).
The authors 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. The Kaplan-Meier method with log-rank test and Cox proportional hazards model were used for survival analyses.
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 these four SNPs showed a locus-dosage effect on NSCLC survival (Ptrend = 6.9 × 10−5). In the final multivariate Cox regression model, combined genotypes based on 3 categories may be an independent prognostic factor for NSCLC with adjusted trend HR of 0.78 (95% CI, 0.66-0.92).
Genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis. Cancer 2010. © 2010 American Cancer Society.