Genetic variants in one-carbon metabolism-related genes contribute to NSCLC prognosis in a Chinese population.
BACKGROUND
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).


METHODS
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.


RESULTS
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 (P(trend) = 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).


CONCLUSIONS
Genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis.
Jin
Guangfu
G
Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.
Huang
Jinlin
J
Hu
Zhibin
Z
Dai
Juncheng
J
Tang
Rong
R
Chen
Yijiang
Y
Xu
Lin
L
Huang
Xinen
X
Shu
Yongqian
Y
Shen
Hongbing
H
D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D019175:DNA Methylation; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D015778:Minor Histocompatibility Antigens; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D013762:Tetrahydrofolate Dehydrogenase; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)