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

Authors

  • Guangfu Jin MD, PhD,

    1. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China
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    • The first and second authors contributed equally to this work.

  • Jinlin Huang PhD,

    1. Berkeley Biotech Inc, Taizhou, Jiangsu, China
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    • The first and second authors contributed equally to this work.

  • Zhibin Hu MD, PhD,

    1. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China
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  • Juncheng Dai MD,

    1. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China
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  • Rong Tang PhD,

    1. Berkeley Biotech Inc, Taizhou, Jiangsu, China
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  • Yijiang Chen MD,

    1. Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Lin Xu MD,

    1. Department of Thoracic Surgery, Jiangsu Cancer Hospital, Nanjing, China
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  • Xinen Huang MD, PhD,

    1. Department of Oncology, Jiangsu Cancer Hospital, Nanjing, China
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  • Yongqian Shu MD,

    Corresponding author
    1. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China
    2. Department of Oncology, Jiangsu Key Discipline of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    • Department of Oncology, Jiangsu Key Discipline of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
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  • Hongbing Shen MD, PhD

    Corresponding author
    1. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China
    2. Department of Oncology, Jiangsu Key Discipline of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    • Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, China
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    • Fax: (011) 86-25-8652-7613


Abstract

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 (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).

CONCLUSION:

Genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis. Cancer 2010. © 2010 American Cancer Society.

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