A NEIL1 single nucleotide polymorphism (rs4462560) predicts the risk of radiation-induced toxicities in esophageal cancer patients treated with definitive radiotherapy

Authors

  • Yun Chen MD,

    1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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    • The first 2 authors contributed equally to this article.

  • Meiling Zhu MD,

    1. Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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    • The first 2 authors contributed equally to this article.

  • Zhen Zhang MD,

    1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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  • Guoliang Jiang MD,

    1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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  • Xiaolong Fu MD,

    1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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  • Min Fan MD,

    1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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  • Menghong Sun MD,

    1. Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
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  • Qingyi Wei MD, PhD,

    Corresponding author
    1. Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
    2. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
    • Corresponding authors: Kuaile Zhao, MD, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, China; Fax: (011) 86-21-64174774; kuaile_z@sina.com; Qing-Yi Wei, MD, PhD, Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, China; Fax: (011) 86-21-64172585; weiqingyi@yahoo.com; or Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcomb Boulevard, Houston, TX 77401; Fax: (713) 563-0999; qwei@mdanderson.org

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  • Kuaile Zhao MD

    Corresponding author
    1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
    • Corresponding authors: Kuaile Zhao, MD, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, China; Fax: (011) 86-21-64174774; kuaile_z@sina.com; Qing-Yi Wei, MD, PhD, Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, China; Fax: (011) 86-21-64172585; weiqingyi@yahoo.com; or Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcomb Boulevard, Houston, TX 77401; Fax: (713) 563-0999; qwei@mdanderson.org

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Abstract

BACKGROUND

To assess the association between single nucleotide polymorphisms (SNPs) of base-excision repair genes and clinical outcomes, the roles of genetic variants of 3 selected genes—flap structure-specific endonuclease 1 (FEN1), 8-hydroxyguanine DNA glycosylase (hOGG1), and nei endonuclease VIII-like 1 (NEIL1)—were investigated in radiation-induced esophageal toxicity (RIET), radiation pneumonitis (RP), and overall survival (OS) after radio(chemo)therapy in patients with esophageal squamous cell carcinoma (ESCC).

METHODS

NEIL1 reference SNP 4462560 (rs4462560) and rs7402844, hOGG1 rs1052133 and rs293795, and FEN1 rs4246215 and rs174538 were genotyped in 187 patients with ESCC who received definitive radiotherapy with or without chemotherapy. Kaplan-Meier cumulative probabilities and Cox proportional hazards regression models were used to assess the effect of the genotypes on the risk of RIET, RP, and OS.

RESULTS

The authors observed that patients who had the NEIL1 rs4462560 GC/CC genotype had a statistically significantly lower risk of both grade ≥2 acute radiation-induced esophageal toxicity (RIET) (adjusted hazard ratio [HR], 0.421; 95% confidence interval [CI], 0.207-0.856; P = .017) and grade ≥2 acute radiation pneumonitis (RP) (adjusted HR, 0.392; 95% CI, 0.163-0.946; P = .037) compared with patients who had the GG genotype, but the genotype did not affect OS (adjusted HR, 0.778; 95% CI, 0.471-1.284; P = .326). There were no significant findings for other the SNPs under investigation.

CONCLUSIONS

The NEIL1 rs4462560 SNP may serve as a predictor of acute RIET and RP risk but not of OS. Larger prospective studies are needed to validate these findings. Cancer 2013;119:4205–4211. © 2013 American Cancer Society.

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