DNA 修复基因 NEIL1 中的遗传变异与肺癌患者放射性肺炎风险相关。
Genetic variations in DNA repair gene NEIL1 associated with radiation pneumonitis risk in lung cancer patients.
机构信息
Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Radiation Oncology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Mol Genet Genomic Med. 2021 Jul;9(7):e1698. doi: 10.1002/mgg3.1698. Epub 2021 Jun 9.
BACKGROUND
Radiation pneumonitis (RP) is a common side effect in lung cancer patients who received radiotherapy. Our previous study found genetic variations in DNA repair gene NEIL1 may be a predictor of RP in patients with esophageal cancer. So, we hypothesis genetic variations in NEIL1 gene could affect the risk of RP in lung cancer patients following radiotherapy.
METHODS
Genetic variations rs4462560 G>C and rs7402844 C>G in NEIL1 gene were genotyped in 174 lung cancer patients received radio(chemo)therapy. Luciferase assay, real-time PCR and Western blot were used to access the effect of the variants on NEIL1 in HELF and HEF cell lines which were transfected with plasmids containing rs4462560 G>C and rs7402844 C>G.
RESULTS
Patients with rs4462560 CC genotype had a lower risk of RP grade ≥2 than GG genotype. Compared with the CC genotype, rs7402844 GG genotype was associated with an increased RP grade ≥2 risk. What is more, rs4462560 G decreased the relative luciferase activity of NEIL1 gene promoter compared with the negative control in vitro, while rs4462560 C can increase the relative luciferase activity. The mRNA and protein level of the NEIL1 gene in rs4462560 G were lower than rs4462560 C.
CONCLUSIONS
Genetic variants of NEIL1 are associated with RP risk through regulation of NEIL1 expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.
背景
放射性肺炎（RP）是接受放疗的肺癌患者的常见副作用。我们之前的研究发现，DNA 修复基因 NEIL1 的遗传变异可能是食管癌患者 RP 的预测因子。因此，我们假设 NEIL1 基因的遗传变异可能会影响接受放疗的肺癌患者发生 RP 的风险。
方法
在 174 例接受放（化）疗的肺癌患者中，对 NEIL1 基因中的 rs4462560 G>C 和 rs7402844 C>G 遗传变异进行了基因分型。荧光素酶检测、实时 PCR 和 Western blot 用于评估转染含有 rs4462560 G>C 和 rs7402844 C>G 质粒的 HELF 和 HEF 细胞系中变体对 NEIL1 的影响。
结果
与 GG 基因型相比，rs4462560 CC 基因型的患者发生 RP 分级≥2 的风险较低。与 CC 基因型相比，rs7402844 GG 基因型与 RP 分级≥2 的风险增加相关。此外，与阴性对照相比，rs4462560 G 降低了 NEIL1 基因启动子的相对荧光素酶活性，而 rs4462560 C 可以增加相对荧光素酶活性。rs4462560 G 的 NEIL1 基因 mRNA 和蛋白水平低于 rs4462560 C。
结论
NEIL1 的遗传变异通过调节 NEIL1 表达与 RP 风险相关，并可作为预测接受胸部放疗的患者发生 RP 的独立生物标志物。
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