Potential Functional Variants in DNA Repair Genes Are Associated with Efficacy and Toxicity of Radiotherapy in Patients with Non-Small-Cell Lung Cancer

BACKGROUND: Lung cancer is one of the leading causes of cancer-related deaths. Radiotherapy, either alone or with chemotherapy, is still the primary treatment for patients with non-small-cell lung cancer (NSCLC). There are variations in how patients with NSCLC respond to radiotherapy and how toxic the therapy is. DNA repair gene polymorphisms are related to cancer development; however, their association with radiotherapy outcomes remains unknown. We hypothesized that gDNA repair gene variation could affect the efficacy and toxicity of radiotherapy in patients with NSCLC. METHODS: A total of 486 histologically confirmed patients with NSCLC were recruited from the Shengjing Hospital of China Medical University from July 2015 to September 2019. Eleven potentially functional single nucleotide polymorphisms (SNPs) in four DNA repair genes (XRCC1, XRCC2, XPD, and MSH2) were genotyped in these patients. A multiple factor logistic regression analysis was used to assess the association between these SNPs and the efficacy and toxicity of radiotherapy. RESULTS: Three SNPs, rs25487 (XRCC1), rs3218556 (XRCC2), and rs13181 (XPD), were all significantly associated with the efficacy of radiotherapy. The allele frequencies of the rs25487 CC genotype (OR = 0.457, 95% CI = 0.259–0.804, p=0.006) and the rs3218556 AG or AA genotypes (AG genotype: OR = 0.664, 95% CI = 0.442–0.999, p=0.049; AA genotype: OR = 0.380, 95% CI = 0.181–0.795, p=0.008) were both significantly higher in the response group than in the nonresponse group. For rs13181, the radiotherapy efficacy was associated with the heterozygous genotype GT (OR = 1.663, 95% CI = 1.057–2.614,p=0.027). Statistically significant associations between radiation-induced toxic reactions and rs25487 (XRCC1), rs3218556 (XRCC2), and rs13181 (XPD) were also observed. The rs13181GT genotype was associated with lower toxic reactions than the TT genotype (OR = 1.680, 95% CI = 1.035–2.728,p=0.035). CONCLUSIONS: The variants rs25487 (XRCC1), rs3218556 (XRCC2), and rs13181 (XPD) all contribute to the efficacy and toxicity of radiotherapy in patients with NSCLC. Our findings may clarify the predictive value of DNA repair genes for prognosis in patients with NSCLC after radiotherapy. Further investigation of more genes and samples should be performed to confirm our findings.