Potentially functional variants of autophagy-related genes are associated with the efficacy and toxicity of radiotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND:Nasopharyngeal carcinoma (NPC) is one of the major invasive malignant neoplasms of head and neck, while radiotherapy is the primary therapy for NPC. Genetic variants could affect the efficacy and toxicities of radiotherapy in NPC patients. METHODS:In the current study, we aimed to investigate 10 potentially functional SNPs of autophagy-related genes (ATG) with the efficacy and toxicity of radiotherapy in 468 NPC patients. RESULTS:We found ATG10 rs10514231, rs1864183, and rs4703533 were significantly associated with worse efficacy of radiotherapy at both at the primary tumor and lymph node, while ATG16L2 rs10898880 was significantly associated with better efficacy of radiotherapy at both primary tumor and lymph node. Besides, we also found ATG10 rs10514231 and ATG16L2 rs10898880 were significantly associated with the occurrence of grade 3-4 oral mucositis (allelic model, for rs10514231: OR = 1.95, 95% CIs = 1.31-2.9, p = .001; for rs10898880: OR = 1.56, 95% CIs = 1.19-2.04, p = .001) and grade 3-4 myelosuppression (allelic model, for rs10514231: OR = 2.08, 95% CIs = 1.39-3.09, p < .001; for rs10898880: OR = 1.51, 95% CIs = 1.1-2.06, p = .010). CONCLUSIONS:This should be the first report identifying ATG10 rs10514231, rs1864183, rs4703533, and ATG16L2 rs10898880 could contribute to the efficacy and toxicity of radiotherapy in NPC patients. Further investigation of the underlying molecular mechanisms and prospective clinical trials in NPC patients are needed to validate our results.

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