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Qinghuan Li,1,* Yi Liang,1,* Zeng Liu,2 Chuanyun Yu1 1Oncology Radiotherapy Center, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China; 2Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanyun Yu Tel/Fax +86-710-2813559Email yuchuanyunxy@163.comZeng Liu Email liu8901@126.comBackground: Head and neck squamous cell carcinoma (HNSCC) ranks the sixth most common cancer worldwide. This study aims to evaluate the associations of GWAS-identified HNSCC risk loci with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy.Methods: Six GWAS-identified risk loci were genotyped and evaluated. Multivariate logistic regression was used to determine the associations of these SNPs with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy.Results: We found that rs259919 was significantly associated with higher TNM stage (allele A vs G: OR=1.49; 95% CI: 1.09– 2.03; P=0.012), while rs3135001 was significantly associated with better efficacy of radiotherapy (allele T vs C: OR=1.80, 95% CIs=1.19– 2.73, P=0.005). Both SNP rs1265081 (allele A vs C: OR=1.41, 95% CIs=1.08– 1.86, P=0.012) and rs3135001 (allele T vs allele C: OR=0.53, 95% CIs=0.35– 0.79, P=0.002) were significantly associated with the occurrence of grade 3– 4 oral mucositis.Conclusion: We identified that three GWAS-identified HNSCC risk loci were significantly associated with progression, efficacy and toxicity of radiotherapy of HNSCC. Our findings strengthen the understanding of the essential role of genetic background in the progression and therapeutic effects of HNSCC.Keywords: progression, genetic, radiotherapy, HNSCC, efficacy, toxicity

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