The Association Of Single-nucleotide Polymorphism Rs13181 In ERCC2 With Risk And Prognosis Of Nasopharyngeal Carcinoma

Background:Nasopharyngeal carcinoma（NPC）is one of the most common malignant tumors in the head and neck,and it is more common in southern China.It has a high degree of malignancy and early lymph node metastasis.With the rapid development of modern medical imaging,chemotherapy and radiotherapy technology,the early diagnosis rate and local control rate of NPC have been greatly improved,but there are still 20-30%of patients,especially advanced patients with distant metastasis and or local recurrence.Therefore,it is very important to find markers that can effectively predict the risk of recurrence and death.Studies have shown that the Lys751Gln（rs13181）polymorphism in the gene of excision repair cross-complementary group 2（ERCC2）can lead to functional changes in ERCC2,and thus there is a tendency to affect the risk of NPC,but similar studies are rare.Purpose:In this study,the distribution of genotypes of the rs13181 SNP of ERCC2 in nasopharyngeal carcinoma patients and normal population to analyze whether it is related to NPC related to the risk of occurrence.At the same time,we followed up the eligible NPC patients to explore the correlation between rs13181 genotype nasopharyngeal carcinoma risk and its prognosis.Methods:he genotyping of SNP rs13181 in 476 NPC patients（NPC group）and 561 cancer-free healthy normal people（control group）in NPC endemic areas of China was performed,and the frequency of GG,GT and TT genotypes in the two groups was compared To assess the association between rs13181genotype and NPC risk.From 476 NPC patients,368 eligible patients were selected to obtain follow-up data after standard treatment to study the potential correlation between SNP and TFS and OS.Results:1.rs13181 single nucleotide polymorphism and NPC riskThe sex ratio,smoking history and EBV-VCA-Ig A status of the two groups were significantly different,but there was no significant difference in age.After controlling the gender,age,smoking history and EBV virus-Ig A status of NPC group and control group by Logistic Regression.After correction,the NPC risk of TT genotype and GT gene were found.NPC risk（OR 1.240,95%CI0.792-1.940）and GT+GG genotype NPC risk（OR 1.267,95%CI 0.817-1.965）are similar.The ERCC2rs13181SNP may not be related to the risk of NPC.2.rs13181 single nucleotide polymorphism and NPC prognosisTFS univariate analysis results showed that patients with GG or GT genotype of rs13181 had significantly shorter TFS than patients with TT genotype(P=2.22×10^-4).Men have significantly shorter TFS than women（p=0.037）,patients with T3-T4 have significantly shorter TFS than patients with T₁-T₂（p=0.004）,and patients with stage III+IV have significantly higher TFS than patients with stage I+II shorten（p=0.040）.TFS of N₂-N₃patients was significantly lower than that of N₀-N₁patients,but it was not statistically significant（p=0.051）.There was no significant correlation between TFS and age,smoking history,drinking history,chemotherapy or EBV-VCA-Ig A status.TFS multivariate factor analysis showed that gender,N stage,and clinical stage were not independent risk factors affecting TFS,but GG or GT genotype(HR 2.423,95%CI 1.499-3.917,p=3.05×10^-4)and T₃-T₄（HR 2.072,95%CI1.111-3.864,p=0.022）is an independent risk factor affecting TFS deterioration.OS univariate analysis results showed that the OS of patients with GT or GG genotypes in rs13181 was significantly lower than that of patients with TT genotype（p=0.010）.The OS of males was significantly lower than that of females（p=0.027）,and the OS of T3-T4 patients was significantly lower than that of T1-T2 patients（p=0.007）.Compared with TFS,a higher clinical stage（p=0.082）and EBV-VCA-Ig A positive（p=0.050）have a tendency to reduce the overall survival time OS,but there is no statistical significance.Patients with a history of smoking also had a tendency to decrease the OS,but it was also not statistically significant（p=0.057）.OS was not significantly correlated with age,drinking history,chemotherapy or N stage.OS multivariate factor analysis showed that T stage,gender,smoking history,clinical stage,and EBV-VCA-Ig A status were not independent risk factors affecting OS,GG or GT genotype genotype（HR 2.282,95%CI1.303-3.995,P=0.004）is an independent risk factor affecting OS deterioration.Conclusion:1.The ERCC2rs13181SNP of the nucleotide excision repair pathway may not be related to the risk of NPC;2.The ERCC2rs13181SNP of the nucleotide excision repair pathway and T stage are independent risk factors related to the risk of recurrence in NPC patients;3.The ERCC2rs13181SNP of the nucleotide excision repair pathway is an independent risk factor associated with the risk of death in NPC patients.