| Objective:Studies have shown that genetic polymorphisms may be one of the main factors that affect individual differences on radiotherapy in patients with nasopharyngeal carcinoma(NPC).DSB DNA damage/repair pathway is the main way in the repair of radiation-induced injury,but presently it was failed to find any systematic report about the effect of single nucleotide polymorphism(SNP)in DSB DNA damage/repair pathway on radiotherapy.Thus we intend to clarify the impact of genetic polymorphisms in DSB DNA damage/repair pathway on radiotherapy in patients with NPC.Methods:1.Samples selection: 182 cases of untreated NPC patients were recruited into our research according to the inclusion and exclusion criteria.2.Evaluation methods: Acute radiation toxicity was scored using RTOG/EORTC grading system.The efficacy at the end of radiotherapy and 3 months after radiotherapy were evaluated by response evaluation criteria in solid tumors(RECIST).3.Analysis of genetic polymorphisms: According to the candidate gene approach,a total of 15 SNPs in 8 DSB DNA repair genes(XRCC3,XRCC4,XRCC5,XRCC6,ATM,ATR,Rec QL and NBN)were genotyped.Sequenom Mass Array method was used for SNPs analysis.4.Statistical analysis: T test,Chi-square test and Logistic regression were employed to assess the univariate and multivariate analysis.Results:1.The impact of genetic polymorphisms on acute radiation toxicity(1)Radiation mucositis: XRCC3 rs1799796 and ATM rs664143 had significant differences between G0-2 and G3+ radiation mucositis.Compared with AA genotype,patients with XRCC3 rs1799796 AG,GG and AG+GG had a significant lower risk of G3+ radiation mucositis(OR=0.446,95%CI=0.230-0.863,P=0.016;OR=0.148,95%CI=0.053-0.412,P=0.000 and OR=0.343,95%CI=0.184-0.640,P=0.001).Compared with AA+AG,patients with XRCC3 rs1799796 GG genotype also had a significant lower risk of G3+ radiation mucositis(OR=0.228,95%CI=0.088-0.592,P=0.002).The risk of G3+ radiation mucositis was lower in patients with ATM rs664143 AG and AG+GG genotypes than AA genotype(OR=0.509,95%CI=0.271-0.957,P=0.036;OR=0.550,95%CI=0.301-1.004,P=0.051).(2)Radiation dermatitis: NBN rs1805794 could significantly affect the development of G2+ radiation dermatitis.Patients with CC genotype had a higher risk of G2+ radiation dermatitis than GG and GG+GC genotypes(OR=3.284,95%CI=1.318-8.182,P=0.011;OR=2.637,95%CI= 1.217-5.710,P=0.014).2.The impact of genetic polymorphisms on radiation efficacy(1)The efficacy at the end of radiotherapy: ATM rs664143,NBN rs1805794 and Rec QL rs13035 had a significant impact on primary tumor efficacy at the end of radiotherapy.The likelihood of non-CR was higher in carriers of ATM rs664143 GG genotypes than AA and AA+AG genotypes(OR=3.634,95%CI=1.146-11.526,P=0.028;OR=3.044,95%CI= 1.073-8.633,P=0.036).Patients with NBN rs1805794 GC and GC+CC genotypes had a higher risk of non-CR than GG genotype(OR=2.704,95%CI= 1.094-6.682,P=0.031;OR=2.114,95%CI= 0.892-5.014,P=0.089).Patients with Rec QL rs13035 AC had a lower risk of non-CR than AA(OR=0.446,95%CI=0.209-0.956,P=0.038).The relationship between SNPs and the efficacy of lymph node at the end of radiotherapy was not found.(2)The efficacy 3 months after radiotherapy: XRCC3 rs1799796 could significantly affect the primary tumor efficacy(P=0.033 for AA:AG:GG).XRCC4 rs1805377(P=0.012 and 0.011 for AA:AG:GG and AA:(AG+GG)),Rec QL rs4987216(P=0.046 for GG:GA)and NBN rs1805794(P=0.004 for GG:GC:CC)were found to have significant relationship with the efficacy of lymph node.Conclusion:1.XRCC3 rs1799796 and ATM rs664143 may be the predictive factors for radiation mucositis and NBN rs1805794 may be the predictive factor for radiation dermatitis.2.ATM rs664143,NBN rs1805794 and Rec QL rs13035 may be used to predict the primary tumor efficacy at the end of radiotherapy.3.XRCC3 rs1799796 may be used to predict primary tumor efficacy 3 months after radiotherapy.XRCC4 rs1805377,Rec QL rs4987216 and NBN rs1805794 may be used to predict the efficacy of lymph node. |
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