The Relevant Research Between Single Nucleotide Polymorphisms Of XRCC1 Codon399 And Radiation Reaction Of Normal Tissue In Patients Of Nasopharyngeal Carcinoma

Objective: By detecting the single nucleotide polymorphisms of XRCC1 Codon399 of peripheral blood of patients suffering from nasopharyngeal carcinoma(NPC) ,to analyse the relation between single nucleotide polymorphisms of XRCC1 Codon399 and radiation injury in normal tissues.Methods:Phlebotomize 60 cases of patients with nasopharyngeal carcinoma which are all confirmed of low differentiated squamous cell carcinoma by pathology . Extract genome DNA from whole blood cells before radiotherapy. Then perform PCR, and amplify the PCR products by ligase detection reaction, put the LDR products on sequencer to carry out electrophoresis, get the genotype of XRCC1 Codon399, to observe the acute irradiation-induced injury of normal tissue during radiotherapy. To evaluate the clinical effects -in the mid-course,the last phase and three months after radiotherapy, to compare the acute and chronic radiation reactions of normal tissue in the different genotypes.Results:(1) Of all 60 cases, the number of XRCC1 Codon399 Gln/Gln was 6, accounting for 10%. Arg/Gln was 21, accounting for 35%. Arg/Arg was 33, accounting for 55%.There was no significant difference among the three genotypes on age, gender, clinical stage, T stage, N stage (P>0.05).(2) In mid-course of radiotherapy the regression rate of nasopharyngeal cancer with Gln/Gln genotype wa(s0.899±0.0590), obviously higer than Arg/Gln (0.488±0.0175) and Arg/Arg genotype(0.416±0.0189), There were significant differences among the three genotypes (P <0.05).(3) At the end of radiotherapy the regression rate of Gln/Gln genotype was (0.998±0.0020),obviously higer than that of Arg/Gln (0.817±0.0231) and Arg/Arg genotype(0.794±0.0159), there were significant differences among the three genotypes(P <0.05).(4) Three months after radiotherapy, the efficiency of cases (CR + PR) with Gln/Gln was 100%, Arg/Gln was 100%, Arg/Arg was 93.9%. But there was no significant difference among the three genotypes (P>0.05).(5) The relation between clinical stage and the efficiency in three months after radiotherapy. The efficiency of cases (CR + PR) was 100%, 96.2%, 85.7% at clinical stageⅠ,Ⅱ,Ⅲ,ⅣA respectively. The efficiency of Clinical stageⅠ,Ⅱ,Ⅲis higher than clinical stageⅣA. There were highly significant differences (P <0.01). But there was no significant difference among the clinical stageⅠ,Ⅱ,Ⅲ(P>0.05).(6) The relation between single nucleotide polymorphisms of XRCC1 Codon399 and acute radiation injury in normal tissues (skin, mucosa, parotid gland):All cases had suffered from the acute irradiation-induced injury in normal tissues to some extent. The rate of the acute irradiation-induced injury of skin at Grade 1 ,2, 3 was all 33.3% with Gln/Gln genotype,52.3%, 42.9%, 4.8% with Arg / Gln and 57.6%, 36.3%, 6.1% with Arg / Arg genotype respectively. The rate of the acute irradiation-induced injury of mucosa at Grade 1 ,2, 3 was 33.3%, 50.0%, 16.7% with Gln/Gln, 38.1%, 52.4%, 9.5% with Arg/Gln and 48.5% , 42.4%, 9.1% with Arg/Arg genotype respectively. The rate of the acute irradiation-induced injury of parotid gland at Grade 1 ,2 was 0%, 100% with Gln/Gln, 33.3%, 66.7% with Arg/Gln, 36.4%, 63.6% with Arg/Arg genotype, respectively. All results showed there was no significant difference among the three genotypes (P>0.05). (7) The relation between single nucleotide polymorphisms of XRCC1 Codon399 and chronic radiation injury in normal tissues (skin, subcutaneous tissue, mucosa, parotid gland):All cases had suffered from the chronic irradiation-induced injury in normal tissues to some extent. The rate of the chronic irradiation-induced injury of skin at Grade 1 ,2, 3 was 33.3%, 66.7%%, 0% with Gln/Gln, 52.4%,42.9%,4.7% with Arg/Gln, 63.6%,36.4%, 0% with Arg/Arg genotype respectively. The rate of the chronic irradiation-induced injury of subcutaneous tissue at Grade 1 ,2, 3 was 33.3%, 66.7%%, 0% with Gln/Gln 42.4%, 57.6%, 0% with Arg/Gln , 38.1%,57.2%,4.7% with Arg/Arg genotype .The rate of the chronic irradiation-induced injury of mucosa at Grade 1, 2, 3 was 100%, 0%, 0% with Gln/Gln, 93.9%, 6.1%, 0% with Arg / Gln, 80.9%, 14.3%, 4.7% with Arg/Arg genotype respectively. The rate of the chronic irradiation-induced injury of parotid gland at Grade 1 ,2, 3 was 100%, 0%, 0% with Gln/Gln, 93.9%, 6.1%, 0% with Arg/Gln , 80.9%, 14.3%, 4.7% with Arg/Arg genotype respectively. All above results showed there was no significant difference among the three genotypes (P>0.05).Conclusion:(1) The rate of tumor regression in NPC patients with Gln/Gln genotypes is higher than the other two genotypes at the mid-course and the end of radiotherapy. Its single nucleotide polymorphisms could be a sign of predicting the curative effect at the mid-course and the end of radiotherapy in NPC patients.(2) The the curative effect of radiotherapy in NPC among the three genotypes after 3 months is basically the same, it is mainly related to the clinical stage of nasopharyngeal carcinoma.(3) There is no relativity between the single nucleotide polymorphisms of XRCC1 Codon399 and the acute and chronic irradiation-induced injury in normal tissues.