修复基因XRCC3和HOGG1单核苷酸多态性与食管鳞癌放射敏感性相关性研究

A correlation study of single nucleotide polymorphisms in XRCC3 , HOGG1 gene of repair DNA and radiosensitivity in esophageal squamous cell carcinoma

目的研究DNA修复基因X线交错互补修复组-3（XRCC3）、人类8-羟基鸟嘌呤糖苷酶-1（HOGG1）单核苷酸多态性与食管鳞状细胞癌放射敏感性关系。方法采用聚合酶链反应-限制性片段长度多态性方法检测199例食管鳞状细胞癌患者外周血XRCC3、HOGG1基因单核苷酸多态性，结合临床资料分析XRCC，Thr241Met、HOGG1Ser326Cys单核苷酸多态性与放疗近期疗效和不良反应的关系。结果199例食管鳞癌患者根治性放疗有效率为81．4％，其中携带XRCC，Thr／Met基因型的高于Thr／Thr型的（91．5％：77．1％，x2=5．67，P=0．017），携带HOGG1Ser／Ser、Ser／Cys、Cys／Cys型的相似（74．1％、84．2％、83．9％，x2=2．64，P=0．268）。携带XRCC3Thr／Met基因型的放射性食管损伤发生率高于Thr／Thr型的（35．6％：20．0％，x2=5．44，P=0．020），携带HOGG1Ser／Ser、Ser／Cys、Cys／Cys型的相似（24．1％、24．6％、25．8％，x2=0．03，P=0．984）。Logistic多因素分析显示XRCC，基因多态性是影响放疗近期疗效及急性放射性食管损伤发生的独立因素（X2=16．12、4．43，P=0．009、0．035），而HOGG1基因多态性与其无关（x2=3．74、0．58，P=0．053、0．445）。结论XRCC3Thr／Met基因单核苷酸多态性与食管癌放射敏感性相关，有可能作为预测放疗近期疗效和不良反应的参考指标之一。

Objective To study the relationship between the single nucleotide polymorphisms （SNP） of X-ray repair cross-complementing group-3 （ XRCC3 ） , human 8-hydroxyguanine glycosylase-1 （ HOGG1 ） gene of repair DNA and the radiosensitivity in esophageal squamous cell carcinoma （ ESCC ）. Methods Genome DNA was exraeted from whole blood cells of ESCC patients. XRCC3 and HOGG1 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method. The relationship was analyzed between SNP of XRCC3 Thr241 Met, HOGG1Ser326 Cys and the response to radiotherapy in ESCC. Results Totally 199 ESCC patients were treated with radical radiotherapy. The response rate was 81.4%. The response rate in patients with the XRCC3Thr / Met genotype was significant higher than that in patients with Thr / Thr genotype （91.5% vs 77. 1% ,X2 =5.67,P =0. 017） ,with the same in HOGG1 Set / Ser, Ser / Cys and Cys / Cys genotype （74. 1% , 84. 2% , 83.9% , X2 = 2. 64, P = 0. 268）. The esophageal radioactivity injury rate in patients with the XRCC3Thr / Met genotype was also significant higher than that in patients with Thr / Thr genotype （35.6% vs 20. 0%, X2= 5.44, P = 0.020）, with the same in HOGG1Ser / Ser, Ser / Cys and Cys / Cys genotype （24. 1% ,24.6%, 25.8% ,X2 =0. 03,P=0. 984）. In logistic multivariate analysis, the SNP of XRCC3 was the independent influencing factor closely correlating with the radiosensitivity of esophageal cancer （X2 = 16. 12,4.43, P = 0.009,0. 035）. No significant difference was observed between the SNP in HOGG1Ser326 Cys and the response rate of radiotherapy or the rate of esophageal radioactivity injury （ X2 = 3. 7 4 , 0. 5 8 , P = 0. 0 5 3 ,0. 445）. Conclusions SNP of XRCC3Thr/Met is associated with the radiosensitivity in ESCC patients, which suggests that the XRCC3Thr/Met SNP may be a predictor for ESCC patients who likely to response to radiotherapy.