单核苷酸多态性与肺癌放射性食管炎相关性的研究

Association of single nucleotide polymorphisms with radiation-induced esophagitis

目的探索肺癌放疗中单核苷酸多态性与放射性食管炎的相关性。方法采用聚合酶链反应一限制性内切酶片段长度多态性（PCR—RFLP）方法分析了DNA损伤修复通路、凋亡通路和炎症因子相关的20个基因37个单核苷酸多态性位点的基因型，观察放疗中和放疗结束后3个月内发生的t〉2级放射性食管炎与其相关性。170例病理证实的不可手术的肺癌患者（非小细胞肺癌127例，小细胞肺癌43例）接受了45～70Gy（平均60Gy）的放疗，其中三维适形放疗132例，常规放疗38例；单纯放疗41例，放化疗129例（序贯放化疗78例，同步放化疗51例）。结果170例中发生≥2放射性食管炎40例，其中2级36例，3级4例。单因素分析结果显示放疗技术、同步放化疗与放射性食管炎的发生有关（P=0．032、0．049），多因素分析结果接近统计学水平（P=0．072、0．094）。相关性分析显示TGF—β1-509T和XPD751Lys／Lys基因型为放射性食管炎的风险基因型（Χ^2=5．65，P=0．017，Χ^2=3．84P=0．048）。结论TGF—β1-509C／T和XPDLys751Gin多态性与肺癌放射性食管炎的发生有显著相关性。

Objective To evaluate the relationship between single nucleotide polymorphism（SNP） of candidate genes and radiation-induced esophagitis （RIE） in patients with lung cancer. Methods Between Jan. 2004 and Aug. 2006,170 patients with pathologically diagnosed lung cancer were enrolled in this study. The total target dose was 45-70 Gy（ median 60 Gy）. One hundred and thirty-two patients were treated with three-dimensional conformal radiotherapy（3DCRT） and 38 with two-dimensional radiotherapy（2DRT）. Forty-one patients received radiotherapy alone,78 received sequential chemoradiotherapy and 51 received concurrent chemoradiotherapy. Thirty-seven SNPs in 20 DNA repair genes were analyzed by using PCR- based restricted fragment length polymorphism（RFLP）. These genes were apoptosis and inflammatory cyto- kine genes including ATM, ERCC1, XRCC3, XRCC1, XPD, XPC, XPG, NBS1, STK15, ZNF350, ADPRT, TP53, FAS, FASL, CYP2D6 ＊ 4, CASPASE8, COX2 ,TGF-β, CD14 and ACE. The endpoint was grade≥2 R I E. Results Forty of the 170 patients developed grade t≥ 2 R I E, including 36 in grade 2 and 4 in grade 3. Univariate analysis revealed that radiation technique and concurrent chemoradiotherapy were statistically significant relatives to the incidence of R I E （P = 0. 032 ,0. 049 ） , and both of them had the trend associating with the esophagitis （ P = 0. 072,0. 094）. An increased incidence of esophagitis was observed associating with the TGF-β1-509T and XPD 751Lys/Lys genotypes（Χ^2 =5.65,P =0.017;Χ^2 =3.84,P =0.048） in multivariate analysis. Conclusions Genetic polymorphisms in TGF-β, gene and XPD gene have a significant association with radiation-induced esophagitis.