PDF(Pubmed)
Abstract：
BACKGROUND: The present study was planned to investigate possible association of single nucleotide polymorphisms (SNPs) of nucleotide excision repair (NER) genes such as XPC, XPD, XPG with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from head and neck cancer (HNC) patients receiving radiotherapy. Methods: Two hundred and fifty HNC patients receiving radiotherapy were enrolled in this study and the acute toxicity reactions and radiation response were recorded. Association of SNPs rs2228001 of XPC, rs238406, rs13181 of XPD and rs17655 of XPG gene with normal tissue reactions in the form of dermatitis and mucositis were studied by PCR-RFLP and direct DNA sequencing.
RESULTS: The results of univariate analysis of SNPs of XPC, XPD and XPG showed that XPC polymorphism at codon 939 of exon 15 (A>C) was not associated with dermatitis (OR=0.30, 95% CI: 0.06-1.39; p=0.125), or oral mucositis (OR=1.14, 95% CI: 0.41-3.20; p=0.793). The XPD codon 156 of exon 6 (C>A) and codon 751 of exon-23 A>C) polymorphism showed no association with radiosensitivity in HNC patients (OR=1.50, 95% CI: 0.60-3.71; p=0.080) for dermatitis, (OR=1.54, 95% CI: 0.66-3.61; p=0.312) for oral mucositis. The 1104 Asp variant genotype or allele of XPG (OR=1.35 95% CI: 0.50-3.64; p=0.541) showed no association with degree of radiotherapy associated dermatitis or mucositis (OR=0.80, 95% CI: 0.32-2.03; p=0.648) in HNC patients. The variant C allele of 2920 A/C genotype of XPC gene at codon 939 of exon 15, found protective with developing skin reactions with grade >1 (OR=0.60, 95% CI: 0.36-0.97; p=0.039) in HNC patients treated with radiotherapy.
CONCLUSIONS: The results obtained in this study concluded that the SNPs rs2228001of XPC, rs238406, rs13181 SNPs of XPD and rs17655 SNP of XPG are not associated with normal tissue toxicity in HNC patients treated with radiotherapy. Radiotherapy with high radiation dose was significantly associated with oral mucositis in response to radiotherapy.
RESULTS: The results of univariate analysis of SNPs of XPC, XPD and XPG showed that XPC polymorphism at codon 939 of exon 15 (A>C) was not associated with dermatitis (OR=0.30, 95% CI: 0.06-1.39; p=0.125), or oral mucositis (OR=1.14, 95% CI: 0.41-3.20; p=0.793). The XPD codon 156 of exon 6 (C>A) and codon 751 of exon-23 A>C) polymorphism showed no association with radiosensitivity in HNC patients (OR=1.50, 95% CI: 0.60-3.71; p=0.080) for dermatitis, (OR=1.54, 95% CI: 0.66-3.61; p=0.312) for oral mucositis. The 1104 Asp variant genotype or allele of XPG (OR=1.35 95% CI: 0.50-3.64; p=0.541) showed no association with degree of radiotherapy associated dermatitis or mucositis (OR=0.80, 95% CI: 0.32-2.03; p=0.648) in HNC patients. The variant C allele of 2920 A/C genotype of XPC gene at codon 939 of exon 15, found protective with developing skin reactions with grade >1 (OR=0.60, 95% CI: 0.36-0.97; p=0.039) in HNC patients treated with radiotherapy.
CONCLUSIONS: The results obtained in this study concluded that the SNPs rs2228001of XPC, rs238406, rs13181 SNPs of XPD and rs17655 SNP of XPG are not associated with normal tissue toxicity in HNC patients treated with radiotherapy. Radiotherapy with high radiation dose was significantly associated with oral mucositis in response to radiotherapy.
摘要：
背景：本研究计划调查核苷酸切除修复（NER）基因如XPC的单核苷酸多态性（SNPs）的可能关联，XPD,XPG在接受放射治疗的头颈部癌（HNC）患者的正常组织中具有急性放射引起的毒性，例如皮肤反应和口腔粘膜炎。方法：纳入接受放疗的150例HNC患者，记录其急性毒性反应和放射反应。XPC的SNPsrs2228001的关联，通过PCR-RFLP和直接DNA测序研究了XPD的rs238406，rs13181和XPG基因的rs17655与皮炎和粘膜炎形式的正常组织反应。
结果：XPC单核苷酸多态性的单因素分析结果，XPD和XPG显示外显子15密码子939处的XPC多态性（A>C）与皮炎无关（OR=0.30，95％CI：0.06-1.39；p=0.125），或口腔粘膜炎（OR=1.14，95％CI：0.41-3.20；p=0.793）。外显子6的XPD密码子156（C>A）和外显子23A>C的密码子751）多态性与HNC患者的放射敏感性无关（OR=1.50，95％CI：0.60-3.71；p=0.080）。口腔粘膜炎（OR=1.54，95％CI：0.66-3.61；p=0.312）。在HNC患者中，XPG的1104Asp变异基因型或等位基因（OR=1.3595％CI：0.50-3.64；p=0.541）与放疗相关的皮炎或粘膜炎程度无关（OR=0.80，95％CI：0.32-2.03；p=0.648）。XPC基因第15外显子第939密码子处的2920A/C基因型的变体C等位基因发现，在接受放射治疗的HNC患者中，对发展为>1级的皮肤反应具有保护作用（OR=0.60，95％CI：0.36-0.97；p=0.039）。
结论：本研究中获得的结果得出结论，XPC的SNPrs2228001，rs238406、rs13181SNP的XPD和rs17655SNP的XPG与接受放射治疗的HNC患者的正常组织毒性无关。高辐射剂量的放射治疗与对放射治疗的口腔粘膜炎密切相关。
结果：XPC单核苷酸多态性的单因素分析结果，XPD和XPG显示外显子15密码子939处的XPC多态性（A>C）与皮炎无关（OR=0.30，95％CI：0.06-1.39；p=0.125），或口腔粘膜炎（OR=1.14，95％CI：0.41-3.20；p=0.793）。外显子6的XPD密码子156（C>A）和外显子23A>C的密码子751）多态性与HNC患者的放射敏感性无关（OR=1.50，95％CI：0.60-3.71；p=0.080）。口腔粘膜炎（OR=1.54，95％CI：0.66-3.61；p=0.312）。在HNC患者中，XPG的1104Asp变异基因型或等位基因（OR=1.3595％CI：0.50-3.64；p=0.541）与放疗相关的皮炎或粘膜炎程度无关（OR=0.80，95％CI：0.32-2.03；p=0.648）。XPC基因第15外显子第939密码子处的2920A/C基因型的变体C等位基因发现，在接受放射治疗的HNC患者中，对发展为>1级的皮肤反应具有保护作用（OR=0.60，95％CI：0.36-0.97；p=0.039）。
结论：本研究中获得的结果得出结论，XPC的SNPrs2228001，rs238406、rs13181SNP的XPD和rs17655SNP的XPG与接受放射治疗的HNC患者的正常组织毒性无关。高辐射剂量的放射治疗与对放射治疗的口腔粘膜炎密切相关。
