Department of Oncology, Krishna Vishwa Vidyapeeth "Deemed to be University", Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.
Krishna Institute of Allied Sciences, Krishna Vishwa Vidyapeeth "Deemed to be University", Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.
Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2645-2654. doi: 10.31557/APJCP.2024.25.8.2645.
Radiotherapy (RT) is a crucial treatment for head and neck cancer however, it causes adverse reactions to the normal tissue and organs adjacent to target tumor. The present study was carried out to investigate possible association of single nucleotide polymorphism in DNA repair genes with toxicity effects of radiotherapy on normal tissue.
Three hundred and fifty head and neck cancer patients receiving radiotherapy treatment were enrolled in this study. The adverse after effects of radiotherapy on the normal tissue in the form of skin reactions were recorded. Single nucleotide polymorphisms of APE1 (rs1130409), hOGG1 (rs1052133) and Rad51 (rs1801320, rs1801321) genes were studied by polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing methods and their association with development of severe radio-toxicity effects was evaluated logistic regression analysis.
The 172G/T polymorphism of Rad51 was 2.85 times higher and significantly associated with skin reactions (OR=2.85, 95% CI: 1.50-5.41; p=0.001) and severe oral mucositis (OR=4.96, 95% CI: 2.40-10.25; p<0.0001). These results suggested that the polymorphic nature of Rad51 is responsible for risk of radiotherapy adverse effects in HNC patients. The variant 326Cys and heterozygous 326Ser/Cys genotype of hOGG1 was significantly associated with high tumor grade (OR=3.16 95% CI: 1.66-5.99; p=0.0004, and OR=3.97 95% CI: 2.15-7.34; p=<0.0001 respectively). The homozygous variant 172TT genotype of Rad51 showed positive association with poor response of both tumor and nodes towards radiotherapy treatment (p=0.007 and p=0.022).
Interpretation of our results revealed significant association of rs1801321 SNP of Rad51 with development of adverse toxicity reactions in normal tissue of head and neck cancer patients treated with radiotherapy.
放射治疗（RT）是头颈部癌症的重要治疗方法，但会对靶肿瘤相邻的正常组织和器官产生不良反应。本研究旨在探讨 DNA 修复基因的单核苷酸多态性与放射治疗对正常组织毒性作用的可能关联。
本研究纳入了 350 名接受放射治疗的头颈部癌症患者。记录放射治疗后正常组织的不良反应。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和直接 DNA 测序方法研究 APE1（rs1130409）、hOGG1（rs1052133）和 Rad51（rs1801320、rs1801321）基因的单核苷酸多态性，并采用逻辑回归分析评估其与严重放射毒性作用发生的关系。
Rad51 的 172G/T 多态性增加了 2.85 倍，与皮肤反应（OR=2.85，95%CI：1.50-5.41；p=0.001）和严重口腔粘膜炎（OR=4.96，95%CI：2.40-10.25；p<0.0001）显著相关。这些结果表明，Rad51 的多态性与 HNC 患者放射治疗不良反应的风险有关。hOGG1 的 326Cys 变体和杂合 326Ser/Cys 基因型与高肿瘤分级显著相关（OR=3.16，95%CI：1.66-5.99；p=0.0004，OR=3.97，95%CI：2.15-7.34；p<0.0001）。Rad51 的纯合变体 172TT 基因型与肿瘤和淋巴结对放射治疗的反应不良呈正相关（p=0.007 和 p=0.022）。
本研究结果表明，Rad51 的 rs1801321 单核苷酸多态性与放射治疗头颈部癌症患者正常组织不良反应的发生有显著关联。
