Department of Radiation, Cross Cancer Institute, Edmonton, Alberta, Canada.
Semin Radiat Oncol. 2010 Oct;20(4):232-40. doi: 10.1016/j.semradonc.2010.05.003.
Radiation therapy is a key modality in the treatment of cancer. Substantial progress has been made in unraveling the molecular events which underpin the responses of malignant and surrounding normal tissues to ionizing radiation. An understanding of the genes involved in processes such as DNA double-strand break repair, DNA damage response, cell-cycle control, apoptosis, cellular antioxidant defenses, and cytokine production, has evolved toward examination of how genetic variants, most often, single nucleotide polymorphisms (SNPs), may influence interindividual radioresponse. Experimental approaches, such as candidate SNP-association studies, genome-wide association studies, and massively parallel sequencing are being proposed to address these questions. We present a focused review of the evidence supporting an association between SNPs in DNA repair genes and radioresponse in normal tissues and tumors. Although preliminary results indicate possible associations, there are methodological weaknesses in many of the studies, and independent validation of SNPs as biomarkers of radioresponse in much larger cohorts will likely require research cooperation through international consortia.
放射治疗是癌症治疗的一种主要方式。在揭示导致恶性肿瘤和周围正常组织对电离辐射产生反应的分子事件方面，已经取得了重大进展。人们对涉及 DNA 双链断裂修复、DNA 损伤反应、细胞周期控制、细胞凋亡、细胞抗氧化防御和细胞因子产生等过程的基因的理解，已经发展到研究遗传变异（最常见的是单核苷酸多态性 SNPs）如何影响个体之间的放射反应。实验方法，如候选 SNP 关联研究、全基因组关联研究和大规模平行测序，正被提议用来解决这些问题。我们对支持 DNA 修复基因中的 SNP 与正常组织和肿瘤的放射反应之间存在关联的证据进行了重点回顾。尽管初步结果表明可能存在关联，但许多研究存在方法学上的弱点，并且需要通过国际联盟进行更大规模队列的独立验证，才能将 SNPs 确定为放射反应的生物标志物。
