The impact of pharmacogenetics on radiation therapy outcome in cancer patients. A focus on DNA damage response genes

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• 作者：Delphine Borchiellini^a ; ^b ; ^d ; ^{delphinebor@wanadoo.fr} ; Marie-Christine Etienne-Grimaldi^a ; ^e ; ^{marie-christine.etienne@nice.unicancer.fr} ; Juliette Thariat^c ; ^f ; ^{jthariat@hotmail.com} ; Gé ; rard Milano^a ; ^{gerard.milano@nice.unicancer.fr}
• 关键词：Single nucleotide polymorphism ; Gene ; Cancer ; Radiation therapy/radiotherapy ; DNA repair ; Apoptosis ; Cell-cycle
• 刊名：Cancer Treatment Reviews
• 出版年：2012
• 期刊代码：44_03057372
• 类别：med
• 出版时间：October, 2012
• 卷：38
• 期：6
• 页码：737-759
• 文件大小：849 K

摘要

More than half of cancer patients are treated by radiation therapy, with a wide inter-patient variability in tumour response. Recent advances have been made in understanding molecular mechanisms that govern the behaviour of tumour cells and tissues exposed to ionizing radiation. Accumulating data suggest an important role of DNA damage response genes, including DNA repair (especially double-strand breaks), apoptosis and cell-cycle control genes. It has been hypothesized that frequent germinal polymorphisms, most often single-nucleotide polymorphisms, in DNA damage response genes may impact tumour response and clinical outcome for patients receiving a radiotherapy-based treatment. We reviewed literature covering the relationships between candidate gene polymorphisms in DNA damage response and the efficacy of a radiation-based treatment. Although several methodological limitations may preclude a definitive conclusion, single nucleotide polymorphisms of several candidate genes such as ERCC- or XRCC-family genes seem to be potential predictive biomarkers of radiotherapy efficacy, even though not strictly involved in radiotherapy-induced double-strand breaks repair. In order to improve the relevance of clinical results, and our interpretation of them, we draw a parallel between clinical findings and available preclinical data on polymorphism functionality. Clinical findings require validation in larger replication studies and open the prospect of future clinical trials.