Nucleotide excision repair gene polymorphisms may predict acute toxicity in patients treated with chemoradiotherapy for bladder cancer
Nucleotide excision repair gene polymorphisms may predict acute toxicity in patients treated with chemoradiotherapy for bladder cancer
复制标题
DOI：
10.2217/pgs.10.106
复制
发表时间：
2010-10-01
期刊：
影响因子：
2.1
通讯作者：
Matsuyama, Hideyasu
中科院分区：
文献类型：
--
作者：
Sakano, Shigeru;Hinoda, Yuji;Matsuyama, Hideyasu
目的：以铂为基础的化学放射治疗（CRT）作为膀胱保护治疗已显示出对肌肉浸润性膀胱癌有希望的结果。然而，治疗相关毒性仍然是治疗计划中的主要考虑因素。据报道，参与DNA修复（编码修复铂剂和电离辐射损伤的DNA的酶）的基因中的一些常见多态性导致修复能力的调节。我们研究了参与DNA修复的功能性遗传多态性与CRT急性毒性之间的关系，以确定这些多态性对毒性的预测价值。材料和方法：研究组包括101名接受含铂CRT治疗的膀胱癌患者，XPC中有7个多态性。（Lys939Gln，rs2228001），XPD（Lys751Gln，rs13181），XPG基因分型包括Asp1104His，rs17655，XRCC1（Arg399Gln，rs25487），XRCC3（Thr241Met，rs861539），TP53（Arg72Pro，rs1042522）和MDM2（5NP309，T> G，rs2279744）。结果如下：核苷酸切除修复基因中两个以上的总变异等位基因，包括XPC、XPD和XPG，与3级或4级中性粒细胞减少症显著相关（校正比值比[aOR]：6.8; 95% CI：2.0 - 26; p = 0.0026）。任何基因型与2级或以上恶心/呕吐或腹泻之间均无显著相关性。与Lys/Lys相比，任何3级或4级血液学毒性与XPC的Gln/Gln或Lys/Gln + Gln/Gln基因型显著相关（aOR：10; 95% CI：2.0 - 65; p = 0.0070或aOR：6.3; 95% CI：1.9 - 29; p = 0.0069）。结论：这些结果表明，核苷酸切除修复基因多态性，特别是在XPC，可能是潜在的预测因素CRT的急性毒性膀胱癌，帮助个体患者选择膀胱保护治疗。然而，需要更大样本量的进一步研究才能得出最终结论。
Aims: Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, treatment-related toxicity remains a major consideration in therapeutic planning. Some common polymorphisms in genes involved in DNA repair (encoding enzymes that repair DNA damaged by platinum agents and ionizing radiation) are reported to result in modulation of the repair capacity. We investigated associations between functional genetic polymorphisms involved in DNA repair and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity. Materials & methods: The study group comprised of 101 bladder cancer patients treated with platinum-based CRT, and seven polymorphisms in XPC (Lys939Gln, rs2228001), XPD (Lys751Gln, rs13181), XPG (Asp1104His, rs17655), XRCC1 (Arg399Gln, rs25487), XRCC3 (Thr241Met, rs861539), TP53 (Arg72Pro, rs1042522) and MDM2 (5NP309, T>G, rs2279744) were genotyped. Results: More than two total variant alleles in nucleotide excision repair genes, including XPC, XPD and XPG, were significantly associated with grade 3 or 4 neutropenia (adjusted odds ratio [aOR]: 6.8; 95% CI: 2.0-26; p = 0.0026). There were no significant associations between any genotypes and grade 2 or greater nausea/vomiting or diarrhea. Any grade 3 or 4 hematological toxicity was significantly associated with the Gln/Gln or Lys/Gln + Gln/Gln genotypes of XPC compared with Lys/Lys (aOR: 10; 95% CI: 2.0-65; p = 0.0070 or aOR: 6.3; 95% CI: 1.9-29; p = 0.0069; respectively). Conclusion: These results suggest that nucleotide excision repair gene polymorphisms, especially in XPC, might potentially be predictive factors for acute toxicity of CRT for bladder cancer, helping individual patient selection for bladder conservation therapy. However, further studies with larger sample sizes are needed to draw final conclusions.