Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation
Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation
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DOI：
10.2217/14622416.7.1.67
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发表时间：
2006-01-01
期刊：
影响因子：
2.1
通讯作者：
Lenz, HJ
中科院分区：
文献类型：
--
作者：
Gordon, MA;Gil, J;Lenz, HJ
目的：直肠II期和III期腺癌的总体5年生存率约为50%，尽管通过化疗和放疗改善了局部控制，但肿瘤复发仍然是一个主要问题。由于临床反应和宿主毒性的个体差异，放化疗的疗效可能会显著降低。因此，必须确定哪些患者将受益于放化疗，哪些患者将复发。在这项研究中，我们测试了参与癌症进展关键途径（即药物代谢、肿瘤微环境、细胞周期调节和DNA修复）的18个基因的21种多态性的特定模式是否可以预测直肠癌放化疗患者肿瘤复发的风险。患者和方法：共90例接受放化疗的II期或III期直肠癌患者，采用基于聚合酶链反应（PCR）的技术对21个多态性进行基因分型。结果：白细胞介素(IL)-8多态性与复发风险单独相关。对所有多态性和临床变量进行分类和回归树分析，得出风险树，包括以下变量：淋巴结状态、IL-8、细胞内粘附分子-1、转化生长因子- β P和成纤维细胞生长因子受体4。结论：基因组分析可能有助于识别肿瘤复发的高风险患者，以及那些更有可能从放化疗中获益的患者。需要更大的前瞻性研究来验证这些初步数据，使用生殖系多态性对直肠癌放化疗患者肿瘤复发的影响。
Purpose: Stage II and III adenocarcinoma of the rectum has an overall 5-year survival rate of approximately 50%, and tumor recurrence remains a major problem despite an improvement in local control through chemotherapy and radiation. The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity. Therefore, it is imperative to identify those patients who will benefit from chemoradiation therapy and those who will develop recurrent disease. In this study, we tested whether a specific pattern of 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (i.e., drug metabolism, tumor microenvironment, cell cycle regulation, and DNA repair) will predict the risk of tumor recurrence in rectal cancer patients treated with chemoradiation. Patients and methods: A total of 90 patients with Stage II or III rectal cancer treated with chemoradiation were genotyped using polymerase chain reaction (PCR)-based techniques for 21 polymorphisms. Results: A polymorphism in interleukin (IL)-8 was individually associated with risk of recurrence. Classification and regression tree analysis of all polymorphisms and clinical variables developed a risk tree including the following variables: node status, IL-8, intracellular adhesion molecule-1, transforming growth factor-beta P, and fibroblast growth factor receptor 4. Conclusion: Genomic profiling may help to identify patients who are at high risk for developing tumor recurrence, and those who are more likely to benefit from chemoradiation therapy. A larger prospective study is needed to validate these preliminary data using germline polymorphisms on tumor recurrences in rectal cancer patients treated with chemoradiation.