Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer
Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer
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DOI：
10.1158/1078-0432.ccr-05-2703
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发表时间：
2006-04-15
影响因子：
11.5
通讯作者：
Parliament, M
中科院分区：
文献类型：
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作者：
Damaraju, S;Murray, D;Parliament, M
目的：探讨编码DNA损伤识别/修复/反应和类固醇代谢蛋白的候选基因中的单核苷酸多态性（SNP）与既往接受三维适形放射治疗（3-DCRT）的前列腺癌患者的回顾性队列中的临床放射毒性之间的可能关系。1996年9月至2000年12月，124例前列腺癌患者在我院接受了3-DCRT。其中，83人同意随访血液采样和SNP分析。28名患者在至少一次随访时记录为发生≥ 2级晚期膀胱或直肠毒性（放射治疗肿瘤组评分系统）。我们使用焦磷酸测序技术分析了BRCA 1、BRCA 2、ESR 1、XRCC 1、XRCC 2、XRCC 3、NBN、RAD 51、RAD 52、LIG 4、ATM、BCL 2、TGFB 1、MSH 6、ERCC 2、XPF NR 3C 1、CYP 1A 1、CYP 2C 9、CYP 2C 19、CYP 3A 5、CYP 2D 6、CYP 11B 2和CYP 17 A1基因中的49个SNP。与晚期直肠或膀胱毒性的显着单变量相关XRCC 3（A）G 5'非翻译区NT 4541）、LIG 4（T>C Asp（568）Asp）、MLH 1（C）T、瓦尔（219）Ile）、CYP 2D6 *4（G>A剪接缺陷），平均直肠和膀胱剂量，直肠或膀胱30%的剂量，以及年龄C，Asp（568）Asp），ERCC 2（G>A，Asp（711）Asp），CYP2D6*4（G>A，剪接缺陷），平均膀胱剂量>60戈伊，直肠体积30%的剂量>75戈伊。在这项研究中，我们确定了LIG 4，ERCC 2，和CYP 2D 6基因作为推定的标志物，以预测个体在前列腺癌放射治疗引起的并发症的风险。
Objective: To explore the possible relationship between single nucleotide polymorphisms (SNP) in candidate genes encoding DNA damage recognition/repair/response and steroid metabolism proteins with respect to clinical radiation toxicity in a retrospective cohort of patients previously treated with three-dimensional conformal radiotherapy (3-DCRT) for prostate cancer.Experimental Design: One hundred twenty-four patients with prostate cancer underwent 3-DCRT at our institution between September 1996 and December 2000. Of these, 83 consented for follow-up of blood sampling and SNP analysis. Twenty-eight patients were documented as having experienced grade >= 2 late bladder or rectal toxicity (scoring system of Radiation Therapy Oncology Group) on at least one follow-up visit. We analyzed 49 SNPs in BRCA1, BRCA2, ESR1, XRCC1, XRCC2, XRCC3, NBN, RAD51, RAD52, LIG4, ATM, BCL2, TGFB1, MSH6, ERCC2, XPF NR3C1, CYP1A1, CYP2C9, CYP2C19, CYP3A5, CYP2D6, CYP11B2, and CYP17A1 genes using the Pyrosequencing technique.Results: Significant univariate associations with late rectal or bladder toxicity (grade >= 2) were found for XRCC3 (A)G 5' untranslated region NT 4541), LIG4 (T>C Asp (568)Asp), MLH1 (C)T, Val(219)Ile), CYP2D6*4 (G>A splicing defect), mean rectal and bladder dose, dose to 30% of rectum or bladder, and age C, Asp(568)Asp), ERCC2 (G>A, Asp(711)Asp), CYP2D6*4 (G>A, splicing defect), mean bladder dose >60 Gy, and dose to 30% of rectal volume >75 Gy.Conclusions: In this study, we identified SNPs in LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk for complications arising from radiation therapy in prostate cancer.