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研究单核苷酸多态性与¹²⁵I前列腺近距离放射治疗植入物所致泌尿毒性的相关性。

Single-nucleotide polymorphisms studied for associations with urinary toxicity from (125)I prostate brachytherapy implants.

作者信息

Usmani Nawaid, Leong Nelson, Martell Kevin, Lan Lanna, Ghosh Sunita, Pervez Nadeem, Pedersen John, Yee Don, Murtha Albert, Amanie John, Sloboda Ron, Murray David, Parliament Matthew

机构信息

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

出版信息

Brachytherapy. 2014 May-Jun;13(3):285-91. doi: 10.1016/j.brachy.2014.02.002. Epub 2014 Mar 18.

Abstract

PURPOSE

To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant.

METHODS AND MATERIALS

Genomic DNA from 296 men treated with (125)I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes (TP53, ERCC2, GSTP1, NOS, TGFβ1, MSH6, RAD51, ATM, LIG4, XRCC1, XRCC3, GSTA1, and SOD2) were tested in this cohort for correlations with toxicity.

RESULTS

This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age (p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis.

CONCLUSIONS

This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach.

摘要

目的

确定与¹²⁵I前列腺近距离治疗植入术后晚期泌尿系统毒性相关的临床、剂量学和遗传因素。

方法和材料

本研究从296例接受¹²⁵I前列腺近距离治疗单药治疗的男性唾液样本中提取基因组DNA。汇编了一个回顾性数据库,包括该队列患者的临床、剂量学和毒性数据。对来自13个基因(TP53、ERCC2、GSTP1、NOS、TGFβ1、MSH6、RAD51、ATM、LIG4、XRCC1、XRCC3、GSTA1和SOD2)的14个候选单核苷酸多态性(SNP)在该队列中进行毒性相关性测试。

结果

本研究确定了217例至少随访2年的男性。其中,39例患者出现≥2级晚期泌尿系统并发症,包括经尿道前列腺切除术、尿道狭窄、肉眼血尿或国际前列腺症状评分持续增加。与晚期泌尿系统毒性相关的唯一临床或剂量学因素是年龄(p = 0.02)。在单因素分析中,本研究测试的14个SNP均与晚期泌尿系统毒性无关。

结论

本研究确定年龄是与晚期泌尿系统毒性相关的唯一变量。然而,本研究中样本量小以及采用的候选基因方法意味着进一步的研究至关重要。全基因组关联研究正在成为未来放射基因组学研究的首选方法,以克服候选基因方法的局限性。

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