TGFβ1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors
TGFβ1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors
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DOI：
10.1016/j.ijrobp.2006.03.047
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发表时间：
2006-07-15
影响因子：
7
通讯作者：
Thierens, Hubert
中科院分区：
文献类型：
--
作者：
De Ruyck, Kim;Van Eijkeren, Marc;Thierens, Hubert
目的：探讨6种转化生长因子β 1基因与乳腺癌的关系。（TGF β 1）多态性（-1.552delAG，-800G> A，-509C> T，Leu10Pro，Arg25Pro，Thr263IIe）和妇科放射治疗（RT）后晚期正常组织反应的发生。78名患有宫颈癌或子宫内膜癌的妇女和140名对照者被纳入研究。根据不良事件通用术语标准3.0版（CTCAEv3.0）量表，25例患者出现晚期不良反应（CTC 2+），其中11例出现严重并发症（CTC 3+）。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）、单碱基延伸和基因分型方法检测TGF β 1基因多态性位点。结果：-1.552delAGG、-509TT和10Pro纯合子基因型与发生晚期严重RT反应的风险相关。三重（变异）纯合子患者发生严重RT反应的风险增加3.6倍（p = 0.26）。-800 A等位基因、251 'ro等位基因或2631' le等位基因与临床放射敏感性无关。-1.552delAGG与-509C> T多态性之间存在完全连锁不平衡（LD），-1.552/-509与Leu10Pro多态性之间存在紧密连锁不平衡。单倍型分析揭示了两个主要的单倍型，但不能区分从nonradiosensitive patients.Conclusions：本研究表明，纯合子变体TGF β 1-1.552delAGG，-509TT，和10Pro基因型可能与妇科RT后严重的临床放射敏感性。
Purpose: To investigate the association between six transforming growth factor beta 1 gene (TGF beta 1) polymorphisms (-1.552delAGG, -800G > A, -509C > T, Leu10Pro, Arg25Pro, Thr263IIe) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT).Methods and Materials: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites in TGF beta 1.Results: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p = 0.26). Neither the -800A allele, nor the 251'ro allele or the 2631[le allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients.Conclusions: The present study shows that homozygous variant TGF beta 1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT. (c) 2006 Elsevier Inc.