Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM -: a study based on DNA from formalin fixed paraffin embedded tissue samples
Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM -: a study based on DNA from formalin fixed paraffin embedded tissue samples
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DOI：
10.1080/09553000600876637
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发表时间：
2006-08-01
影响因子：
2.6
通讯作者：
Overgaard, J.
中科院分区：
文献类型：
--
作者：
Andreassen, C. N.;Alsner, J.;Overgaard, J.
目的：在先前发表的两项研究中，发现TGFB 1（转化生长因子β 1基因）、XRCC 1（X射线修复交叉互补1基因）、XRCC 3（X射线修复交叉互补3基因）、SOD 2（锰超氧化物歧化酶基因）和ATM（共济失调毛细血管扩张症突变基因）的单核苷酸多态性（SNP）与辐射诱导的皮下纤维化风险相关。本研究进行，以寻求这些findings.Materials和方法的确认：像以前调查的41例患者，包括在本研究中的120名受试者是从319个乳房切除术后放疗患者的历史队列累计。所有患者均接受大分割放射治疗。TGFB 1第7509位，密码子10和25，XRCC 1密码子194、280和399，XRCC 3密码子241，SOD 2密码子16，ATM密码子1853和APEX（脱嘌呤/脱嘧啶核酸外切酶基因）密码子148多态性基于存档的组织学材料进行评估。从剂量反应assessments.Results的纤维化风险的差异进行了量化：没有一个调查的多态性，皮下纤维化的风险显着关联进行了观察。一个详细的分析并没有发现任何明显的解释以前和本study.Conclusion之间的差异：以前观察到的协会与辐射引起的皮下纤维化的风险不能复制在本研究中。需要进一步的研究来阐明遗传变异对正常组织放射敏感性的影响。
Purpose: In two previously published studies, associations with risk of radiation-induced subcutaneous fibrosis were found for single nucleotide polymorphisms (SNP) in TGFB1 (transforming growth factor beta 1 gene), XRCC1 (X-ray repair cross-complementing 1 gene), XRCC3 (X-ray repair cross-complementing 3 gene), SOD2 (manganese superoxide dismutase gene) and ATM (gene of ataxia telangiectasia mutated). The present study was conducted to seek a confirmation of these findings.Materials and methods: Like the 41 patients previously investigated, the 120 subjects included in the present study were accrued from a historical cohort of 319 post-mastectomy radiotherapy patients. All patients received hypo-fractionated radiotherapy. The TGFB1 position 7509, codons 10 and 25, XRCC1 codons 194, 280 and 399, XRCC3 codon 241, SOD2 codon 16, ATM codon 1853 and APEX (apurinic/apyrimidinic exonuclease gene) codon 148 polymorphisms were assessed based on archival histological material. Differences in fibrosis risk were quantified from dose-response assessments.Results: For none of the investigated polymorphisms, significant associations with risk of subcutaneous fibrosis were observed. A detailed analysis did not reveal any obvious explanation for the discrepancy between the previous and the present study.Conclusion: The previously observed associations with risk of radiation-induced subcutaneous fibrosis could not be replicated in the present study. Further studies are needed to elucidate the influence of genetic variation upon normal tissue radiosensitivity.