VHL mutations in renal cell cancer:: does occupational exposure to trichloroethylene make a difference?
VHL mutations in renal cell cancer:: does occupational exposure to trichloroethylene make a difference?
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DOI：
10.1016/j.toxlet.2003.12.074
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发表时间：
2004-06-15
影响因子：
3.5
通讯作者：
Brüning, T
中科院分区：
文献类型：
--
作者：
Brauch, H;Weirich, G;Brüning, T
长期以来，人们一直怀疑职业暴露与肾细胞癌（RCC）的发病率有关。特别是工业溶剂三氯乙烯（TCE）的致癌性在流行病学和分子研究方面一直存在争议。为了进一步阐明这一问题，比较合适的RCC患者组（即tce暴露与非tce暴露患者）显得很重要。我们评估了先前德国研究的RCC，该研究描述了tce暴露患者（n = 17）和非暴露患者（n = 21）之间RCC风险的差异。我们比较了肾癌VHL肿瘤抑制基因的诊断年龄和肿瘤的组织病理学参数以及体细胞突变特征。两组患者的RCC在组织病理学特征上没有差异。我们注意到与未接触tce的患者相比，接触tce的患者诊断年龄更小（P = 0.01）。此外，非tce暴露患者不具有tce暴露患者的体细胞VHL突变特征，如先前发现的热点突变454 C > T P81S或多重突变。这些数据支持了TCE可能导致VHL基因损伤的基因毒性效应，并在高度暴露的受试者中导致RCC的发生。2004爱思唯尔爱尔兰有限公司版权所有。
Occupational exposures have long been suspected to play a role in the incidence of renal cell carcinoma (RCC). Especially, the carcinogenicity of the industrial solvent trichloroethylene (TCE) has been controversially debated, both with respect to the epidemiological and the molecular studies. In order to further elucidate this issue, it appeared important to compare suitable RCC patient groups, i.e., TCE-exposed versus non-TCE-exposed patients. We evaluated RCC from a previous German study that had described differences in RCC risks between TCE-exposed (n = 17) and non-exposed patients (n = 21). We compared age at diagnosis and histopathologic parameters of tumors as well as somatic mutation characteristics in the kidney cancer causing VHL tumor suppressor gene. RCC did not differ with respect to histopathological characteristics in both patient groups. We noticed a younger age at diagnosis in TCE-exposed patients compared to non-exposed patients (P = 0.01). Moreover, the non-TCE-exposed patients did not share the somatic VHL mutation characteristics of TCE-exposed patients such as the previously identified hot spot mutation 454 C > T P81S or multiple mutations. These data support the notion of a putative genotoxic effect of TCE leading to VHL gene damage and subsequent occurrence of RCC in highly exposed subjects. (C) 2004 Elsevier Ireland Ltd. All rights reserved.