Li Y, Chen Y, Slavkovic V, Ahsan H, Parvez F, Graziano J H, Brandt-Rauf P W
Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Biomarkers. 2007 May-Jun;12(3):256-65. doi: 10.1080/13547500601133939.
Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p<or=0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p <or= 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions.
表皮生长因子受体依赖性机制已被认为参与了促成癌症发展的生长信号转导途径，包括皮肤癌发生。血清中表皮生长因子受体（EGFR ECD）细胞外结构域的检测已被提议作为监测体内这种效应的潜在生物标志物。砷是一种已知的人类致癌物，在通过饮用水接触砷的人群中会引发皮肤和其他恶性肿瘤。我们多年来一直在研究的一个此类受暴露人群位于孟加拉国。本研究的目的是检测EGFR ECD作为该人群砷暴露和/或效应的潜在生物标志物。通过酶联免疫吸附测定法测定了来自孟加拉国阿拉伊扎尔地区574名饮用水砷暴露程度不同的个体血清样本中的EGFR ECD水平。在多元回归分析中，发现血清EGFR ECD与三种不同的砷暴露测量指标（井水砷、尿砷和累积砷指数）呈正相关，且具有统计学显著水平（p≤0.034），这种关联在有砷诱导皮肤病变的个体中最为强烈（p≤0.002）。当研究对象按血清EGFR ECD水平三分位数分层时，随着所有三种砷测量指标（也按三分位数分层）的每一次增加，皮肤病变风险逐渐增加，且在EGFR ECD水平最高三分位数的受试者中，这种增加的风险更为明显。这些结果表明，血清EGFR ECD水平可能是砷暴露效应的潜在生物标志物，并且可能表明那些砷诱导皮肤病变发生风险最高的暴露个体。
