Perera F P, Santella R M, Brenner D, Young T L, Weinstein I B
School of Public Health, Columbia University, New York, NY.
IARC Sci Publ. 1988(89):451-9.
Lung cancer is now the major cause of cancer deaths in the USA and is an increasingly significant cancer worldwide. Biological markers could be used to prevent lung cancer by allowing more timely and precise understanding of the role of environmental factors. So far, biological markers that can serve as carcinogen dosimeters have been investigated in only a small number of pilot studies of populations with current or past exposure to lung carcinogens. We describe several of our collaborative studies involving smokers, various worker populations, lung cancer cases and controls in order to illustrate the advantages and the limitations of 'molecular epidemiology'. The enzyme-linked immunosorbent assay (ELISA) with antibodies to polycyclic aromatic hydrocarbon (PAH)-DNA adducts has been used in conjunction with one or more of the following: physicochemical techniques to monitor carcinogen adducts on haemoglobin, cytogenetic methods to quantify sister chromatid exchange (SCE) and chromosomal aberrations, and Southern and western blot analyses of oncogene activation. Increased levels of markers of biologically effective doses have generally been seen in exposed and high-risk groups when compared to controls. We have also observed significant background levels of such markers and interindividual variation in levels of certain biological markers resulting from exposures to carcinogens. Thus, these methods may be particularly useful in identifying segments of the population that have received a significant effective dose and hence can be considered to be at elevated risk of cancer. Such studies are necessary to validate laboratory methods and lay the groundwork for more definitive molecular epidemiological investigations of lung cancer.
肺癌目前是美国癌症死亡的主要原因，并且在全球范围内，其作为一种癌症的重要性日益凸显。生物标志物可通过使人们更及时、精确地了解环境因素的作用，来用于预防肺癌。到目前为止，仅在少数针对当前或过去接触肺部致癌物人群的试点研究中，对可作为致癌物剂量计的生物标志物进行了调查。我们描述了我们的几项合作研究，涉及吸烟者、各类工人人群、肺癌病例及对照，以阐明“分子流行病学”的优势与局限性。针对多环芳烃（PAH）-DNA加合物的抗体酶联免疫吸附测定（ELISA）已与以下一种或多种方法结合使用：监测血红蛋白上致癌物加合物的物理化学技术、定量姐妹染色单体交换（SCE）和染色体畸变的细胞遗传学方法，以及癌基因激活的Southern和western印迹分析。与对照组相比，暴露组和高危组中生物有效剂量标志物的水平通常有所升高。我们还观察到了此类标志物的显著背景水平，以及因接触致癌物导致的某些生物标志物水平的个体间差异。因此，这些方法在识别接受了显著有效剂量、因而可被视为癌症风险升高的人群部分时可能特别有用。此类研究对于验证实验室方法以及为更确切的肺癌分子流行病学调查奠定基础而言是必要的。
