Hayes R B
Epidemiology and Biostatistics Program, U.S. National Cancer Institute, Bethesda, MD 20895, USA.
Med Lav. 1995 May-Jun;86(3):206-13.
This review describes statistical models for the biological interaction of susceptibility genes and environmental exposures, as observed in epidemiologic studies. The importance of metabolic transformation of industrial carcinogens and the potential role of genetic polymorphisms in metabolic enzyme activity are outlined. Several genetic polymorphisms have been associated with cancer risk, but the link with the relevant exposures has only infrequently been specified. For example, studies show that slow N-acetylation increased bladder cancer risk among workers exposed to some arylamines, as found among dye workers in England, but that this effect does not hold for benzidine exposure. This link of a genetic susceptibility factor with cancer risk due to some aromatic amines, but not to others, illustrated the specific nature of metabolic environment/gene interactions. Epidemiologic studies to investigate the role of genetic susceptibility in cancer development promise to further the identification of human carcinogens by focusing on susceptible individuals and, in turn, to enhance understanding of human cancer by relating cancer risk in populations to underlying biologic processes. Occupational studies are key to this effort.
本综述描述了在流行病学研究中观察到的易感性基因与环境暴露之间生物学相互作用的统计模型。概述了工业致癌物代谢转化的重要性以及基因多态性在代谢酶活性中的潜在作用。几种基因多态性与癌症风险相关,但与相关暴露的联系很少被明确指出。例如,研究表明,慢N-乙酰化增加了接触某些芳胺的工人患膀胱癌的风险,如在英国染料工人中发现的那样,但这种效应在联苯胺暴露中并不成立。这种遗传易感性因素与某些芳香胺而非其他芳香胺导致的癌症风险之间的联系,说明了代谢环境/基因相互作用的特殊性。旨在研究遗传易感性在癌症发生中作用的流行病学研究,有望通过关注易感个体来进一步识别人类致癌物,进而通过将人群中的癌症风险与潜在生物学过程联系起来,增进对人类癌症的理解。职业研究是这项工作的关键。