Taioli E, Zocchetti C, Garte S
Nelson Institute of Environmental Medicine and Kaplan Cancer Center, New York University Medical Center, New York, NY 10010, USA.
Environ Health Perspect. 1998 Feb;106(2):67-70. doi: 10.1289/ehp.9810667.
Polymorphic metabolic genes that confer enhanced genetic susceptibility to the carcinogenic effects of certain environmental carcinogens act according to a type 2 interaction between genetic and environmental risk factors. This type of interaction, for which the gene has no effect on disease outcome by itself but only modifies the risk associated with exposure, must be treated differently from other types of gene-environment interaction. We present a method to analyze different dose effects often seen in studies involving these genes. We define a low exposure-gene effect, when a greater degree of gene environment interaction appears at lower doses of exposure (the interaction follows an inverse dose function), and a converse high exposure-gene effect, when the interaction increases as a function of dose. Using a standard logistic regression model, we define a new term, alpha, that can be determined asa function of exposure dose in order to analyze epidemiological studies for the type of exposure-gene effect. These models are illustrated by the use of hypothetical case-control data as well as examples from the literature.
赋予某些环境致癌物致癌作用增强的遗传易感性的多态性代谢基因，其作用方式符合遗传和环境危险因素之间的2型相互作用。这种相互作用类型，即基因本身对疾病结局没有影响，只是改变与暴露相关的风险，必须与其他类型的基因-环境相互作用区别对待。我们提出了一种方法来分析在涉及这些基因的研究中经常看到的不同剂量效应。我们定义了一种低暴露-基因效应，即当在较低剂量暴露时出现更大程度的基因-环境相互作用（相互作用遵循反剂量函数），以及一种相反的高暴露-基因效应，即当相互作用随剂量增加时。使用标准逻辑回归模型，我们定义了一个新术语α，它可以作为暴露剂量的函数来确定，以便分析流行病学研究中的暴露-基因效应类型。通过使用假设的病例对照数据以及文献中的例子来说明这些模型。
