Parametric and nonparametric methods for understanding the relationship between carcinogen-induced DNA adduct levels in distal and proximal regions of the colon
Parametric and nonparametric methods for understanding the relationship between carcinogen-induced DNA adduct levels in distal and proximal regions of the colon
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DOI：
10.1198/016214501753208528
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发表时间：
2001-09-01
影响因子：
3.7
通讯作者：
Carroll, RJ
中科院分区：
文献类型：
--
作者：
Morris, JS;Wang, NY;Carroll, RJ
研究结肠癌病因学的一个重要问题是了解在用致癌物和不同类型的饮食治疗后，结肠远端和近端部分的结肠隐窝内细胞中的DNA加合物水平（广义地说，DNA损伤）之间的关系。特别是，重要的是要了解在远端区域隐窝的特定位置具有升高的加合物水平的大鼠是否在近端区域隐窝的相同位置也具有升高的水平，以及这种关系是否取决于饮食。我们把这个问题作为估计两个响应的相关函数作为协变量的函数的研究，其中两个响应是在相同的实验单位，但不是相同的二次抽样单位测量。参数和非参数方法的开发和应用到一个正在进行的研究的数据集，导致潜在的重要和令人惊讶的生物学结果。理论计算表明，基于非参数回归的非参数方法实际上应该具有几乎相同的统计特性，就像非参数估计的函数是已知的一样。本文中使用的方法可以应用于其他设置，当研究的目标是将两个连续重复测量响应的相关性建模为协变量的函数时，而感兴趣的两个响应可以在相同的实验单元上测量，但不能在相同的子采样单元上测量。在我们的示例中，两个响应在结肠的两个不同区域中测量。
An important problem in studying the etiology of colon cancer is understanding the relationship between DNA adduct levels (broadly, DNA damage) in cells within colonic crypts in distal and proximal parts of the colon, following treatment with a carcinogen and different types of diet. In particular, it is important to understand whether rats who have elevated adduct levels in particular positions in distal region crypts also have elevated levels in the same positions of the crypts in proximal regions, and whether this relationship depends on diet. We cast this problem as estimating the correlation function of two responses as a function of a covariate for studies where both responses are measured on the same experimental units but not the same subsampling units. Parametric and nonparametric methods are developed and applied to a dataset from an ongoing study, leading to potentially important and surprising biological results. Theoretical calculations suggest that the nonparametric method, based on nonparametric regression, should in fact have statistical properties nearly the same as if the functions nonparametrically estimated were known. The methodology used in this article can be applied to other settings when the goal of the study is to model the correlation of two continuous repeated measurement responses as a function of a covariate, whereas the two responses of interest can be measured on the same experimental units but not on the same subsampling units, In our example, the two responses were measured in two different regions of the colon.