Tritiated Thymidine (φp,φh) Labeling Distribution as a Marker for Hereditary Predisposition to Colon Cancer
Tritiated Thymidine (φp,φh) Labeling Distribution as a Marker for Hereditary Predisposition to Colon Cancer
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氚化胸苷 (φp,φh) 标记分布作为结肠癌遗传倾向的标志物
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
S. Winawer
中科院分区：
文献类型：
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作者：
M. Lipkin;W. Blattner;J. Fraumeni;H. Lynch;E. Deschner;S. Winawer
已经开发出新的分析方法来测量高风险和低风险人群结肠隐窝中[3H]dThd标记的上皮细胞的高度分布模式。标记的细胞根据隐窝高度分为 10 个大小相等的隔室，每个受试者还加上一个腔表面隔室。将易患大肠杆菌息肉病和非息肉病结肠癌的家庭成员与风险较低的受试者进行比较。后者包括来自同一家族的无息肉和无癌症分支的人、正常对照以及来自一般人群的结肠癌患者。当比较所有隐窝高度区室的标记细胞分布时，发现家族性息肉病或家族性结肠癌患者组与低风险受试者之间存在显着差异（p < 0.001）。根据常染色体显性性状的预期，隐窝上部区域（即 40%）标记细胞的占有率分布（即 40%），针对每个群体的比例（φ p ）进行测量，揭示了一种判别水平，该水平将 90% 以上的低风险受试者与大部分患有家族性结肠癌或息肉病的受试者以及接近一半的高危后代区分开来。然而，一般人群中患有结肠癌的受试者的 (φ p , φ h ) 分布更接近于低风险组，尽管一部分患者具有遗传性疾病特征的异常 φ h 值。因此，(φ p , φ h ) 分布似乎是比以前用于区分对结肠癌具有遗传易感性的人群与风险较低的人群更精确的风险度量，并且可用作识别具有高危表型的个体的标记。
New analytical methods have been developed for measurement of the height distribution patterns of [3H]dThd-labeled epithelial cells in colonic crypts of high- and low-risk population groups. Labeled cells were segregated with respect to crypt-height into 10 compartments of equal size, plus a lumenal surface compartment for each subject. Members of families prone to polyposis coli and to non-polyposis colon cancer were compared to subjects at lower risk. The latter included persons from polyp-free and cancer-free branches of the same families, normal controls, and patients with colon cancer from the general population. Significant differences were found between groups of patients with familial polyposis or familial colon cancer and subjects at low risk, when labeled cell distributions were compared over all the crypt height compartments ( p < 0.001). Distributions of the occupancy fractions of labeled cells in the upper region ( i.e. , 40%) of the crypt (φ h ), measured for the fraction of each population (φ p ), revealed a discriminant level that separated over 90% of low-risk subjects from a major fraction of those affected with familial colon cancer or polyposis and from close to one-half of the at-risk progeny as expected for an autosomal dominant trait. However, subjects with colon cancer in the general population had (φ p ,φ h ) distributions closer to the low-risk groups, although a subgroup of patients had abnormal φ h values characteristic of hereditary disease. Thus, the (φ p ,φ h ) distribution appears to be a more precise measure of risk than previously used in discriminating populations with genetic susceptibility to colon cancer from those at lower risk and may be useful as a marker to identify individuals with the at-risk phenotype.