Conway K, Edmiston S, Fried D B, Hulka B S, Garrett P A, Liu E T
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill 27599, USA.
Breast Cancer Res Treat. 1995 Jul;35(1):97-104. doi: 10.1007/BF00694750.
Over the last several years, evidence has accumulated to support the idea that rare Ha-ras polymorphisms are associated with inherited susceptibility to certain human cancers. A recent epidemiologic study conducted at our institution found a significant association specifically with breast cancer, although the mechanism underlying this relationship remains unclear. We have proposed that rare Ha-ras alleles are markers of a genomic instability that predisposes to breast cancer. To address this hypothesis, we are investigating the relationship between the presence of rare alleles and another form of instability, gene amplification, and are developing new methodologies both to improve VNTR allele length detection and to characterize the internal repeat sequence variations of the various alleles. These studies should enable us to more clearly define the role of this region in cancer development by delineating VNTR structure and function and the mechanisms of rare allele generation. Ultimately, we hope to identify VNTR characteristics that will permit more accurate cancer risk assessment.
在过去几年里，已有越来越多的证据支持这样一种观点，即罕见的Ha-ras基因多态性与某些人类癌症的遗传易感性相关。我们机构最近进行的一项流行病学研究发现，这种相关性尤其体现在乳腺癌上，尽管这种关系背后的机制仍不清楚。我们提出，罕见的Ha-ras等位基因是一种基因组不稳定性的标志物，这种不稳定性易引发乳腺癌。为了验证这一假设，我们正在研究罕见等位基因的存在与另一种不稳定性形式——基因扩增之间的关系，并正在开发新的方法，以改进VNTR等位基因长度检测，并对各种等位基因的内部重复序列变异进行表征。这些研究应能使我们通过描绘VNTR的结构和功能以及罕见等位基因产生的机制，更清楚地界定该区域在癌症发展中的作用。最终，我们希望识别出能够实现更准确癌症风险评估的VNTR特征。
