AN ASSOCIATION BETWEEN THE RISK OF CANCER AND MUTATIONS IN THE HRAS1 MINISATELLITE LOCUS
AN ASSOCIATION BETWEEN THE RISK OF CANCER AND MUTATIONS IN THE HRAS1 MINISATELLITE LOCUS
复制标题
DOI：
10.1056/nejm199308193290801
复制
发表时间：
1993-08-19
影响因子：
158.5
通讯作者：
RISCH, N
中科院分区：
文献类型：
--
作者：
KRONTIRIS, TG;DEVLIN, B;RISCH, N
背景原癌基因及其调控序列突变在癌症发病机制中的作用正受到密切关注。小卫星是DNA的不稳定重复序列，存在于整个人类基因组中。高度多态性的HRAS 1小卫星基因座下游的原癌基因H-ras-1由四个常见的祖先等位基因和几十个罕见的等位基因，显然来自突变的祖先。我们以前观察到一种关联的罕见突变等位基因与许多形式的癌症，我们进行了本研究，以进一步追求这一观察。我们进行了一项病例对照研究，分型736 HRAS 1等位基因从癌症患者和652从控制白细胞DNA的Southern印迹。我们还对这项研究和其他22项已发表的研究进行了荟萃分析，估计了当存在一种罕见的HRAS 1等位基因时患癌症（如膀胱癌、乳腺癌或结直肠癌）的相对风险。本病例对照研究（比值比，1.83; 95%置信区间，1.28至2.67; P = 0.002）和本研究结合我们以前的研究（比值比，2.07; 95%置信区间，1.47至2.92; P = 0.002），
Background. The role of mutations in protooncogenes and their regulatory sequences in the pathogenesis of cancer is under close scrutiny. Minisatellites are unstable repetitive sequences of DNA that are present throughout the human genome. The highly polymorphic HRAS1 minisatellite locus just downstream from the protooncogene H-ras-1 consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. We previously observed an association of the rare mutant alleles with many forms of cancer, and we undertook the present study to pursue this observation further.Methods. We conducted a case-control study, typing 736 HRAS1 alleles from patients with cancer and 652 from controls by Southern blotting of leukocyte DNA. We also carried out a meta-analysis of this study and 22 other published studies, estimating the relative risk of cancer (such as bladder, breast, or colorectal cancer) when one of the rare HRAS1 alleles was present.Results. Both the present case-control study (odds ratio, 1.83; 95 percent confidence interval, 1.28 to 2.67; P = 0.002) and the present study combined with our previous study (odds ratio, 2.07; 95 percent confidence interval, 1.47 to 2.92; P