Spirio L, Otterud B, Stauffer D, Lynch H, Lynch P, Watson P, Lanspa S, Smyrk T, Cavalieri J, Howard L
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City.
Am J Hum Genet. 1992 Jul;51(1):92-100.
Adenomatous polyps are an intermediate in the pathway to colon carcinoma. An inherited disorder, familial adenomatous polyposis coli (APC), is characterized by hundreds to thousands of adenomatous polyps. A previously reported family had colon cancer associated with a low average but highly heterogenous number of colonic polyps, this phenotype mapped to the APC locus on 5q. Four new families have been ascertained in which the phenotypic pattern was different from classical polyposis but similar to that of the "prototype" kindred reported earlier. By multilocus linkage analysis, the gene responsible for the disease phenotype was mapped, with a high level of confidence, to the APC locus in two of the four families with the attenuated or variant form of polyposis (AAPC); the results for the two remaining kindreds were inconclusive. A combined maximum LOD score of approximately 7.6 at a recombination fraction of 0 was obtained when the results were summed over the four pedigrees with markers closest to the APC locus. The establishment of genetic linkage in such families may point to the APC locus as having a more significant role in inherited predispositions to colorectal cancer than was previously thought.
腺瘤性息肉是结肠癌发展途径中的一个中间阶段。一种遗传性疾病，家族性腺瘤性息肉病（APC），其特征是有数百到数千个腺瘤性息肉。先前报道的一个家族患有结肠癌，其结肠息肉数量平均较少但高度异质，这种表型定位于5号染色体长臂上的APC基因座。现已确定了四个新家族，其表型模式不同于经典息肉病，但与先前报道的“原型”家族相似。通过多位点连锁分析，在四个患有减弱型或变异型息肉病（AAPC）的家族中的两个家族中，导致该疾病表型的基因被高度可信地定位于APC基因座；其余两个家族的结果尚无定论。当对四个与APC基因座最接近的标记的家系结果进行汇总时，在重组率为0时获得了约7.6的组合最大对数优势分数。在此类家族中建立遗传连锁可能表明，APC基因座在遗传性结直肠癌易感性中所起的作用比之前认为的更为重要。
