GENETIC-ANALYSIS OF AN INHERITED PREDISPOSITION TO COLON CANCER IN A FAMILY WITH A VARIABLE NUMBER OF ADENOMATOUS POLYPS
GENETIC-ANALYSIS OF AN INHERITED PREDISPOSITION TO COLON CANCER IN A FAMILY WITH A VARIABLE NUMBER OF ADENOMATOUS POLYPS
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DOI：
10.1056/nejm199003293221306
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发表时间：
1990-03-29
影响因子：
158.5
通讯作者：
WHITE, R
中科院分区：
文献类型：
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作者：
LEPPERT, M;BURT, R;WHITE, R
我们研究了一个有早发性结直肠癌病史的大家族。对51名家庭成员进行直肠乙状结肠镜检查，仅发现2名家族性结肠息肉病，这是结肠癌的强烈倾向，其定义为结肠中存在超过100个息肉。然而，8名家庭成员有2至40个结肠息肉。我们怀疑在这个家族中，结直肠癌是5号染色体上基因突变的结果，该基因是家族性结肠息肉病的原因。为了验证我们的假设，我们获得了81个家庭成员的基因型信息与7个多态性DNA标记先前被证明与家族性结肠息肉病的基因座。多位点数据分析表明，这些标记与该家族中导致结肠息肉或结直肠癌的特定综合征的位点之间存在遗传连锁（lod评分为5.58）。这些发现构成的证据表明，该家族的遗传缺陷是导致家族性结肠息肉病的基因突变。我们的结论是，家族性结肠息肉病基因位点的突变可能是其他更微妙的综合征的原因，涉及遗传易感性结肠腺瘤性息肉和结直肠癌。
We studied a large kindred with a history of colorectal cancer of early onset. Proctosigmoidoscopic examination of 51 family members identified only 2 with familial polyposis coli, which strongly predisposes those who have it to colorectal cancer and which is defined as the presence of more than 100 polyps in the colon. However, eight family members had 2 to 40 colonic polyps. We suspected that in this family, colorectal cancer was the result of a mutation in the gene on chromosome 5 that is responsible for familial polyposis coli. To test our hypothesis, we obtained genotypic information on 81 family members with respect to seven polymorphic DNA markers previously shown to be linked to the locus for familial polyposis coli. Multilocus analysis of the data demonstrated genetic linkage (lod score, 5.58) between these markers and the locus responsible for the defined syndrome of colonic polyps or colorectal cancer in this kindred. These findings constitute evidence that the genetic defect in this family is a mutation in the gene that causes familial polyposis coli. We conclude that mutations at the genetic locus for familial polyposis coli may be the cause of other, more subtile syndromes involving an inherited susceptibility to colonic adenomatous polyps and colorectal cancer.