Laken S J, Petersen G M, Gruber S B, Oddoux C, Ostrer H, Giardiello F M, Hamilton S R, Hampel H, Markowitz A, Klimstra D, Jhanwar S, Winawer S, Offit K, Luce M C, Kinzler K W, Vogelstein B
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Nat Genet. 1997 Sep;17(1):79-83. doi: 10.1038/ng0997-79.
Approximately 130,000 cases of colorectal cancer (CRC) are diagnosed in the United States each year, and about 15% of these have a hereditary component. Two well-defined syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), account for up to 5% of the total new cases of CRC. Truncating APC mutations are responsible for FAP, and defective mismatch repair genes cause HNPCC. However, the genes responsible for most of the familial cases are unknown. Here we report a mutation (T to A at APC nucleotide 3920) found in 6% of Ashkenazi Jews and about 28% of Ashkenazim with a family history of CRC. Rather than altering the function of the encoded protein, this mutation creates a small hypermutable region of the gene, indirectly causing cancer predisposition.
在美国，每年约有13万例结直肠癌（CRC）被确诊，其中约15%具有遗传因素。两种明确的综合征，家族性腺瘤性息肉病（FAP）和遗传性非息肉病性结直肠癌（HNPCC），占CRC新发病例总数的5%。截短的APC突变导致FAP，错配修复基因缺陷导致HNPCC。然而，大多数家族性病例的致病基因尚不清楚。在此，我们报告了一种突变（APC核苷酸3920处的T突变为A），在6%的阿什肯纳兹犹太人以及约28%有CRC家族史的阿什肯纳兹人中被发现。该突变并非改变编码蛋白的功能，而是在基因中产生了一个小的高变区，间接导致癌症易感性。
