Woodage T, King S M, Wacholder S, Hartge P, Struewing J P, McAdams M, Laken S J, Tucker M A, Brody L C
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1998 Sep;20(1):62-5. doi: 10.1038/1722.
Mutations in APC are classically associated with familial adenomatous polyposis (FAP), a highly penetrant autosomal dominant disorder characterized by multiple intestinal polyps and, without surgical intervention, the development of colorectal cancer (CRC). APC is a tumour-suppressor gene, and somatic loss occurs in tumours. The germline T-to-A transversion responsible for the APC I1307K allele converts the wild-type sequence to a homopolymer tract (A8) that is genetically unstable and prone to somatic mutation. The I1307K allele was found in 6.1% of unselected Ashkenazi Jews and higher proportions of Ashkenazim with family or personal histories of CRC (ref. 2). To evaluate the role of I1307K in cancer, we genotyped 5,081 Ashkenazi volunteers in a community survey. Risk of developing colorectal, breast and other cancers were compared between genotyped I1307K carriers and non-carriers and their first-degree relatives.
APC基因的突变通常与家族性腺瘤性息肉病（FAP）相关，这是一种高度显性的常染色体显性疾病，其特征为多个肠道息肉，若不进行手术干预，会发展为结直肠癌（CRC）。APC是一种肿瘤抑制基因，在肿瘤中会发生体细胞缺失。导致APC I1307K等位基因的种系T到A颠换将野生型序列转化为一个同聚物序列（A8），该序列在基因上不稳定，易于发生体细胞突变。在6.1%的未选择的德系犹太人中发现了I1307K等位基因，在有结直肠癌家族史或个人史的德系犹太人中该等位基因比例更高（参考文献2）。为了评估I1307K在癌症中的作用，我们在一项社区调查中对5081名德系犹太志愿者进行了基因分型。比较了基因分型的I1307K携带者和非携带者及其一级亲属患结直肠癌、乳腺癌和其他癌症的风险。
