The APC I1307K allele and cancer risk in a community-based study of Ashkenazi Jews

• Published in: Nature genetics Vol. 20; no. 1; pp. 62 - 65
• Main Authors: Brody, Lawrence C, Woodage, Trevor, King, Sonya M, Wacholder, Sholom, Hartge, Patricia, Struewing, Jeffery P, McAdams, Mary, Laken, Steven J, Tucker, Margaret A
• Format: Journal Article
• Language: English
• Published: 01-09-1998
• ISSN: 1061-4036; 1546-1718
• 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 (A sub(8)) 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. 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.