The APCI1307K 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: WOODAGE, T, KING, S. M, WACHOLDER, S, HARTGE, P, STRUEWING, J. P, MCADAMS, M, LAKEN, S. J, TUCKER, M. A, BRODY, L. C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-09-1998
• Subjects: Adenomatous Polyposis Coli Protein; Adult; Aged; Aged, 80 and over; Alleles; Biological and medical sciences; BRCA1 Protein - genetics; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Classical genetics, quantitative genetics, hybrids; Colorectal Neoplasms - ethnology; Colorectal Neoplasms - genetics; Cytoskeletal Proteins - genetics; Europe - ethnology; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Heterozygote; Human; Humans; Jews - genetics; Male; Middle Aged; Mutation; Neoplasms - ethnology; Neoplasms - genetics; Odds Ratio; Europe; Human; Statistical analysis; Family study; Risk factor; Loss of heterozygosity; Tumor; Mutation; Genetic association; Jew; Ethnic group; Tumor suppressor gene
• ISSN: 1061-4036; 1546-1718

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.