title: The I1307K APC mutation does not predispose to colorectal cancer in Jewish Ashkenazi breast and breast-ovarian cancer kindreds.
abstract: An increased incidence of colorectal cancer has been observed in breast and breast-ovarian cancer syndrome families, including those of Ashkenazi origin. Recently, a germ-line missense mutation in the APC gene, I1307K, was identified that may indirectly cause colorectal cancer in Ashkenazi Jews. To determine whether the excess of colon cancer in some breast-ovarian cancer families is related to the I1307K mutation, we evaluated 264 Ashkenazi Jews from 158 families. Most of these individuals had either a personal or a family history of breast and/or ovarian cancer, and 19.3% (51 of 264) carried one of the recurrent BRCA1 (185delAG or 5382 insC) or BRCA2 (6174delT) mutations. We detected the APC I1307K mutation in 7% (11 of 158) of the Ashkenazi Jewish families and in 4.5% (12 of 264) of the individuals participating in these studies. Of the families studied, 26.6% (42 of 158) had at least one case of colorectal cancer in a first-, second-, or third-degree relative of the proband. Significantly, of the 12 individuals who possessed the I1307K mutation, none was diagnosed with colorectal cancer and none had a known first-, second-, or third-degree relative diagnosed with colon cancer. The results suggest that factors other than the I1307K mutation contribute to the increased incidence of colon cancer in Ashkenazi breast-ovarian cancer families. Our results emphasize that only a subset of Ashkenazi Jewish individuals with a family history of colorectal cancer should be viewed as candidates for genetic susceptibility testing for the I1307K APC mutation.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: L
authors.initials: L
authors.lastname: Petrukhin
authors.forename: J
authors.initials: J
authors.lastname: Dangel
authors.forename: L
authors.initials: L
authors.lastname: Vanderveer
authors.forename: J
authors.initials: J
authors.lastname: Costalas
authors.forename: A
authors.initials: A
authors.lastname: Bellacosa
authors.forename: G
authors.initials: G
authors.lastname: Grana
authors.forename: M
authors.initials: M
authors.lastname: Daly
authors.forename: A K
authors.initials: AK
authors.lastname: Godwin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D004198:Disease Susceptibility; D005192:Family Health; D005260:Female; D017491:Genes, APC; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D010375:Pedigree
chemical_list: D004273:DNA, Neoplasm; D004247:DNA