The I1307K APC mutation does not predispose to colorectal cancer in Jewish Ashkenazi breast and breast-ovarian cancer kindreds

An increased incidence of colorectal canter 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, 11307K, 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 (6173delT) 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.