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 breas t and breast-ovarian cancer syndrome families, including those of Ashk enazi 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 so me breast-ovarian cancer families is related to the I1307K mutation, w e evaluated 264 Ashkenazi Jews from 158 families, Most of these indivi duals had either a personal or a family history of breast and/or ovari an cancer, and 19.3% (51 of 264) carried one of the recurrent BRCA1 (1 85delAG or 5382 insC) or BRCA2 (6173delT) mutations, We detected the A PC 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 stud ies, 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 I 1307K mutation, none was diagnosed with colorectal cancer and none had a known first-, second-, or third-degree relative diagnosed with colo n cancer, The results suggest that factors other than the I1307K mutat ion contribute to the increased incidence of colon cancer in Ashkenazi breast-ovarian cancer families, Our results emphasize that only a sub set of Ashkenazi Jewish individuals with a family history of colorecta l cancer should be viewed as candidates for genetic susceptibility tes ting for the I1307K APC mutation.