Adenomatous polyposis coli I1307K mutation in Jewish patients with different ethnicity - Prevalence and phenotype

BACKGROUND. A new mutation, I1307K, recently was reported in the adenomatou s polyposis coli (APC) gene. This mutation was found to be predominant in A shkenazi Jews, creating a hypermutable area and predisposing the developmen t of carcinoma. The objective of the current study was to estimate the prev alence of this mutation in several of the ethnic groups that comprise the I sraeli population and to elucidate the clinical features of the mutation ca rriers with colorectal carcinoma (CRC). METHODS. A total of 111 consecutive CRC patients were evaluated and their m edical history and clinical data recorded. The general population (298 Ashk enazim and 189 Yemenites) also was tested for the presence of this mutation . Mutation screening was performed using both the polymerase chain reaction -based amplification refractory mutation system and a commercial APC kit. RESULTS. Of the total of 111 CRC patients, 15 (13.5%) carried the I1307K mu tation and 26 of 487 subjects from the general population (5.3%) carried th e I1307K mutation (P = 0.004). Among the 71 Ashkenazi CRC patients there we re 12 carriers (16.9%) whereas 17 of the 298 Ashkenazi Jewish general popul ation (5.7%) carried the mutation (P = 0.004). Of the 4 CRC patients of Yem enite origin, 3 carried the mutation and 9 carriers were found among 189 su bjects in the general Yemenite population (4.7%) (P = 0.0007). None of the 34 Sepharadic or 2 Arab CRC patients carried the APC I1307K allele. Late ag e at diagnosis (64.6 years +/- 10.0, which is similar to that of the noncar riers), mostly right-sided tumors, and moderate to good differentiation con stituted the phenotype of the mutation carriers. CONCLUSIONS. The authors believe the findings of the current study broaden the known spectrum of ethnic groups in which the APC I1307K mutation is pre valent. The phenotype of the mutation carrier CRC patients does not conform to the expected familial pattern of germline mutations. The phenotype and the differential incidence rate of CRC among APC I1307K carriers of various ethnic groups suggest low penetrance. (C) 2000 American Cancer Society.