Genetic analysis of the APC gene regions involved in attenuated APC phenotype in Israeli patients with early onset and familial colorectal cancer

The genetic basis for the majority of early onset or non-syndromic 'familia l' colorectal cancer (CRC) is unknown. Attenuated APC phenotype is characte rized by relatively few colonic polyps, early age at onset of colon cancer compared with the general population, and inactivating germline mutations w ithin specific regions of the APC gene. We hypothesized that germline mutat ions within these APC gene regions, might contribute to early onset or fami lial CRC susceptibility. To test this notion, we analysed 85 Israeli patien ts with either early onset (< 50 years at diagnosis) or familial CRC for ha rbouring mutations within the relevant APC gene regions: exons 1-5, exon 9 and a region within exon 15 (spanning nucleotides c.3900 to c.4034; codons 1294 to 1338) using denaturing gradient gel electrophoresis (DGGE), and all of exon 15 employing protein truncation test (PTT). No inactivating, disea se-associated mutations were detected in any patient. A novel polymorphism in intron 5 was detected in 16 individuals, 8 patients were carriers of the 11307K variant, a mutation prevalent among Jewish individuals with colorec tal cancer, and 4 displayed the E1317Q variant. We conclude that in Israeli individuals with early onset or familial CRC, truncating mutations in the APC gene regions associated with attenuated APC phenotype probably contribu te little to disease pathogenesis. (C) 2001 Cancer Research Campaign.