The rate of the 6174delT founder Jewish mutation in BRCA2 in patients withnon-colonic gastrointestinal tract tumours in Israel

Inherited predisposition occurs in 5-10% of all gastrointestinal (GI) cance r patients, but with the exception of colorectal cancer (CRC), the genes in volved in conferring genetic susceptibility remain largely unknown. Indirec t evidence indicates that germline mutations in BRCA2 might be associated w ith an increased risk for various GI malignancies. A single mutation (6174d elT) occurs in the BRCA2 gene in high-risk breast ovarian cancer families o f Jewish Ashkenazi origin, in about 1% of the general Ashkenazi population, and rarely in non-Ashkenazi Jews. In order to assess the contribution of t his germline mutation to non-CRC GI cancer in Jewish Israeli patients, we t ested 70 unselected, consecutive Jewish Ashkenazi patients with gastrointes tinal malignancies for this mutation by PCR amplification and modified rest riction enzyme digests. Patients' age range was 38-90 years (mean 65.8+/-11 .8 years). The most common malignancies were gastric cancer (n = 35) and ex ocrine pancreatic cancer (n = 23). Overall, 6 mutation carriers were detect ed: 3/23 (13%) of the patients with pancreatic cancer, 2/35 (5.7%) of patie nts with gastric cancer and 1/4 (25%) of patients with bile duct cancer. Th e 8.6% mutation carrier rate among patients is a rate significantly higher than that of the general Ashkenazi population (1.16% P = 0.0002). We conclu de that the rate of the predominant Jewish BRCA2 mutation in patients with gastric and pancreatic cancer significantly differ from that of the general population of the same ethnic origin. Thus, BRCA2 mutations probably contr ibute to gastrointestinal tumorigenesis other then colon cancer, and the su rveillance scheme for mutation carriers should incorporate this information . (C) 2001 Cancer Research Campaign.