L Drucker1, R Stackievitz, B Shpitz, S Yarkoni. 1. Laboratory of Oncogenetics, Sapir Medical Center, Tel Aviv University, Kfar Sava, Israel. yark123@inter.net.il
Abstract
BACKGROUND: Mutations in BRCA genes are associated with an elevated incidence of colorectal cancer (CRC). While 20% of CRC patients have a familial history of colonic malignancies, in only 5% is the genetic setting understood. Thus, a majority of these patients lack any known genetic marker. Our aim was to explore the relevance of BRCA mutations to serve as such markers in the genetic screening and counseling of CRC patients. PATIENTS AND METHODS: 136 consecutive Israeli Jewish patients with sporadic CRC were screened for BRCA "Ashkenazi mutations": 185delAG, 5382insC and 6174delT. Carrier status was evaluated employing PCR, restriction analysis, SSCP and a Pronto BRCA kit. RESULTS: We found one 185delAG and two 6174delT carriers, altogether three Ashkenazi carriers out of 87 Ashkenazi patients tested, 3.5%. No carriers were found among the Arabs and non-Ashkenazi Jews surveyed. CONCLUSIONS: Our preliminary results show elevated rates of BRCA "Ashkenazi mutations" in Ashkenazi CRC patients, suggesting their involvement in CRC carcinogenesis. An implementation of a wider study will establish the role of these mutations as genetic markers for CRC.
BACKGROUND: Mutations in BRCA genes are associated with an elevated incidence of colorectal cancer (CRC). While 20% of CRCpatients have a familial history of colonic malignancies, in only 5% is the genetic setting understood. Thus, a majority of these patients lack any known genetic marker. Our aim was to explore the relevance of BRCA mutations to serve as such markers in the genetic screening and counseling of CRCpatients. PATIENTS AND METHODS: 136 consecutive Israeli Jewish patients with sporadic CRC were screened for BRCA "Ashkenazi mutations": 185delAG, 5382insC and 6174delT. Carrier status was evaluated employing PCR, restriction analysis, SSCP and a Pronto BRCA kit. RESULTS: We found one 185delAG and two 6174delT carriers, altogether three Ashkenazi carriers out of 87 Ashkenazi patients tested, 3.5%. No carriers were found among the Arabs and non-Ashkenazi Jews surveyed. CONCLUSIONS: Our preliminary results show elevated rates of BRCA "Ashkenazi mutations" in Ashkenazi CRCpatients, suggesting their involvement in CRC carcinogenesis. An implementation of a wider study will establish the role of these mutations as genetic markers for CRC.
Authors: Ophira M Ginsburg; Charmaine Kim-Sing; William D Foulkes; Parviz Ghadirian; Henry T Lynch; Ping Sun; Steven A Narod Journal: Fam Cancer Date: 2010-12 Impact factor: 2.375