Drucker L, Stackievitz R, Shpitz B, Yarkoni S
Laboratory of Oncogenetics, Sapir Medical Center, Tel Aviv University, Kfar Sava, Israel.
Anticancer Res. 2000 Jan-Feb;20(1B):559-61.
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.
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.
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.
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.
BRCA基因的突变与结直肠癌（CRC）发病率升高相关。虽然20%的CRC患者有结肠恶性肿瘤家族史，但只有5%的患者的遗传背景是明确的。因此，这些患者中的大多数缺乏任何已知的遗传标志物。我们的目的是探讨BRCA突变作为CRC患者遗传筛查和咨询中此类标志物的相关性。
对136例连续的以色列犹太散发性CRC患者进行BRCA“阿什肯纳兹突变”筛查：185delAG、5382insC和6174delT。采用聚合酶链反应（PCR）、限制性分析、单链构象多态性（SSCP）和Pronto BRCA试剂盒评估携带状态。
我们在87例接受检测的阿什肯纳兹患者中发现1例185delAG携带者和2例6174delT携带者，共3例阿什肯纳兹携带者，占3.5%。在接受调查的阿拉伯人和非阿什肯纳兹犹太人中未发现携带者。
我们的初步结果显示阿什肯纳兹CRC患者中BRCA“阿什肯纳兹突变”的发生率升高，提示它们参与CRC致癌过程。开展更广泛的研究将确定这些突变作为CRC遗传标志物的作用。
