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抗击结直肠癌:德系犹太人与西班牙系犹太人及巴勒斯坦人之间的分子流行病学差异

Fighting colorectal cancer: molecular epidemiology differences among Ashkenazi and Sephardic Jews and Palestinians.

作者信息

Darwish H, Trejo I E, Shapira I, Oweineh S, Sughayer M, Baron L, Aljadeff E, Silbermann M, Sweidan W, Zilberg D, Halpern Z, Hibshoosh H, Arber N

机构信息

Department of Biochemistry, Al Quds University, Palestinian Authority, Israel.

出版信息

Ann Oncol. 2002 Sep;13(9):1497-501. doi: 10.1093/annonc/mdf230.

Abstract

BACKGROUND

To evaluate and compare differences in the molecular genetics among high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk (Palestinians) groups for colorectal cancer who live in the same geographical region.

PATIENTS AND METHODS

The 1995-1996 records from the Tel Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified patients with colorectal cancer. There were 25 patients from each ethnic group. Epidemiological data were obtained from interviews with the patients and from their hospital charts. The levels of cyclin D1, beta-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. The main outcome measures were the association between gene expression and colorectal incidence in the different ethnic groups.

RESULTS

Ashkenazi Jews have the highest rate of colorectal cancer, and are diagnosed at an early stage compared with Palestinians (72% and 33% of the cases are in Dukes' A and B, respectively), and, hence, this may explain the better 5-year survival rate among this group. Sephardic Jews are diagnosed at a more advanced stage, the tumors are poorly differentiated and they lack p27. Palestinians have significantly higher cyclin D1 levels. There was a statistically significant inverse correlation between the expression of beta-catenine and cyclin D1, as well as p53 and p27 (P <0.05).

CONCLUSIONS

Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially explained by their better molecular biology profile.

摘要

背景

评估并比较生活在同一地理区域的结直肠癌高风险组(阿什肯纳兹犹太人)、中风险组(西班牙裔犹太人)和低风险组(巴勒斯坦人)之间的分子遗传学差异。

患者与方法

从特拉维夫医疗中心和穆卡塞德医院(东耶路撒冷)1995 - 1996年的记录中随机选取结直肠癌患者。每个种族组有25例患者。通过对患者的访谈及其医院病历获取流行病学数据。采用免疫组织化学法测定细胞周期蛋白D1、β-连环蛋白、p27、p53、Ki-67和Her-2/neu蛋白的水平。主要观察指标为不同种族组中基因表达与结直肠癌发病率之间的关联。

结果

阿什肯纳兹犹太人的结直肠癌发病率最高,与巴勒斯坦人相比,他们在早期被诊断出来(分别有72%和33%的病例处于杜克A期和B期),因此,这可能解释了该组较好的5年生存率。西班牙裔犹太人被诊断时处于更晚期阶段,肿瘤分化差且缺乏p27。巴勒斯坦人的细胞周期蛋白D1水平显著更高。β-连环蛋白与细胞周期蛋白D1以及p53与p27的表达之间存在统计学上显著的负相关(P <0.05)。

结论

细胞周期蛋白D1、p53、Ki-67、β-连环蛋白和Her-2/neu表达增加以及p27表达降低可能是这三个患结直肠癌种族组中的重要事件。阿什肯纳兹犹太人较低的死亡率可能部分归因于其较好的分子生物学特征。

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