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微卫星标记物在预测溃疡性结肠炎发育异常中的应用。

Use of a microsatellite marker in predicting dysplasia in ulcerative colitis.

作者信息

Hunt L E, Eichenberger M R, Petras R, Galandiuk S

机构信息

Price Institute of Surgical Research, Department of Surgery, University of Louisville, KY 40292, USA.

出版信息

Arch Surg. 2000 May;135(5):582-5. doi: 10.1001/archsurg.135.5.582.

Abstract

BACKGROUND

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer. The current screening protocol involves an annual colonoscopy and biopsy after the patient has had the disease for 8 years. This, however, does not prevent the development of colorectal cancer.

HYPOTHESIS

A microsatellite marker for IBD1 may identify individuals who are at greater risk of developing dysplasia and therefore colorectal cancer.

DESIGN

Case-control study.

SETTING

Single surgical practice.

PATIENTS AND METHODS

DNA was extracted from peripheral leukocytes of 152 patients: 22 with UC and dysplasia; 48 with UC and no dysplasia; 24 with colorectal cancer; and 58 with noninflammatory bowel disease, nonmalignant gastrointestinal tract disease who were used as control patients. A microsatellite marker for IBD1 (D16S541) was amplified by polymerase chain reaction. Genotypes were identified using autoradiography.

RESULTS

Six alleles and 15 genotypes were identified for marker D 16S541. Genotype CC was found in 33% (8/24) of cancer patients but only 12% (7/58) of controls (chi2 = 5.5; P = .02). Thirty-two percent (7/22) of patients with dysplastic UC also had this genotype, whereas only 8% (4/ 48) of patients with nondysplastic UC had the genotype (chi2 = 4.6; P = .03; vs controls: chi2 = 3.1; P = .08).

CONCLUSIONS

This microsatellite marker for IBD1, when combined with other markers, has the potential to be used as a screening tool for colorectal cancer and dysplasia in patients with UC. Such a marker would be of particular use in improving the sensitivity and specificity of the current screening protocol for dysplasia and colorectal cancer for patients with UC.

摘要

背景

溃疡性结肠炎(UC)患者患结直肠癌的风险增加。目前的筛查方案是在患者患病8年后每年进行结肠镜检查和活检。然而,这并不能预防结直肠癌的发生。

假说

IBD1的微卫星标记物可能识别出发生发育异常进而患结直肠癌风险更高的个体。

设计

病例对照研究。

地点

单一外科诊所。

患者与方法

从152例患者的外周血白细胞中提取DNA:22例患有UC并伴有发育异常;48例患有UC但无发育异常;24例患有结直肠癌;58例患有非炎症性肠病、非恶性胃肠道疾病的患者作为对照。通过聚合酶链反应扩增IBD1(D16S541)的微卫星标记物。使用放射自显影鉴定基因型。

结果

标记物D16S541鉴定出6个等位基因和15种基因型。基因型CC在33%(8/​24)的癌症患者中发现,但在对照组中仅为12%(7/​58)(χ2 = 5.5;P = 0.02)。32%(7/​22)发育异常的UC患者也有这种基因型,而无发育异常的UC患者中只有8%(4/​48)有该基因型(χ2 = 4.6;P = 0.03;与对照组相比:χ2 = 3.1;P = 0.08)。

结论

这种IBD1的微卫星标记物与其他标记物结合时,有可能用作UC患者结直肠癌和发育异常的筛查工具。这样一种标记物对于提高目前UC患者发育异常和结直肠癌筛查方案的敏感性和特异性将特别有用。

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