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[林奇综合征的性别特异性方面——最新进展]

[Gender-specific aspects of Lynch syndrome--an update].

作者信息

Schneider R, Fürst A, Möslein G

机构信息

Department of Hereditary Tumor Syndroms; Surgical Center, HELIOS Clinic, University Witten/Herdecke; Wuppertal, Germany.

Department of Surgery, Caritas-Hospital St. Josef, Regensburg, Germany.

出版信息

Z Gastroenterol. 2015 Aug;53(8):789-93. doi: 10.1055/s-0035-1553343. Epub 2015 Aug 18.

Abstract

Approximately 3-5% of all colorectal cancers are based on a hereditary predisposition, of which Lynch syndrome is by far the most frequent hereditary cancer syndrome. Beside colorectal cancer Lynch-Syndrome is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. Genetically Lynch syndrome is caused by a germline mutation in one of the so-called mismatch-repair-genes. Based on several epidemiological studies, increasingly differences in the penetrance of the different cancers occurring are associated with the affected gene and also gender of the patient have been reported. The lifetime risk of colorectal cancer for males with Lynch syndrome generally is significantly higher and the age of first manifestation significantly earlier compared to females. The difference is especially notable in men with a MSH6-mutation. Moreover, the lifetime risk for gastric, bladder, and urothelial cancer is much higher in males. Women with an MSH6 mutation have a much higher risk for endometrial (and ovarian) cancer than for colorectal cancer. In patients with Muir Torre syndrome again males are predominantly affected and almost all affected have a mutation in MSH2 rather than in any other MMR gene. This review is an update of the literature analyzing gen and gender specific aspects of Lynch syndrome. To date these associations are based on retrospective studies, that require confirmation in a prospective setting with large patient numbers in order to identify validated, individualized gene and gender screening recommendations in the future. Especially in a syndrome with multiple potential cancer targets, an intense yearly program comprising several invasive procedures has a negative effect on patient compliance.

摘要

所有结直肠癌中约3-5%是由遗传易感性引起的,其中林奇综合征是迄今为止最常见的遗传性癌症综合征。除了结直肠癌,林奇综合征是子宫内膜癌最常见的遗传性易感病因,还与胃癌、卵巢癌、泌尿系统癌症以及其他几种癌症有关。从基因角度来看,林奇综合征是由所谓错配修复基因之一的种系突变引起的。基于多项流行病学研究,已报告不同癌症发生的外显率差异越来越多地与受影响的基因以及患者性别相关。林奇综合征男性患结直肠癌的终生风险通常明显更高,首次发病年龄也明显早于女性。这种差异在携带MSH6突变的男性中尤为显著。此外,男性患胃癌、膀胱癌和尿路上皮癌的终生风险要高得多。携带MSH6突变的女性患子宫内膜癌(和卵巢癌)的风险远高于患结直肠癌的风险。在穆尔-托里综合征患者中,同样男性受影响为主,几乎所有受影响者都有MSH2突变而非其他任何错配修复基因的突变。本综述是对分析林奇综合征基因和性别特异性方面的文献的更新。迄今为止,这些关联基于回顾性研究,需要在前瞻性研究中纳入大量患者进行验证,以便未来确定经过验证的、个性化的基因和性别筛查建议。特别是在一种有多种潜在癌症靶点的综合征中,每年密集进行包括多种侵入性检查的项目会对患者依从性产生负面影响。

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