Estimating the prevalence of germline mutations in DNA mismatch repair genes among patients with upper tract urothelial carcinoma: a systematic review and meta-analysis

IF 2.8 3区医学 Q3 ONCOLOGY

Urologic Oncology-seminars and Original Investigations Pub Date : 2026-04-01 Epub Date: 2026-02-10 DOI:10.1016/j.urolonc.2026.110999

Joseph Moryousef MD , Braden Millan MD , Piotr Zareba MD

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引用次数: 0

Abstract

Background

Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1 and PMS2. The objective of this systematic review was to estimate the prevalence of germline mutations in MMR genes among patients with upper tract urothelial carcinoma (UTUC).

Methods

Literature searches were performed using MEDLINE, EMBASE and Web of Science Core Collection. Studies of interest were selected and data were abstracted independently by two reviewers. Prevalence estimates were transformed using the Freeman-Tukey method and pooled using a random effects model. Heterogeneity and publication bias were assessed quantitatively using the I² statistic and Egger’s test, respectively.

Results

Fourteen studies, which included 2,378 patients, were found. Eight of these studies were performed either in China or Japan, with the remainder coming from the United States and Europe. The pooled prevalence of germline mutations in MMR genes was 3.2% (95% confidence interval [95% CI] 2.1%, 4.4%, I²=54%). The prevalence was lower among studies from East Asia than those from North America and Europe (2.4% vs. 4.7%, P=0.087). MSH2 was the most commonly mutated gene and 86% of the patients who tested positive were less than 60 years of age or had a prior cancer diagnosis.

Conclusions

LS prevalence among patients with UTUC is similar to that among patients with colorectal and endometrial cancers, which provides a strong rationale for LS testing in this population. Further research is necessary to determine the optimal diagnostic strategy.

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估计上尿路上皮癌患者DNA错配修复基因种系突变的患病率：一项系统回顾和荟萃分析。

背景：Lynch综合征是由DNA错配修复（MMR）基因MSH2、MSH6、MLH1和PMS2的种系突变引起的遗传性癌症易感性综合征。本系统综述的目的是估计MMR基因在上尿路上皮癌（UTUC）患者中种系突变的患病率。方法：采用MEDLINE、EMBASE和Web of Science Core Collection进行文献检索。选择感兴趣的研究，并由两名审稿人独立提取数据。使用Freeman-Tukey方法对患病率估计进行转换，并使用随机效应模型进行汇总。异质性和发表偏倚分别采用I2统计量和Egger’s检验进行定量评估。结果：共纳入14项研究，包括2378例患者。其中8项研究是在中国或日本进行的，其余的来自美国和欧洲。MMR基因种系突变的总患病率为3.2%（95%置信区间[95% CI] 2.1%, 4.4%, I2=54%）。东亚研究的患病率低于北美和欧洲研究（2.4%比4.7%，P=0.087）。MSH2是最常见的突变基因，86%检测呈阳性的患者年龄小于60岁或有过癌症诊断。结论：UTUC患者的LS患病率与结直肠癌和子宫内膜癌患者相似，这为在该人群中进行LS检测提供了强有力的依据。需要进一步的研究来确定最佳的诊断策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Urologic Oncology-seminars and Original Investigations 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.70%

发文量

297

审稿时长

7.6 weeks

期刊介绍： Urologic Oncology: Seminars and Original Investigations is the official journal of the Society of Urologic Oncology. The journal publishes practical, timely, and relevant clinical and basic science research articles which address any aspect of urologic oncology. Each issue comprises original research, news and topics, survey articles providing short commentaries on other important articles in the urologic oncology literature, and reviews including an in-depth Seminar examining a specific clinical dilemma. The journal periodically publishes supplement issues devoted to areas of current interest to the urologic oncology community. Articles published are of interest to researchers and the clinicians involved in the practice of urologic oncology including urologists, oncologists, and radiologists.