Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Urology Unit, "Federico II University", Naples, Italy.
World J Urol. 2023 Jul;41(7):1741-1749. doi: 10.1007/s00345-023-04344-9. Epub 2023 Mar 24.
Lynch syndrome (LS) is an autosomal dominant genetic syndrome resulting in a wide spectrum of malignancies caused by germline mutations in mismatch repair genes (MMR). Gene mutations have different effects and penetrance between the two genders. The aim of this review is to offer a gender-specific evidence-based clinical guide on diagnosis, screening, surveillance, and counselling of UTUC patients with LS.
Using MEDLINE, a non-systematic review was performed including articles between 2004 and 2022. English language original articles, reviews, and editorials were selected based on their clinical relevance.
Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Up to 21% of new UTUC cases may have unrecognized LS as the underlying cause. LS-UTUC does not have a clear gender prevalence, even if it seems to slightly prefer the male gender. The MSH6 variant is significantly associated with female gender (p < 0.001) and with gynecological malignancies. Female MSH2 and MLH1 carriers have higher rates for endometrial and ovarian cancer with respect to the general population, while male MSH2 and MLH1 carriers have, respectively, higher rate of prostate cancer and upper GI tract, or biliary or pancreatic cancers. Conflicting evidence remains on the association of testicular cancer with LS.
LS is a polyhedric disease, having a great impact on patients and their families that requires a multidisciplinary approach. UTUC patients should be systematically screened for LS, and urologists have to be aware that the same MMR mutation may lead to different malignancies according to the patient's gender.
林奇综合征（LS）是一种常染色体显性遗传综合征，由错配修复基因（MMR）的种系突变导致广泛的恶性肿瘤。基因突变在两性之间具有不同的影响和外显率。本综述的目的是为 LS 患者的 UTUC 提供基于性别的循证临床诊断、筛查、监测和咨询指南。
使用 MEDLINE 进行非系统性回顾，纳入 2004 年至 2022 年的文章。根据其临床相关性，选择英语原始文章、综述和社论。
上尿路上皮癌（UTUC）是 LS 中第三大常见恶性肿瘤。多达 21%的新 UTUC 病例可能存在未被识别的 LS 作为潜在病因。LS-UTUC 没有明确的性别流行趋势，即使它似乎略微偏向男性。MSH6 变体与女性性别（p<0.001）和妇科恶性肿瘤显著相关。MSH2 和 MLH1 女性携带者的子宫内膜癌和卵巢癌发病率高于一般人群，而 MSH2 和 MLH1 男性携带者的前列腺癌和上消化道、胆道或胰腺癌症发病率更高。LS 与睾丸癌之间的关联仍存在争议。
LS 是一种多系统疾病，对患者及其家庭有重大影响，需要多学科方法。应系统筛查 LS 患者，泌尿科医生应意识到相同的 MMR 突变可能因患者的性别而导致不同的恶性肿瘤。
