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.
World journal of urology. 2023 Mar 24 [Epub ahead of print]
Clara Cerrato, Savio Domenico Pandolfo, Riccardo Autorino, Andrea Panunzio, Alessandro Tafuri, Antonio Benito Porcaro, Alessandro Veccia, Vincenzo De Marco, Maria Angela Cerruto, Alessandro Antonelli, Ithaar H Derweesh, Maria Carmen Mir Maresma
Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Urology Unit, "Federico II University", Naples, Italy., Department of Urology, Rush University Medical Center, Chicago, IL, USA., Department of Urology, Vito Fazzi" Hospital, Lecce, Italy., Department of Urology, UC San Diego School of Medicine, La Jolla, USA., Department of Urology, Hospital Universitario La Ribera, Valencia, Spain. .