Lynch Syndrome and Ethnicity: Disparities in Prevalence, Affected Genes, Cancer Spectrum and Screening

ABSTRACT

Lynch Syndrome (LS) patients have a significantly increased risk for colorectal cancer (CRC), as well as extracolonic malignancies. This review aims to summarize published data on the prevalence of LS, affected genes, the cancer spectrum, and universal screening across different populations. We conducted a narrative review of English‐language studies published in scientific databases addressing these key aspects of LS. The reported prevalence of LS among unselected CRC patients ranges from 0.7% to 4%, with a higher rate observed in selected high‐risk patients. The overall prevalence of LS was reported to be 2.2% in a large meta‐analysis. Among patients with endometrial cancer, the prevalence has been reported to reach 5.9% in Canadian patients. Notably, the prevalences of LS in both CRC and endometrial cancer show large variations across different geographic regions and ethnic groups. In most populations, the genes most frequently affected are path_MLH1 and path_MSH2. However, in certain regions, path_PMS2 mutations appear to be more common. This pattern has been observed in small cohorts from Arab countries, as well as in isolated studies from the United Kingdom and the United States. In addition, the cumulative cancer risk for CRC, endometrial, ovarian, and urothelial cancers varies widely in different populations. Studies involving unselected patients are more commonly conducted in European countries and the United States (US). In contrast, studies from other regions primarily included selected high‐risk patients. In conclusion, the geographic and ethnic variations underscore the need for population‐specific data and tailored screening strategies, with individualized genetic analysis and surveillance protocols.