Mapping the Prevalence of Lynch Syndrome in the Ceará-Northeast of Brazil

Lynch syndrome (LS) is an autosomal dominant hereditary disorder that increases the risk of various cancers, especially colorectal (CRC) and endometrial cancer (EC). It results from pathogenic variants in mismatch repair (MMR) genes-primarily MLH1, MSH2, MSH6, and PMS2. Population-specific variant frequencies emphasize the need for localized genetic studies. Methods This study investigated LS prevalence in Ceará, Northeast Brazil, analyzing 150 patients: 130 with CRC, 13 with endometrial cancer, and 7 with other tumors but a family history of LS-associated cancers. Researchers used next-generation sequencing (NGS) to examine 131 genes linked to hereditary cancer syndromes. Variants were classified as Lynch-syndrome associated (MMR genes) or non-Lynch-associated (non-MMR genes). Detection rates varied from 1.18 to 5.07 per 100,000 people; pathogenic variant prevalence ranged from 0 to 1.96 per 100,000 across microregions. Overall, the prevalence of MMR variants was 0.56 per 100,000, and 0.34 for non-MMR variants. MSH2 showed the highest number of pathogenic or likely pathogenic variants, followed by MSH6, PMS2, and MLH1. The study found a particular geographic distribution of LS-related variants. One novel MSH6 variant and two unreported non-Lynch variants (APC and SMAD4) were identified. Conclusions These findings highlight three novel variants in MSH6, APC, and SMAD4, and indicate that Ceará has a higher diversity and a unique spectrum of variants. This reinforces the importance of regional genetic screening and suggests the need to expand testing access, especially in high-risk areas, to improve the early detection and prevention of hereditary cancers in Northeast Brazil.