Comprehensive characterisation of Lynch syndrome and screening strategies: a cohort study of individuals at risk from Latin American genetic registries

Abstract

Systematic screening for Lynch syndrome is non-existent in most Latin American countries. Until regional guidelines are developed and implemented, patients with colorectal cancer in Latin America are being followed up according to international recommendations. The aim of this study was to characterise the current Lynch syndrome screening method in the region, and to explore the prevalence of Lynch syndrome in a large cohort of individuals at risk. We collected clinical, molecular, and genetic data from patients with high-risk colorectal cancer from 24 existing genetic registries and centres from nine countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Puerto Rico, and Uruguay). Information on clinical history, personal or family history of cancer, screening strategy, and molecular and genetic testing was collected by the participating registries through standardised reporting tools. The compiled information was curated and imported into a PostgreSQL database at the Institute of Cancer Research (Oslo, Norway). Data from 1684 patients were included. Universal screening was the most commonly reported screening strategy involved in detection of Lynch syndrome (used to detect Lynch syndrome in 1133 [67·3%] of 1684 patients). The most common method included only immunohistochemistry (336 [29·7%] of 1133), followed by a combination of immunohistochemistry plus microsatellite instability assay (168 [14·8%] of 1133), or immunohistochemistry, BRAFV600E testing, microsatellite instability assay, and MLH1 methylation analysis (133 [11·7%] of 1133). The mutation rate detected with germline mismatch repair sequencing when applying the universal screening strategy was 60 (51%) of 117 versus 87 (47%) of 182 with the clinical criteria. The median age of patients with Lynch syndrome was 40 years (IQR 34-49) and the predominant tumour location was the right colon (109 [43%] of 254), for which the most common stage at diagnosis was stage II (92 [36%] of 254). No multiple tumours were detected in 171 (67%) of 252 patients. Amsterdam criteria were met by 159 (63%) of 254 patients and revised Bethesda guidelines were met by 136 (54%) patients. Our results have implications for the design of future Lynch syndrome screening programmes, but further studies are needed to assess the cost-effectiveness and burden on genetic counselling services with expanded universal testing for Lynch syndrome. Norwegian Cancer Society (contract 194751-2017).