One of the main focus of the group is about Lynch syndrome (LS), that is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged by our efforts from the Prospective Lynch Syndrome Database (PLSD) which allowed to update the clinical management of LS. Our work has been to conduct an international and multicenter prospective observational study using independent test and validation cohorts of LS. We provided for the first time, larger numbers that allowed to derive more precise risks estimates for cancer in LS categorized by gene and gender.
During the last 4 years, we have been using multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing, to gain information on to which degree other genes may have been causative for cancer in the patients and their relatives, and to be informed on how such genes were deranged to discriminate between normal and disease-causing variants. In addition, we analyzed the impact of a subset of VUS on RNA splicing by the use of minigene assays. Because multiple cancer gene panel testing is rapidly replacing sequential single-gene testing, we need to know how to improve in the way we interpret the findings from panel testing patients in cancer kindreds who have been previously tested for the BRCA1/2, PTEN, TP53 and mismatch repair (MMR) genes without detection of pathogenic variants.
Our group is also interested in unravelling the challenges of implementing the advances in diagnosis of hereditary cancer susceptibility and applying these insights to clinical practice in Latin America. In the Latin American countries, training in human genetics and medical genetics is scarce. Our work has brought knowledge on the genetic background of LS in Latin America and may enable the identification of multiple frequent founder variants, which subsequently may be subjected to testing in the areas where they occur. In addition, we have established national and international collaborations in LS that have been crucial, especially in generating knowledge about MMR gene variant classification and sharing of genetic practices within the region. Collaborative efforts aim to ensure that all Latin Americans have access to genetic services and to bring additional awareness to medical professionals and public health leaders. The importance of this finding was recognized by the scientific community, and also by the general public; it was covered by the media in Latin America and have generated more than 20 scientific publications.
We pursue our interest in the genetic epidemiology of hereditary cancers in low-resource setting in Peru. We have identified a greater proportion of cancer cases than previously described, with a young age of onset and differential profile of the most frequent cancers and analyzed using a gene panel containing 96-cancer associated genes. With the emergence of increasingly effective interventions, it becomes paramount that populations living in resource-limited settings have access to cancer services and participates in genetics and genomic research.