N92: Chilean Hereditary Colorectal Cancer Registry: Experience from Clinica Las Condes

K. Alvarez, F. López-Köstner

Unidad de Coloproctología, Clínica Las Condes, Santiago, Chile

Aim: Considering the lack of genetic studies in our country and the benefits resulting from being able to differentiate between carrier and non-carrier individuals, in 2003 we applied for grant funds offered by the Chilean government (FONDECYT). During 2004-2006, this support enabled us to implement the MSI and IHC analyses in tumors, as well as the detection of point mutations in APC, MLH1 and MSH2 genes. In 2009, with the aim of increasing the mutation detection rate, genetic studies were supplemented with deletion/duplication analysis by MLPA for APC, MLH1, MSH2 and EPCAM genes, and the identification of point mutations in MUTYH, MSH6, PMS2, STK11, PTEN, SMAD4 and BMPR1A genes. Today, we have broadened the genetic studies into gene panels (Invitae, USA), mainly in those patients whose tumor studies do not allow us to define a candidate gene or when the definition of the hereditary syndrome becomes quite difficult.

Methods: Patients are referred to the program of hereditary colorectal cancer for evaluation. Those that meet criteria are included into the registry, which generally contained data on family history, clinical information, age at onset and results of DNA testing or tumor screening. Written informed consent was obtained from all patients during genetic counseling sessions. In our registry, we have an overall record of 221 suspected families (with 533 registered individuals), 107 are Lynch syndrome suspected families, 98 familial adenomatous polyposis, 11 Peutz-Jeghgers syndrome, 2 juvenil polyposis, 1 Cowden syndrome and 2 hyperplastic polyposis. In total, 88 families present a mutation or variant of uncertain significant in APC (41), MUTYH (3), MLH1 (21), MSH2 (7), MSH6 (1), PMS2 (3), EPCAM (2), STK11 (8), PTEN (1) and SMAD4 (1) genes. In those families with pathogenic or likely pathogenic mutations, we have studied 386 relatives, of which, 223 are carriers and 163 are no carriers. All families have received clinical recommendations based on the National Comprehensive Cancer Network (NCCN) guidelines. Interestingly, 25 mutations have not yet been described in other studies, clearly demonstrating the relevance of evaluating different racial/ethnic populations like ours, which include an admixture of Amerindian and European -mainly Spanish – populations.

Conclusion: Our work shows the success to integrate multidisciplinary professionals as coloproctologists, PhD in biological sciences (genetic counselor), nurses, medical doctors from various disciplines, and the constant support of a psycho-oncologist. We would like to highlight our last challenge, a pioneering initiative in Latin America, which consisted in the creation of a Course of genetic counseling in hereditary cancer aimed for health care professionals belonging to oncology units.

Acknowledgement: We would like to thanks Mev Dominguez-Valentin (Oslo University Hospital, Oslo, Norway), for her unconditional support and her effort.