Adriana Della Valle¹, Benedito Mauro Rossi², Edenir Inêz Palmero³, Marina Antelo⁴, Carlos Alberto Vaccaro⁵, Francisco López-Kostner⁶, Karin Alvarez⁶, Marcia Cruz-Correa⁷, Luisina Inés Bruno⁸, Nora Manoukian Forones⁹, Jorge Andres Rugeles Mindiola¹⁰, José Buleje¹¹, Florencia Spirandelli¹², Mabel Bohorquez¹³, Alicia Maria Cock-Rada¹⁴, Yasser Sullcahuaman^15,16, Ivana Nascimento¹⁷, Kiyoko Abe-Sandes¹⁷, Leonardo S Lino-Silva¹⁸, Florencia Petracchi¹⁹, Alejandra Mampel²⁰, Yeni Rodriguez²¹, Norma Teresa Rossi²², Claudio Benavides Yañez²³, Cladelis Rubio²⁴, Tirzah Braz Petta-Lajus²⁵, Elizabeth Lemos Silveira-Lucas²⁶, Geiner Jiménez²⁷, Carlos Mario Muñeton Peña²⁸, Carlos Reyes-Silva²⁹, María de la Luz Ayala-Madrigal³⁰, Julio Sánchez del Monte³¹, Richard Quispe³², Alcides Recalde³³, Florencia Neffa¹, Carlos Sarroca¹, Henrique de Campos Reis Galvão², Mariano Golubicki⁴, Tamara A. Piñero⁵, Pablo G. Kalfayan⁵, Fabiana Alejandra Ferro⁵, Julyann Pérez-Mayoral⁷, Celia Aparecida Marques Pimenta⁹, Sandra Patricia Bello Uyaban¹⁰, Ana Protzel^11,34, Guiliana Chávez^11,34, Milagros Dueñas^11,34, María Luisa Guevara Gil¹¹, Enrique Spirandelli¹², Sergio Chialina¹², Magdalena Echeverry¹³, Luis José Palacios Fuenmayor¹⁴, Mariela Torres^15,16, Thais F. Bonfim Palma¹⁷, Nadia Cambados Héritas¹⁹, Claudia Martin²¹, Alfonso Suárez²⁴, Michael Vallejo²⁴, Ana Rafaela de Souza Timoteo²⁵, Carlos Afanador Ayala²⁸, Gabriela Jaramillo-Koupermann²⁹, Jesús Arturo Hernández-Sandoval³⁰, Angélica Hernandez Guerrero³¹, Constantino Dominguez-Barrera³⁵, Juan Carlos Bazo-Alvarez^36,37,Patrik Wernhoff³⁸, John-Paul Plazzer^39,40, Yesilda Balavarca⁴¹, Eivind Hovig^38,42, Pål Møller^38,43,Mev Dominguez-Valentin³⁸

Authors affiliations

¹Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo. Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay

²Hospital Sirio Libanes, São Paulo, Brazil

³Molecular Oncology Research Center, Barretos Cancer Hospital, Brazil and Barretos School of Health Sciences, Dr. Paulo Prata – FACISB, Barretos, Brazil.

⁴Oncology Section of the Public Hospital of Gastroenterology «Dr. C. B. Udaondo», Buenos Aires, Argentina

⁵Hereditary Cancer Program (PROCANHE), Hospital Italiano, Buenos Aires, Argentina

⁶Laboratorio de Oncología y Genética Molecular, Clínica Los Condes, Santiago, Chile

⁷University of Puerto Rico Medical Sciences Campus Department of Medicine, San Juan, Puerto Rico

⁸Instituto Alexander Fleming, Buenos Aires, Argentina

⁹Gastroenterology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

¹⁰Instituto Medico de Alta Tecnologia Oncomedica, Monteria, Colombia

¹¹Centro de Genética y Biología Molecular, Instituto de Investigación, Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Perú.

¹²Asesoría Genética Oncologica Sanatorio Parque,GO,Rosario Argentina

¹³Grupo de Investigación Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y de Ciencias de Salud, Universidad del Tolima, Ibagué, Colombia

¹⁴Instituto de Cancerología Las Americas, Medellin, Colombia

¹⁵Universidad Peruana de Ciencias Aplicadas, Lima, Peru

¹⁶Instituto de Investigación Genomica, Lima Peru

¹⁷Instituto de Ciências da Saúde/Universidade Federal da Bahia, Salvador, Brazil

¹⁸Departamento de Patologia, Instituto Nacional de Cancerologia, Mexico City, Mexico

¹⁹Centro de Educacion Medica e investigaciones Clinicas (CEMIC), Buenos Aires, Argentina

²⁰Instituto de Genética, Area Genética UNde Cuyo, COIR Centro Oncológico de Integración Regional, Mendoza, Argentina

²¹Clinica del Country, Bogota, Colombia

²²Hospital Privado Universitario de Cordoba, Cordoba, Argentina

²³Hospital Regional de Concepción, Concepcion, Chile

²⁴Hospital de San José, Bogota, Colombia

²⁵Liga Norte-Riograndense contra o Cancer, Natal, Brazil

²⁶Consultorio Genetica Clinica, Porto Alegre, Brazil

²⁷Hospital Dr. Rafael Ángel Calderón Guardia, San José, Costa Rica

²⁸Unidad de Genética Médica, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia

²⁹Hospital de Especialidades Eugenio Espejo, Subproceso de Anatomía Patológica, Área de Genética Clínica, Quito, Ecuador

³⁰Instituto de Genética Humana «Dr. Enrique Corona Rivera» y Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, Mexico

³¹Departamento de Gastroenterologia, Instituto Nacional de Cancerologia de México, México City, México

³²Laboratorio de Genética Molecular del Instituto de Servicios de Laboratorio de Diagnóstico e Investigación en Salud (SELADIS), La Paz, Bolivia

³³Facultad de Ciencias Medicas Médicas, Universidad Nacional de Asunción, Asuncion, Paraguay

³⁴Hospital Nacional Edgardo Rebagliati Martins, EsSalud, Lima,Perú

³⁵Facultad de Enfermería, Universidad Particular Ricardo Palma, Lima, Peru

³⁶Research Department of Primary Care and Population Health, University College London, UK

³⁷Instituto de Investigación, Universidad Católica los Ángeles de Chimbote (ULADECH-Católica), Chimbote, Perú

³⁸Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

³⁹Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia
⁴⁰Department of Medicine, Melbourne University, Melbourne, Australia

⁴¹Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany

⁴²Institute for Informatics, University of Oslo

⁴³Department of Human Medicine, Universität Witten/Herdecke, Germany

Correspondence:

Mev Dominguez-Valentin, Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital. Email Mev.Dominguez.Valentin@rr-research.no. Phone: +4740381634

Abstract

Aim. To assess the current genetics practice to manage Lynch syndrome (LS) patients across the Latin American countries, and collaborative research initiatives.

Methods. We conducted a Latin American LS survey, covering questions about institutional structure, clinical and genetic information, management of patients and research initiatives. The survey was sent out to 52 centers/registers assessing and treating LS patients, which comprise a total of 12 countries in the region.

Results. Overall, 33 centers completed the survey, of which, the oldest LS register was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Juan (Puerto Rico). Three out of the 33 centers reported to be only research based or is no longer active. Systematic microsatellite instability testing has been described in 4/30 (13.3%), while immunohistochemistry (IHC) analysis in 9/30 (30%), and both analyses were undertaken in 5/30 (16.7%). In total, 87% (26/30) of the participating centers/registers belonging to 9 countries are performing genetic testing mainly using a panel of LS cancer associated gene testing. Overall, 1.352 suspected families were sequenced and Class 4 or 5 mismatch repair (MMR) gene variants were identified in 34% (459 families), with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p=0.023), while path_MSH2 in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p<0.001), and path_EPCAM in 0.3% of females and 2% of males. Regarding national or international research collaborations, 55% (18/33) reported having collaborations within Latin America, Europe, USA and Australia. Nonetheless, the membership at national or international scientific societies is low, e.g. GETH (24%), InSIGHT (18%), CGA (12%) and EHTG (6%). Importantly, 65% (17/26) of the informing centers/registers, did not report MMR variants to national or international databases, while 58% (15/26) described to have access to an international expert opinion (mainly European).

Conclusion. In Latin America, 9 out of 12 (75%) participating countries had implemented health care for LS. LS screening is inconsistently applied within Latin America healthcare systems as the structure of the health care differed between the countries. Path_MMR variants were described in 459/1352 (34%) families tested, most of which in the MLH1 or MSH2 genes followed by PMS2. Path_MLH1 variant showed predominance in male while path_MSH6 variant in female carriers. The countries with well-functioning system they may serve as models for health care to other forms of inherited cancers.