A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America.

BACKGROUND: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. METHODS: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. RESULTS: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. CONCLUSION: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.

Genetic Characterization in High-Risk Individuals from a Low-Resource City of Peru.

Background: Genetic testing for hereditary cancers is inconsistently applied within the healthcare systems in Latin America. In Peru, the prevalence and spectrum of cancer-predisposing germline variants is thus poorly characterized. Purpose: To determine the spectrum and prevalence of cancer-predisposing germline variants and variants of uncertain significance (VUS) in high-risk individuals located in a Peruvian low-resource setting city. Methods: Individuals presenting clinical criteria for hereditary cancer syndromes or being unaffected with familial history of cancer were included in the study. Samples from a total of 84 individuals were subjected to a high-throughput DNA sequencing assay that targeted a panel of 94 cancer predisposition genes. The pathogenicity of detected germline variants was classified according to the established American College of Medical Genetics and Genomics (ACMG) criteria. All pathogenic variants were validated by cycling temperature capillary electrophoresis. Results: We identified a total of eight pathogenic variants, found in 19 out of 84 individuals (23%). Pathogenic variants were identified in 24% (10/42) of unaffected individuals with family history of cancer and in 21% (9/42) of individuals with a cancer diagnosis. Pathogenic variants were identified in eight genes: RET (3), BRCA1 (3), SBDS (2), SBDS/MLH1 (4), MLH1 (4), TP53 (1), FANCD2 (1), DDB2/FANCG (1). In cancer cases, all colon cancer cases were affected by pathogenic variants in MLH1 and SBDS genes, while 20% (2/10) of the thyroid cancer cases by RET c.1900T>C variants were affected. One patient with endometrial cancer (1/3) had a double heterozygous pathogenic variant in DDB2 and FANCG genes, while one breast cancer patient (1/14) had a pathogenic variant in TP53 gene. Overall, each individual presented at least 17 VUS, totaling 1926 VUS for the full study population. Conclusion: We describe the first genetic characterization in a low-resource setting population where genetic testing is not yet implemented. We identified multiple pathogenic germline variants in clinically actionable predisposition genes, that have an impact on providing an appropriate genetic counselling and clinical management for individuals and their relatives who carry these variants. We also reported a high number of VUS, which may indicate variants specific for this population and may require a determination of their clinical significance.

Challenges to Bringing Personalized Medicine to a Low-Resource Setting in Peru.

We provide an overview of the challenges that low-resource setting cities are facing, including a lack of global implementation of cancer screening programs, accurate data and statistics that may aid the health authorities and guide future public health activities, as well as reorient strategies, interventions and budgets to promote lifestyles that help prevent disease. Current cancer care does not fully reflect ethnic, cultural, environmental and resource differences. Herein, we described a snapshot of the cancer mortality and morbidity from a hospital that cares a rural and low-income population from Peru, called Chimbote (316,966 inhabitants) and showed the limitation of access to oncological care and genetic services. The city is located in the region of Ancash, which is a department of Northern Peru. Of note, we identified a greater proportion of cancer cases than previously described, with a young age of onset and differential profile of the most frequent cancers. With the emergence of increasingly effective interventions, it becomes paramount that populations living in resource-limited settings have access to cancer services and participate in genetics and genomic research.

Update on Hereditary Colorectal Cancer.

In the past two decades, significant advances have been made in our understanding of colorectal (CRC) tumors with DNA mismatch (MMR) repair deficiency. The knowledge from molecular and genetic alterations in a variety of clinical conditions has refined the disease terminology and classification. Hereditary non-polyposis colorectal cancer (HNPCC) encompasses a spectrum of conditions that have significant phenotypic overlapping that makes clinical diagnosis a challenging task. Distinguishing among the HNPCC disorders is clinically important, as the approach to surveillance for patients and their at-risk family members differs according to risks for colonic and extracolonic cancer associated with each syndrome. Prospective and next-generation studies will provide valuable clinical information regarding the natural history of disease that will help differentiate the Lynch syndrome mimics and guide diagnosis and management for heterogeneous conditions currently grouped under the category of familial CRC. The review is intended to present and discuss the molecular nature of various conditions related to MMR deficiency and discusses the tools and strategies that have been used in detecting these conditions.

Menuda Tarea: Hacer gestión en salud en el Perú / Homework: Doing health management in Peru

El editorial Menuda Tarea: Hacer gestión en salud en el Perú , desarrolla un tema relacionado a un componente de la situación de salud que actualmente es muy relevante, pues, motiva a una reflexión e intercambio de posiciones epistemológicas de la comunidad científica de los profesionales de la salud

Actualización en cáncer colorrectal hereditario y su impacto en salud pública / Update on hereditary colorectal cancer and its impact on public health

Resumen Los avances en la investigación clínica, genética y molecular del cáncer colorrectal (CCR) realizados durante los últimos años han permitido su detección temprana, así como su tratamiento oportuno. Sin embargo, uno de los mayores desafíos de esta enfermedad es su naturaleza heterogénea y la participación de diversas vías moleculares en su carcinogénesis. La implementación de las tecnologías ómicas -como la genómica, la proteómica, la transcriptómica y la epigenómica- en la investigación biomédica de pacientes con CCR hereditario ha permitido identificar nuevos genes o polimorfismos de nucléotido único (SNP, por su sigla en inglés) que afectan la expresividad del cáncer. Por otra parte, las herramientas bioinformáticas han contribuido a generar nuevas hipótesis sobre el CCR, orientando el abordaje de estos pacientes hacia una medicina personalizada. Este avance científico y tecnológico tiene un impacto en la salud, tanto a nivel individual como colectivo, por lo que es importante reflexionar sobre la viabilidad de desarrollar estrategias de salud pública para la implementación de un programa integral y genético de prevención y manejo del cáncer en Perú, en especial del CCR hereditario.

Abstract Progress in clinical, genetic and molecular research of colorectal cancer (CRC) in recent years has allowed its early detection and timely and targeted treatment. However, one of the greatest challenges is the heterogeneous nature of CRC and the involvement of various molecular pathways in its carcinogenesis. The implementation of technologies known as omics -such as genomics, proteomics, transcriptomics and epigenomics- in biomedical research on patients with hereditary CRC has allowed the identification of new genes or single nucleotide polymorphisms (SNPs) that affect the expressivity of cancer. Bioinformatics tools have also contributed to generate new hypotheses about CRC, guiding the approach to these patients towards personalized medicine. This scientific and technological progress has an impact on health, both at the individual and the collective level, so it is important to reflect on the feasibility of developing public health strategies for the implementation of a comprehensive and genetic program for the prevention and treatment of cancer in Peru, especially hereditary CRC.

Principios bioéticos en el contexto de la pandemia de COVID-19 / Bioethical principles in the context of the COVID-19 pandemic

RESUMEN El avance de la pandemia de COVID 19 a escala mundial ha desencadenado una crisis en los sistemas sanitarios que muchos países no han podido superar. En nuestro país incluso se ha visto afectada la relación entre los profesionales de las ciencias de la salud, los pacientes y sus familias, en parte inducida por un estado desorganizado, que al seguir lineamientos de otras realidades sobre el manejo de pacientes bajo ciertos estándares del estado de salud, se han estipulado normativas que influyen en el tratamiento y pronóstico de la vida de la persona afectada, observándose atentados contra la dignidad del ser persona, de igual forma el desabastecimiento de los recursos, la corrupción y la pobre capacidad resolutiva del diagnóstico viral, no solo han permitido que se desconozca en tiempo real la enfermedad en nuestro país, sino que ha conllevado al desánimo de los profesionales como médicos y enfermeras, quienes al brindar atención y cuidado, a la variedad de estos pacientes también experimentan incapacidad, y vulnerabilidad ante la pandemia. En este sentido creemos necesario repensar sobre el impacto de la pandemia en nuestra población, así como en nuestro sistema de salud, para lo cual es importante volver al estudio de la atención sanitaria, el cuidado humano integral, modelos o corrientes en bioética vigentes, principios éticos personalistas para su abordaje; con la finalidad de brindar unos lineamientos y recomendaciones a tener en cuenta en la gestión y practica biomédica ante la crisis causada por el SARS-CoV-2.

SUMMARY The worldwide spread of the COVID-19 pandemic has triggered an international sanitary crisis that many countries could not tackle. In our country the relationship among the health care professionals their patients and relatives has been affected, in part due to a disorganized governmental response to the pandemic that dictated incorrect treatment recommendations based on foreign experiences resulting in severe attempts against the individual dignity. On the other hand, the lack of resources, the rampant corruption and the poor resolution capacity for diagnosing cases leaded not only of knowing the magnitude of the pandemic in the country but also to discouragement among health care professionals who are at the frontline experiencing fear and vulnerability. We do believe that we need to rethink on the impact of the pandemic in the country as well as on the critical reforms needed in our health care system promoting integrated human care, following current bioethical models and personalized ethical principles in order to improve current medical practices during the COVID-19 pandemic.

Educar en Bioética: el rol del directivo en el proceso de enseñanza del profesional de las ciencias de la salud / Educate in Bioethics: the role of the manager in the teaching process of the professional health sciences

En función de las necesidades de investigación en formación de recursos humanos poco abordado en nuestro medio, y partiendo de la experiencia de vida dedicados a la docencia universitaria por parte de los autores, pretendemos realizar un análisis y propuesta sobre las cualidades profesionales y personales que debe poseer un directivo u autoridad académica en el campo de las ciencias de la salud. Para llegar a desarrollar un cargo de directivo dentro de la vida universitaria proponemos que la persona debe contar con una trayectoria académica y profesional reconocida y secuencial, con sólidos conocimientos en la gestión de la universidad a través de la certificación de un entrenamiento o programa de postgrado, así como también el haber plasmado en su quehacer académico la metodología de la investigación científica evidenciado en la publicación de obras que son consultadas por sus pares y estudiantes, asimismo es imprescindible que el directivo académico sea un ejemplo a seguir, sea ético, es decir que muestre coherencia entre su vida profesional y personal. En resumen, proponemos que para ser elegido autoridad en nuestro sistema universitario no basta cumplir con los requisitos que nos propone la ley, sino que deberíamos observar estas cualidades que a manera de propuesta creemos que sería determinantes para el buen gobierno de nuestras escuelas y/o facultades de ciencias de la salud. (AU)

Depending on the research needs in human resources training little addressed in our environment, and based on the experience of life dedicated to university teaching by the authors, we intend to carry out an analysis and proposal on the Professional and personal qualities that an executive or academic authority must possess in the field of health sciences. In order to develop an executive position within the university life we propose that the person must have an academic and professional trajectory recognized and sequential, with solid knowledge in the management of the university through the certification of a training or postgraduate program, as well as having reflected in his academic work the methodology of scientific research evidenced in the publication of works that are consulted by his peers and students, it is also imperative that the academic executive is an example to follow, be ethical, that is to show consistency between your professional and personal life. In summary we propose that to be elected authority in our university system is not enough to meet the requirements of the law, but we should observe these qualities that as a proposal we believe would be determinants for good governance of our schools and/or faculties of health sciences. (AU)