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Cancer is an increasing global public health burden. Lately, more emphasis has emerged on the importance of heredity in cancer, mostly driven by the introduction of germline genetic variants–directed therapeutics. It is true that 40% of cancer risk is attributed to modifiable environmental and lifestyle factors; still, 16% of cancers could be heritable, accounting for 2.9 of the 18.1 million cases diagnosed worldwide. At least two third of those will be diagnosed in countries with limited resources—low- and middle-income countries, especially where high rates of consanguine marriage and early age at diagnosis are already prevalent. Both are hallmarks of hereditary cancer. This creates a new opportunity for prevention, early detection, and recently therapeutic intervention. However, this opportunity is challenged by many obstacles along the path to addressing germline testing in patients with cancer in the clinic worldwide. Global collaboration and expertise exchange are important to bridge the knowledge gap and facilitate practical implementation. Adapting existing guidelines and prioritization according to local resources are essential to address the unique needs and overcome the unique barriers of each society.

The prevalence and contribution of BRCA1/2 (BRCA) pathogenic variants (PVs) to the cancer burden in Latin America are not well understood. This study aims to address this disparity. BRCA analyses were performed on prospectively enrolled Latin American Clinical Cancer Genomics Community Research Network participants via a combination of methods: a Hispanic Mutation Panel (HISPANEL) on MassARRAY; semiconductor sequencing; and copy number variant (CNV) detection. BRCA PV probability was calculated using BRCAPRO. Among 1,627 participants (95.2% with cancer), we detected 236 (14.5%) BRCA PVs; 160 BRCA1 (31% CNVs); 76 BRCA2 PV frequency varied by country: 26% Brazil, 9% Colombia, 13% Peru, and 17% Mexico. Recurrent PVs (seen ≥3 times), some region-specific, represented 42.8% (101/236) of PVs. There was no ClinVar entry for 14% (17/125) of unique PVs, and 57% (111/196) of unique VUS. The area under the ROC curve for BRCAPRO was 0.76. In summary, we implemented a low-cost BRCA testing strategy and documented a significant burden of non-ClinVar reported BRCA PVs among Latin Americans. There are recurrent, population-specific PVs and CNVs, and we note that the BRCAPRO mutation probability model performs adequately. This study helps address the gap in our understanding of BRCA-associated cancer in Latin America.

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Benign tumors that grow in the spinal canal are heterogeneous neoplasms with low incidence; from these, meningiomas and nerve sheath tumors (neurofibromas and schwannomas) account for 60%-70% of all primary spinal tumors. Benign spinal canal tumors provoke nonspecific clinical manifestations, mostly related to the affected level of the spinal cord. These tumors present a challenge for the patient and healthcare professionals, for they are often difficult to diagnose and the high frequency of posttreatment complications. In this review, we describe the epidemiology, risk factors, clinical features, diagnosis, histopathology, molecular biology, and treatment of extramedullary benign meningiomas, osteoid osteomas, osteoblastomas, aneurysmal bone cysts, osteochondromas, neurofibromas, giant cell tumors of the bone, eosinophilic granulomas, hemangiomas, lipomas, and schwannomas located in the spine, as well as possible future targets that could lead to an improvement in their management.

Objective: The aim of this study is to estimate the incidence of COVID-19 in a vaccinated and an unvaccinated group of adolescents and describe their symptoms. Methods: In May 2021 a private indoor event for high school adolescents took place resulting in a superspreading event. As part of the study, an anonymous questionnaire was sent to all adolescents invited to the event and details about symptoms, previous COVID-19 infection, vaccination status and behaviour during the event was assessed. Two groups were formed, one of vaccinated individuals and the other of unvaccinated individuals. A sample from a fully vaccinated symptomatic individual was sequenced. General characteristics for the studied groups are described using categorical and continuous data. The incidence of COVID-19 in each group was estimated by taking the total number of COVID-19 positive cases (numerator) divided by the total number of individuals (denominator) multiplied by 100. Results: A total of 41 out of the 164 adolescents (incidence 25%, 95%CI 18.6- 32.4) that attended the private indoor event developed COVID-19. A sample was sequenced from one of the symptomatic and fully vaccinated individuals with BNT162b2 (Pfizer-BioNTech vaccine) finding SARS-CoV-2 Delta (B.1.617.2) variant of concern. The incidence of COVID-19 in the unvaccinated was 35.1% (95%CI 25.5-45.6), and in the vaccinated 11.4% (95%CI 5.1-21.3). There were more unvaccinated than vaccinated teenagers that developed COVID-19

Background Patients with familial erythrocytosis type 2 have no increased risk of von Hippel-Lindau-associated tumors, although mutations in the VHL gene cause both pathologies. Case report We present a case of a compound heterozygote patient with von Hippel-Lindau disease and familial erythrocytosis type 2. One of the mutations found in our patient, c.416C>G (p.Ser139Cys) of the VHL gene, has not been previously reported. This case is the second one reported where von Hippel-Lindau disease and familial erythrocytosis type 2 coexist in the same individual. Conclusions Despite the low frequency of familial erythrocytosis type 2 in patients with von Hippel-Lindau disease, the possibility of this diagnosis should be considered to avoid unnecessary invasive studies to explain the polyglobulia in these patients and guarantee an adequate follow-up and vigilance of both diseases.

The present review aimed to discuss contemporary scientific literature involving differences between the tumor microenvironment (TME) in melanoma, lung cancer, and breast cancer in their primary site and TME in brain metastases (BM). TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, natural killer cells, and other cells can perpetuate and progress carcinogenesis via the secretion of molecules. Oxygen concentration, growth factors, and receptors in TME initiate angiogenesis and are examples of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant brain tumors are metastatic in origin and primarily originate from lung cancer, breast cancer, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood–brain barrier (BBB). After traversing BBB, these cells have to survive by producing various cytokines, chemokines, and mediators to modify their new TME. The microenvironment of these metastases is currently being studied owing to the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in BM due to several factors, including BBB. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might help improve strategies to comprehend cancer.

Denisse Arcos-Montoya,1 Talia Wegman-Ostrosky,2,3 Sonia Mejía-Pérez,4 Marisol De la Fuente-Granada,1 Ignacio Camacho-Arroyo,5 Alejandro García-Carrancá,6 Marco A Velasco-Velázquez,7 Joaquín Manjarrez-Marmolejo,8 Aliesha González-Arenas1 1Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México; 2Dirección de Investigación, Instituto Nacional Cancerología, Ciudad de México, México; 3División de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, México; 4Subdirección de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México; 5Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México; 6Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México e Instituto Nacional de Cancerología, Ciudad de México, México; 7Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México; 8Laboratorio de Fisiología de la Formación Reticular, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, MéxicoCorrespondence: Aliesha González-ArenasDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, 04510, MéxicoTel +52 5556 22 9209Email alieshag@iibiomedicas.unam.mxIntroduction: Astrocytomas are the most common and aggressive primary brain tumors, and they are classified according to the degree of malignancy on a scale of I to IV, in which grade I is the least malignant and grade IV the highest. Many factors are related to astrocytomas progression as progesterone receptor (PR), whose transcriptional activity could be regulated by phosphorylation by protein kinase C alpha (PKCα) at the residue Ser400. Our aim was to investigate if PR phosphorylation together with PKCα expression could be used as a prognostic factor for astrocytomas malignancy.Methods: By immunofluorescence, we detected the content of PKCα, PR and its phosphorylation at Ser400 in 46 biopsies from Mexican patients with different astrocytoma malignancy grades; by bioinformatic tools using TCGA data, we evaluated the expression of PR and PKCα mRNA according to astrocytoma malignancy grades. For all statistical analyses, significance was p< 0.05.Results: We detected a positive correlation between the tumor grade and the content of PKCα, PR and its phosphorylation at Ser400, as well as the intracellular colocalization of these proteins. Interestingly, using an in silico assay, we found that the PR and PKCα expression at mRNA level has an inverse ratio with astrocytomas tumor grade.Discussion: These results indicate that PR and its phosphorylation at Ser400 site, as well as PKCα and their colocalization, could be considered as possible malignancy biomarkers for astrocytomas grades I–IV.Keywords: astrocytoma, glioblastoma, progesterone receptor, protein kinase C alpha, biomarker

Summary Background Li-Fraumeni syndrome, caused primarily by pathogenic or likely pathogenic germline TP53 variants, is a rare, variably penetrant, cancer predisposition syndrome with very high risks of cancer starting in childhood, including the risk of multiple primary malignancies over an individual's lifespan. We aimed to characterise and quantify cancer incidence, patterns, and genotype–phenotype associations in individuals with pathogenic or likely pathogenic germline TP53 variants. Methods This observational cohort study was done in 480 carriers of pathogenic or likely pathogenic germline TP53 variants enrolled in the National Cancer Institute's referral-based longitudinal Li-Fraumeni syndrome study between Aug 1, 2011, and March 24, 2020. Data on personal and family history of cancer were obtained through study questionnaires and validated by medical records. Variants were categorised on the basis of both loss-of-function (LOF) and dominant-negative effect (DNE) properties. Cancer incidence associated with Li-Fraumeni syndrome was compared with that of the general population using the Surveillance, Epidemiology, and End Results (SEER) 1975–2017 registry. Cancer incidence was evaluated with family-clustered Cox regression models and competing risk methods. This study is registered with ClinicalTrials.gov , NCT01443468 . Findings Individuals with Li-Fraumeni syndrome had a nearly 24 times higher incidence of any cancer than the general population (standardised incidence ratio 23·9; 95% CI 21·9–26·0), with the highest comparative incidence from childhood to 30 years of age. The overall cancer incidence remained 10·3 (95% CI 7·9–13·2) times higher than that of the general population after age 50 years. In women, when considering breast cancer as a competing risk, the probability of a first diagnosis of a non-breast cancer malignancy was substantially lower than that of any first cancer (24·4% [95% CI 19·6–30·5] vs 50·4% [43·5–56·5] by age 33·7 years). Overall, DNE_LOF and notDNE_LOF variants were associated with earlier age at first and second cancer compared with notDNE_notLOF and DNE_notLOF variants. The time interval from first to second cancer was shorter among carriers whose first cancer diagnoses were later in life. Multiple cancers were diagnosed within a short timeframe in some individuals, regardless of the order of cancer occurrence. Interpretation This study adds granularity to the understanding of cancer incidence and patterns in individuals with pathogenic or likely pathogenic germline TP53 variants. Integration of age range-specific cancer incidence estimates, cancer-free survival by functional variant group, the potential impact of risk-reducing mastectomy on female cancer incidence, and data on subsequent malignancies will be important for the development of strategies to optimise cancer screening and management for these individuals. Funding Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Institutes of Health.

PURPOSE Previous studies have shown an approximately two-fold elevation in the relative risk of urinary bladder cancer (UBC) among people with a family history that could not be entirely explained by shared environmental exposures, thus suggesting a genetic component in its predisposition. Multiple genome-wide association studies and recent gene panel sequencing studies identified several genetic loci that are associated with UBC risk; however, the list of UBC-associated variants and genes is incomplete. MATERIALS AND METHODS We exome sequenced eight patients from three multiplex UBC pedigrees and a group of 77 unrelated familial UBC cases matched to 241 cancer-free controls. In addition, we examined pathogenic germline variation in 444 candidate genes in 392 The Cancer Genome Atlas UBC cases. RESULTS In the pedigrees, segregating variants were family-specific although the identified genes clustered in common pathways, most notably DNA repair ( MLH1 and MSH2) and cellular metabolism ( IDH1 and ME1). In the familial UBC group, the proportion of pathogenic and likely pathogenic variants was significantly higher in cases compared with controls ( P = .003). Pathogenic and likely pathogenic variant load was also significantly increased in genes involved in cilia biogenesis ( P = .001). In addition, a pathogenic variant in CHEK2 (NM_007194.4:c.1100del; p.T367Mfs*15) was over-represented in cases (variant frequency = 2.6%; 95% CI, 0.71 to 6.52) compared with controls (variant frequency = 0.21%; 95% CI, 0.01 to 1.15), but was not statistically significant. CONCLUSION These results point to a complex polygenic predisposition to UBC. Despite heterogeneity, the genes cluster in several biologically relevant pathways and processes, for example, DNA repair, cilia biogenesis, and cellular metabolism. Larger studies are required to determine the importance of CHEK2 in UBC etiology.

Background. COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. Methods. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I2 statistics. This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines, although the study protocol was not registered. Results. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 14 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). Conclusions. In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, the severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

Background Pediatric cancers are the leading cause of death by disease in children despite improved survival rates overall. The contribution of germline genetic susceptibility to pediatric cancer survivors has not been extensively characterized. We assessed the frequency of pathogenic or likely pathogenic (P/LP) variants in 5451 long-term pediatric cancer survivors from the Childhood Cancer Survivor Study. Methods Exome sequencing was conducted on germline DNA from 5451 pediatric cancer survivors (cases who survived ≥5 years from diagnosis; n = 5105 European) and 597 European cancer-free adults (controls). Analyses focused on comparing the frequency of rare P/LP variants in 237 cancer-susceptibility genes and a subset of 60 autosomal dominant high-to-moderate penetrance genes, for both case-case and case-control comparisons. Results Of European cases, 4.1% harbored a P/LP variant in high-to-moderate penetrance autosomal dominant genes compared with 1.3% in controls (2-sided P = 3 × 10-4). The highest frequency of P/LP variants was in genes typically associated with adult onset rather than pediatric cancers, including BRCA1/2, FH, PALB2, PMS2, and CDKN2A. A statistically significant excess of P/LP variants, after correction for multiple tests, was detected in patients with central nervous system cancers (NF1, SUFU, TSC1, PTCH2), Wilms tumor (WT1, REST), non-Hodgkin lymphoma (PMS2), and soft tissue sarcomas (SDHB, DICER1, TP53, ERCC4, FGFR3) compared with other pediatric cancers. Conclusion In long-term pediatric cancer survivors, we identified P/LP variants in cancer-susceptibility genes not previously associated with pediatric cancer as well as confirmed known associations. Further characterization of variants in these genes in pediatric cancer will be important to provide optimal genetic counseling for patients and their families.

PURPOSE Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts. MATERIALS AND METHODS Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort. RESULTS We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants ( ATM, CDKN1C) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with FOXO1 fusion–negative RMS patients versus the patients with FOXO1 fusion–positive RMS. We identified pathogenic germline variants in CSGs previously ( TP53, NF1, DICER1, mismatch repair genes), rarely ( BRCA2, CBL, CHEK2, SMARCA4), or never ( FGFR4) reported in RMS. Numerous genes ( TP53, BRCA2, mismatch repair) were on the ACMG Secondary Findings 2.0 list. CONCLUSION In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.

Gene therapy is an experimental technique that uses genes to treat or prevent disease. In gliomas different strategies have use: (1) release of suicide genes to produce cytotoxic compounds in the tumor and provoke tumor cell death, (2) oncolytic virotherapy, (3) release of tumor-suppressor genes, (4) immunomodulatory gene therapy, that stimulates an antitumoral immune response, and (5) the use of synthetic vector particles/nanoparticles to deliver genetic material thereby silencing genes essential to tumorigenesis. Several clinical trails have use gene therapy alone or with other therapies in gliomas, but at the time there is not any gene therapy approve for treatment or prevention in gliomas.

In recent years, multiple biomarkers have emerged in the field of neuro-oncology, with useful applications in improving diagnostic accuracy, establishing patient’s prognosis and predictive response to available medical therapy. The most frequently associated biomarkers, and their respective alterations, include, IDH1/2 mutation, 1p/19q codeletion, ATRX loss, TP53 mutation, MGMT promoter methylation, BRAF and H3 mutations. In this chapter, we review these biomarkers, but also other less understood ones involved in the diagnosis, prognosis and the treatment of gliomas, such as ABC transporters, AGT mutations, G-CIMP mutation, PTEN mutation, among others. We also include two algorithms for molecular-based decision-making for pediatric and adult gliomas and tables with comprehensive information of biomarkers in gliomas.

The present review aims to discuss the contemporary medical literature involving the variances between the tumor microenvironment (TME) mainly in melanoma, lung, and breast cancer in their original primary site and compare them with their brain metastases (BM). The TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, NK cells, etc., through the secretion of molecules can perpetuate and progress carcinogenesis. The conditions at the TME, such as oxygen concentration, growth factors, and receptors, generate the beginning of angiogenesis; this is an example of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant tumors of the brain are metastatic in origin, mainly from lung, breast, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood brain barrier (BBB); after passing through the BBB they have to survive by producing a variety of cytokines, chemokines and mediators to modify their new TME. A field currently studied is the microenvironment of these metastases, since this has brought about the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in the BM, due to many factors including the blood brain barrier. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might improve strategies to grasp cancer behavior. This chapter will focus on the relationship between the tumor microenvironment of primary origin tumor and their corresponding brain metastases.

El objetivo de este artículo es revisar la literatura médica y científica (incluida una revisión paraguas) relacionada con el uso de cubrebocas como medida de prevención en la transmisión de enfermedades respiratorias virales para tomar decisiones informadas durante una pandemia. Desde inicios del siglo XX se estableció que el cubrebocas es efectivo para reducir infecciones respiratorias. El uso entre la población general inició hasta la pandemia de 1918. Desde entonces, las investigaciones se han enfocado principalmente en determinar los mejores materiales para su elaboración, encontrando que la efectividad del cubrebocas aumenta con el número de las capas, siendo ideal tres, de punto cerrado y de diversos materiales. Los meta-análisis demostraron que el uso de cubrebocas disminuye el riesgo de contagio de enfermedades respiratorias virales, incluido COVID-19, comparado a no usarlo. Los cubrebocas evitan el paso de una gran proporción de partículas del virus SARS-CoV-2 protegiendo tanto al portador como al resto de la población al reducir la carga viral a la que se está expuesto, disminuyendo así el riesgo de desarrollar enfermedad grave de COVID-19. Cuando las personas están en espacios públicos es preferible elegir usar cualquier cubrebocas, a no usar ninguna protección naso bucal. Para decidir sobre el uso del cubrebocas es importante evaluar el riesgo-beneficio. Con este análisis concluimos que según la evidencia, los beneficios del uso del cubrebocas superan los riesgos, por lo que recomendamos que el uso de cubrebocas de forma generalizada.

The angiotensin-converting enzyme 2 (ACE2) is the host functional receptor for the new virus SARS-CoV-2 causing Coronavirus Disease 2019. ACE2 is expressed in 71 different cell types. Some factors that can affect the expression of the ACE2 are: sex, environment, lifestyles, comorbidities, medications (e.g. anti-hypertensives) and its interaction with other genes of the renin-angiotensin system and other pathways. All of these factors can affect the risk of infection of SARS-CoV-2 and determine the severity of the symptoms. The ACE2 enzyme is a negative regulator of RAS expressed in various organ systems. It has been seen to be associated with immunity, inflammation, increased coagulopathy, and cardiovascular disease. In this review, we describe the genetic and molecular functions of the ACE2 receptor and its relation with the physiological and pathological conditions to better understand how this receptor is involved in the pathogenesis of COVID-19.

Young women with breast cancer represent 15% of cancer cases in Latin America. Genomic studies have found that early-onset breast-cancer cases exhibit a higher genetic susceptibility and a specific genomic signature as compared to their older counterparts. The aim of this study was to describe clinically relevant germline mutations in a cohort of young women with breast cancer. To achieve this, we analyzed hereditary-cancer genes from whole-exome sequencing data in 108 unrelated women with an extreme phenotype of breast cancer (≤40 years of age), diagnosed and treated at the National Cancer Institute of Mexico; 11% of the patients carried a pathogenic variant. BRCA2 comprised 46% of the mutations, followed by BRCA1 with 23%; PALB2 with 15%; and TP53 and RAD51C with 8 % each. This article describes a novel pathogenic mutation in RAD51C c.519dupT. The median age at diagnosis was 35 years overall; however, it was six years younger in patients with mutations. Age at diagnosis (OR=0.82, CI 95% 0.71-0.94; P= 0.008) and first-degree family history of cancer (OR=8.26, CI95% 1.35-50; P= 0.022) were the only epidemiological variables associated with mutational status. We found no differences in disease-free survival (p=0.403) or overall survival (p=0.735) among mutational status subgroups.

Background Substance use disorders (SUD) are a category of psychiatric disorders with a large epidemiological and societal impact around the world. In the last decades, a large number of genetic studies have been published for SUDs. Methods With the objective of having an overview and summarizing the evidence published up to date, we carried out an umbrella review of all the meta-analyses of genetic studies for the following substances: alcohol, tobacco, cannabis, cocaine, opioids, heroin and methamphetamines. Meta-analyses for candidate gene studies and genome-wide association studies (GWAS) were included. Results Alcohol and tobacco were the substances with the largest number of meta-analyses, and cannabis, opioids and cocaine the least studied. The following genes were associated with two or more SUDs: OPRM1, DRD2, DRD4, BDNF and SL6A4. The only genes that had an OR higher than two were the SLC6A4 for all addictions, the ADH1B for alcohol dependence, and BDNF for methamphetamine dependence. GWAS confirmed the possible role of CHRNA5 gene in nicotine dependence and identified novel candidate genes in other SUDs, such as FOXP2, PEX and, AUTS2, which need further functional analyses. Conclusions This umbrella review summarizes the evidence of 16 years of research on the genetics of SUDs and provides a broad and detailed overview of results from more than 150 meta-analyses for SUD. The results of this umbrella review will guide the need for future genetic studies geared toward understanding, preventing and treating SUDs.

Objectives Breast cancer (BC) is the leading cause of morbidity and mortality. Neurological symptoms are highly feared because they are associated with central nervous system metastases (CNSm). So, we aimed to analyze the association of neurological symptoms with CNSm. Patients & Methods Patients with BC referred for a neuro-oncological evaluation at a cancer referral center from June 2012 to December 2017 were included. Demographic, oncological history, comorbidities, clinical symptoms and signs, and their correlation with CNSm were prospectively acquired during consultation in a computerized database. Analyses included descriptive observations, bivariate, and logistic linear regression tests that compared associations. Results A total of 857 patients with BC were referred for assessment. The most frequently occurring symptoms included headache, focal motor weakness, focal-sensitive complaints, and visual complaints. Of the 1029 neuro-oncology diagnoses made, the most common were CNSm, primary headache, and chemotherapy-induced neuropathy. The risk factors associated with CNSm in patients with neurological symptoms were HER2+, younger age at cancer diagnosis, presence of extracranial metastases, and >1 neurological symptom (mainly headache: hazard ratio (HR), 2.1 [95% confidence interval (CI), 1.5–2.7]; visual complaints: HR, 2.3 (95%CI, 1.2–4.2); and ataxia: HR, 2.1 (95%CI,1.04–4.3). Conclusions Clinical symptoms and cancer characteristics were correlated with the development of CNSm. Specific risk and protective factors were identified. Among BC patients with neurological symptoms, CNSm should always be considered, especially in patients with certain oncological and clinical features.

Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with adjuvant therapy have a mean overall survival of 15 months and 100% recurrence. The renin-angiotensin system (RAS), the primary regulator of cardiovascular circulation, exhibits local action and works as a paracrine system. In the context of this local regulation, the expression of RAS peptides and receptors has been detected in different kinds of tumors, including gliomas. The dysregulation of RAS components plays a significant role in the proliferation, angiogenesis, and invasion of these tumors, and therefore in their outcomes. The study and potential application of RAS peptides and receptors as biomarkers in gliomas could bring advantages against the limitations of current tumoral markers and should be considered in the future. The targeting of RAS components by RAS blockers has shown potential of being protective against cancer and improving immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for beneficial effects and are being considered for use in treatment protocols. This review aims to summarize the background behind how RAS plays a role in gliomagenesis and explore the evidence that could lead to their use as biomarkers and treatment adjuvants.

Breast cancer (BC) in young women, generally defined in oncology as women who are 40 years of age or younger, represents 2 out of 10 BC cases in developing countries. Several research studies, including genetic cancer panel tests, genome-wide association studies, expression analyses and polymorphisms reports, have found that young women with BC exhibit a higher genetic susceptibility and specific genomic signature compared to postmenopausal women with BC. Thus, international guidelines recommend genetic counseling for this age population. This review presents the current state of the art of genetics and genomics with regards to young women with BC.

The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients. Herein we review the clinical features, underlying biology, and new genomic discoveries in the IBMFS, including Fanconi anaemia, dyskeratosis congenita, Diamond Blackfan anaemia, Shwachman Diamond syndrome and some disorders of the myeloid and megakaryocytic lineages.

This chapter presents an overview of the influence that pharmacogenomics and pharmacogenetics have on each of the phases of traditional drug development and how the process is being rewritten to adapt to these new technologies. Thousands of new candidate molecules are being introduced to treat genetic diseases for which there was no hope, and drugs with novel mechanisms of action are being developed to target complex diseases such as cancer. In basic and preclinical research, genetic information is guiding drug discovery, and during the clinical phases it is identifying the variability in the response that patients have (both efficacy and safety) to pharmacologic agents. The first part of the chapter describes how new technologies use genomic tools and epigenetic mechanisms such as methylation and histone modifications as part of the development of new drugs that can lead to precision medicine. The second part of the chapter reviews the molecular techniques used in genetic therapies, which includes gene replacement such as gene therapy, gene editing, including the use of the nuclease zinc-finger nucleases and CRISP, gene silencing that involves RNAi therapy, antisense oligonucleotides, and epigenetic therapies. Approved genetic drugs as well as genetic drugs in development are presented.

Objective To explore the clinical prognostic factors for adults affected with astrocytoma. Patients and methods Using a historic cohort, we selected 155 clinical files from patients with astrocytoma using simple randomization. The main outcome variable was overall survival time. To identify clinical prognostic factors, we used bivariate analysis, Kaplan Meier, the log rank test and the Cox regression models. The number of lost years lived with disability (DALY) based on prevalence, was calculated. Results The mean age at diagnosis was 45.7 years. Analysis according to tumour stage, including grades II, III and IV, also showed a younger age of presentation. Kaplan-Meier survival estimates showed that tumour grade, Karnofsky status (KPS) ≥70, resection type, chemotherapy, radiotherapy, alcohol consumption, familial history of cancer and clinical presentation were significantly associated with survival time. Using a proportional hazard model, age, grade IV, resection, chemotherapy + radiotherapy and KPS were identified as prognostic factors.The amount of life lost due to premature death in this population was 28 years. Conclusion In our study, astrocytoma was diagnosed in young adults. The overall survival was 15 months, 9% (n = 14) of patients presented a survival of 2 years, and 3% of patients survived 3 years. On average the number of years lost due to premature death and disability was 28.53 years.

Background Prior research has established that the prevalence of pathogenic/likely pathogenic (P/LP) variants across all of the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes is approximately 0.8–5%. We investigated the prevalence of P/LP variants in the 24 ACMG SF v2.0 cancer genes in a family-based cancer research cohort (n = 1173) and in cancer-free ethnicity-matched controls (n = 982). Methods We used InterVar to classify variants and subsequently conducted a manual review to further examine variants of unknown significance (VUS). Results In the 24 genes on the ACMG SF v2.0 list associated with a cancer phenotype, we observed 8 P/LP unique variants (8 individuals; 0.8%) in controls and 11 P/LP unique variants (14 individuals; 1.2%) in cases, a non-significant difference. We reviewed 115 VUS. The median estimated per-variant review time required was 30 min; the first variant within a gene took significantly (p = 0.0009) longer to review (median = 60 min) compared with subsequent variants (median = 30 min). The concordance rate was 83.3% for the variants examined by two reviewers. Conclusion The 115 VUS required database and literature review, a time- and labor-intensive process hampered by the difficulty in interpreting conflicting P/LP determinations. By rigorously investigating the 24 ACMG SF v2.0 cancer genes, our work establishes a benchmark P/LP variant prevalence rate in a familial cancer cohort and controls. Electronic supplementary material The online version of this article (10.1186/s13073-018-0607-5) contains supplementary material, which is available to authorized users.

Angiotensin II (ANGII) has been associated with vascular proliferation in tumor and non-tumor models through its receptors AT1 and AT2. Our objective was to determine AT1 and AT2 receptor expression in operable breast cancer and its association with tumor grade, vascular density, and cellular proliferation. Seventy-seven surgically malignant breast tumors with no distant metastasis were included, and 7 benign lesions were used as controls. AT1 and AT2 receptor expression was determined by RT-PCR and immunohistochemistry (IHC) in 68 out of the 77 malignant lesions and in the 7 benign lesions. AT1 and AT2 receptor expression was detected in 35.3 and 25 % of cases, in both RT-PCR and IHC. Tumors that express AT1 showed an increase in T3 stage (92.3 vs. 7.7 % p < 0.001), mitotic index (4 ± 1 vs 2 ± 1, p = 0.05), vascular density (15 ± 3 vs 8 ± 5, p = 0.05), and cellular proliferation (85 ± 18 vs 55 ± 10, p = 0.01) versus AT1-negative lesions. Non-differences between clinical-pathologic variables and AT2 expression were found. AT1 receptor expression was associated to enhance angiogenesis and cellular proliferation rate, but no relationship with AT2 was found. ANGII and its peptides might play a role in the development and pathophysiology of breast cancer, and this could be valuable in the in the development of targeted therapies.

The deletion of exons 9 to 12 of BRCA1 (9-12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9-12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9-12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9-12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9-12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9-12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9-12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer.