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Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9-12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9-12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT-qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9-12 alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9-12 and identifying which of them has developed cancer.
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Alelos , Proteína BRCA1 , Síndrome Hereditária de Câncer de Mama e Ovário , Humanos , Proteína BRCA1/genética , Feminino , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Pessoa de Meia-Idade , Predisposição Genética para Doença , Adulto , Efeito Fundador , Éxons/genética , Neoplasias da Mama/genética , Heterozigoto , Mutação , México , Neoplasias Ovarianas/genética , Relevância ClínicaRESUMO
OBJECTIVE: To characterize the impact of SARS-CoV-2 infection in workers from an essential large-scale company in the Greater Mexico City Metropolitan Area using point prevalence of acute infection, point prevalence of past infection through serum antibodies and respiratory disease short-term disability claims (RD-STDC). MATERIALS AND METHODS: Four randomized surveys, three during 2020 before and one after (December 2021) vaccines' availability. OUTCOMES: point prevalence of acute infection through saliva PCR (polymerase chain reaction) testing, point prevalence of past infection through serum antibodies against Covid-19, RD-STDC and prevalence of symptoms during the previous six months. RESULTS: Prevalence of SARS-CoV-2 cases was 1.29-4.88%, on average, a quarter of participants pre-vaccination were seropositive; over half of participants with a RD-STDC had antibodies. The odds of having antibodies were 6-7 times more among workers with an RD-STDC. CONCLUSIONS: High antibody levels against Covid-19 in this study population reflects that coverage is high among workers in this industry. STDCs are a useful tool to track workplace epidemics.
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COVID-19 , Epidemias , Humanos , SARS-CoV-2 , México/epidemiologia , Estudos Soroepidemiológicos , COVID-19/epidemiologia , Anticorpos AntiviraisRESUMO
BACKGROUND: Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. OBJECTIVES: To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. MATERIAL AND METHODS: Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. RESULTS: One-hundred and twenty-seven CPs (22%) and 439 HCWs (78%) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. CONCLUSIONS: The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.
ANTECEDENTES: La vacunación es la intervención más efectiva para reducir la carga de enfermedad por SARS-CoV-2; sin embargo, persisten brechas en el conocimiento en relación con la respuesta inmunológica de los pacientes con cáncer (PC). OBJETIVOS: Evaluar la respuesta humoral (anticuerpos anti-S) en PC y trabajadores de salud (TS) vacunados con dos dosis de la vacuna BNT162b2 o AZD122. MATERIAL Y MÉTODOS: Se cuantificaron anticuerpos poliespecíficos contra la proteína de espiga de SARS-CoV-2 (anti-S) y se efectuó una puntuación de propensión 1:1 para equilibrar las características basales. Se realizaron regresiones logísticas múltiples para evaluar el efecto de las variables relacionadas con la respuesta humoral. RESULTADOS: Se incluyeron 127 PC (22 %) y 439 TS (78 %). Ambas poblaciones desarrollaron anticuerpos anti-S en respuesta a la vacunación. La vacuna de ARNm (BNT162b2) se asoció a mayor probabilidad de mostrar concentraciones de anticuerpos anti-S ≥ 1000 UI/mL, mientras que el cáncer activo se relacionó con menor probabilidad de presentar títulos altos de anticuerpos. CONCLUSIONES: La vacuna BNT162b2 se asoció a respuesta humoral mayor. Es necesario contar con más información y estrategias de vacunación en pacientes inmunosuprimidos. Es relevante la selección de los mejores biológicos para esta población y considerar las características individuales.
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COVID-19 , Neoplasias , Humanos , Prevalência , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Pessoal de SaúdeRESUMO
Resumen Antecedentes: La vacunación es la intervención más efectiva para reducir la carga de enfermedad por SARS-CoV-2; sin embargo, persisten brechas en el conocimiento en relación con la respuesta inmunológica de los pacientes con cáncer (PC). Objetivos: Evaluar la respuesta humoral (anticuerpos anti-S) en PC y trabajadores de salud (TS) vacunados con dos dosis de la vacuna BNT162b2 o AZD122. Material y métodos: Se cuantificaron anticuerpos poliespecíficos contra la proteína de espiga de SARS-CoV-2 (anti-S) y se efectuó una puntuación de propensión 1:1 para equilibrar las características basales. Se realizaron regresiones logísticas múltiples para evaluar el efecto de las variables relacionadas con la respuesta humoral. Resultados: Se incluyeron 127 PC (22 %) y 439 TS (78 %). Ambas poblaciones desarrollaron anticuerpos anti-S en respuesta a la vacunación. La vacuna de ARNm (BNT162b2) se asoció a mayor probabilidad de mostrar concentraciones de anticuerpos anti-S ≥ 1000 UI/mL, mientras que el cáncer activo se relacionó con menor probabilidad de presentar títulos altos de anticuerpos. Conclusiones: La vacuna BNT162b2 se asoció a respuesta humoral mayor. Es necesario contar con más información y estrategias de vacunación en pacientes inmunosuprimidos. Es relevante la selección de los mejores biológicos para esta población y considerar las características individuales.
Abstract Background: Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. Objectives: To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. Material and methods: Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. Results: One-hundred and twenty-seven CPs (22 %) and 439 HCWs (78 %) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. Conclusions: The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.
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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.
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Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Inibidores de Checkpoint Imunológico , México/epidemiologia , Proteína 2 Homóloga a MutS/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City. METHODS: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated with prevention behaviors were identified by logistic regression. RESULTS: We recruited 301 workers; 77% were women. The median self-reported BMI was 26.4 kg/m2, 9.97% smoked, 78% drank alcohol, and 89% did not get at least 150 min/week of physical activity. In women, age (OR = 1.3 95%CI 1.01-1.06) and physical activity of 150 min/week (OR = 2.52 95% CI 1.28-4.96) were associated with cancer prevention behaviors. No risk factors were associated with healthy behaviors among men. CONCLUSION: Health workers may have unhealthy lifestyles and behaviors, is essential to create supportive environments to promote cancer prevention counseling and programs effectively.
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Detecção Precoce de Câncer , Neoplasias , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Masculino , México/epidemiologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Projetos Piloto , Encaminhamento e ConsultaRESUMO
Lead (Pb) is one of the most common metals found in ecosystems in elevated concentrations derived mainly from anthropogenic activities. Pb toxicity is of special concern in birds due to its capacity for bioaccumulation in the liver, bones, and kidneys causing physiological disruptions. Such disruptions can be lethal in a few days after Pb acute intoxication and they are associated with several million deaths of birds. Moreover, Pb may work as an immunosuppressant as it affects the cell-mediated and humoral immune responses, including components of the acute-phase response (APR). We (1) examined the effects of Pb contamination on the innate immune system, body mass, and food intake of Japanese quails (Coturnix coturnix japonica), and (2) evaluated the effects of Pb on its APR after exposing the animals to Pb acetate in drinkable water during 7 days. We found that Pb contamination increased the number of circulating white blood cells (WBCs), but no effect was found on body mass, food intake, the heterophil/lymphocyte (H/L) ratio, and haptoglobin (Hp) concentration. When Pb-exposed birds were injected with lipopolysaccharide from Escherichia coli to activate the APR, they had a negative body mass ratio, reduced food intake, and increased the number of WBCs, the H/L ratio, and the Hp concentration. We conclude that Pb exposure at this dose did not affect baseline values of the constitutive response and that it did not affect the APR of quails, but commend for further studies testing the effect of different Pb doses.
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Coturnix , Chumbo , Animais , Coturnix/fisiologia , Ecossistema , Imunidade Inata , Chumbo/toxicidade , CodornizRESUMO
Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients-one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.
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MicroRNAs , Neoplasias do Colo do Útero , Feminino , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/cirurgiaRESUMO
PURPOSE: Cancer treatment during the COVID-19 pandemic represents a challenge. Hospital visits to receive treatment and interaction with health care workers (HCW) represent potential contagious events. We aimed to determine SARS-CoV-2 infection rate among patients with cancer and HCW of a chemoradiotherapy unit localized in a center designated as a COVID-19 priority facility in Mexico City. We also determined the diagnostic performance of a clinical questionnaire (CQ) as a screening tool and anti-SARS-CoV-2 antibody seroconversion rate. METHODS: HCW and patients with solid tumors attending the chemoradiotherapy unit signed informed consent. To determine SARS-CoV-2 infection rate prospectively, a nasopharyngeal swab for SARS-CoV-2 real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was performed every 2 weeks in asymptomatics. An electronic CQ interrogating COVID-19-related symptoms was sent daily. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were measured at baseline and at the end of the study period. RESULTS: From June to September 2020, we included 130 asymptomatic participants, 44.6% HCW and 55.4% patients with cancer. During a median follow-up of 85 days, 634 nasopharyngeal swabs were performed. Average SARS-CoV-2 monthly incidence was 4.6% (3.15%-7.47%), and cumulative infection rate was 13.8% (18 of 130). Cases were mostly asymptomatic (66%), and no hospitalizations or deaths were recorded. The CQ as a screening tool provided a sensitivity of 27.7%, a positive predictive value of 26.3%, and a positive likelihood ratio of 12. SARS-CoV-2 IgG seroconversion rate was 27.7% among those with a positive RT-PCR. CONCLUSION: Patients with cancer on treatment can have uncomplicated COVID-19 outcomes. Biweekly RT-qPCR testing detects asymptomatic infections, prevents transmission, and should be implemented in units to increase patient safety. CQ increase RT-qPCR diagnostic yield and may prioritize testing in resource-deprived settings. Post-infection IgG seroconversion is unreliable.
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COVID-19 , Neoplasias , Quimiorradioterapia/efeitos adversos , Pessoal de Saúde , Humanos , México/epidemiologia , Neoplasias/epidemiologia , Pandemias , Estudos Prospectivos , SARS-CoV-2RESUMO
SARS-CoV-2 variants emerged in late 2020, and at least three variants of concern (B.1.1.7, B.1.351, and P1) have been reported by WHO. These variants have several substitutions in the spike protein that affect receptor binding; they exhibit increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we report the identification of a potential variant of interest, harboring the mutations T478K, P681H, and T732A in the spike protein, within the newly named lineage B.1.1.519, that rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.
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COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , COVID-19/transmissão , Genoma Viral/genética , Humanos , México/epidemiologia , Mutação , Filogenia , Prevalência , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Cancer genome sequencing methods have now become essential for diagnostic purposes, for devising treatment strategies, and for monitoring disease regression and progression. However, access to these benefits has not permeated homogeneously throughout the world; certain regions, such as Latin America, have been slower at adopting these technologies in terms of their routine use, development and patient access. There are also differences among Latin American subregions with respect to their prioritized types of neoplasia and the drugs that are available and approved in them. An overview of the current situation, including the status of genomics for cancer diagnostics and efforts by type of cancer is presented. In addition, we discuss the perspective of initiatives, alliances, and educational/research programs that pledge to make cancer genomics diagnosis a reality for Latin American individuals' health.
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Detecção Precoce de Câncer , Genoma Humano/genética , Genômica , Neoplasias/genética , Humanos , América Latina , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Sequenciamento Completo do GenomaRESUMO
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.
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Angiotensinogênio/genética , Astrocitoma/genética , Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Variação Genética/genética , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Adulto , Astrocitoma/epidemiologia , Astrocitoma/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-IdadeRESUMO
Allelic variants in genes implicated in the development of testicular germ cell tumor (TGCT) could be present in patients with cryptorchidism (CO). Currently; the mechanisms explaining this relationship are still unknown. In this study the common clinical features in patients with CO and TGCT and 6 variants of KIT and AR genes associated to TGCT were analyzed. Population analyzed included 328 individuals: 91 patients with CO; 79 with TGCT, 13 of them with previous CO diagnosis, and 158 healthy males. Of the 13 patients with TGCT and history of CO, one patient (7.7%) presented the heterozygous form of the variant rs121913507 and two patients (15.4%) presented homozygote genotype for the variant rs121913506 in KIT gene. Interestingly, the heterozygous form for the variant rs121913506 of KIT gene was identifying in all of 13 patients. The rs201934623, rs774171864, and rs12014709 variants of the AR gene did not show any clinical association. Our results strongly support that genetic component in CO could be conditioning for the development of TGCT. Notably, KIT gene variants might be determinants in the pathological association between TGCT and CO.
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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.
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Neoplasias Encefálicas , Microambiente Tumoral , Carcinogênese , Células Endoteliais , Humanos , Neovascularização PatológicaRESUMO
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.
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Proteína BRCA1/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Neoplasias da Mama/diagnóstico , Éxons/genética , Saúde da Família , Feminino , Efeito Fundador , Testes Genéticos , Humanos , México , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Deleção de Sequência , Adulto JovemRESUMO
BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.
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Neoplasias da Mama/genética , Genes p53/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa/genética , Adulto , Fatores Etários , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Estudos de Associação Genética , Variação Genética , Humanos , Síndrome de Li-Fraumeni/epidemiologia , Síndrome de Li-Fraumeni/genética , México/epidemiologia , Linhagem , Prevalência , Adulto JovemRESUMO
BACKGROUND: Cervical carcinoma (CC) is one of the most frequent neoplasms, especially in developing countries. The most common histopathological type is squamous cell carcinoma (SCC), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Prognosis according to histological type is controversial. OBJECTIVE: The objective of this study is to describe and compare the prognoses of the most common histologies of CC in the early stages. MATERIALS AND METHODS: We reviewed records of patients attended at the Instituto Nacional de Cancerología of Mexico with CC surgically treated Stages IA2-IB1 and IIA1, including the histological types SCC, AC, and ASC. Patients who had another malignant neoplasm, cervical cancer in situ, locally advanced neoplasm, and metastatic neoplasm were excluded from the study. A descriptive and comparative analysis was conducted. Overall survival (OS) and disease-free period were calculated for each histological type with the Kaplan-Meier method and were compared with the log-rank test. RESULTS: A total of 202 records were obtained, of which 131 (64.9%) had SCC, 57 (28.2%) AC, and 14 (6.9%) ASC. The 5-year DFS was 94.4% for SCC, 98.1% for AC, and 92.3% for ASC, without a statistically significant difference (p = 0.55). The 5-year OS for SCC was 97.9%, for AC was 97.8%, and for ASC was 100%, without a statistically significant difference (p = 0.702). CONCLUSIONS: DFS and OS did not differ between the most common histological types of CC at the early stages.
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Adenocarcinoma/patologia , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/epidemiologia , Adulto , Carcinoma Adenoescamoso/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , México , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/epidemiologiaRESUMO
BACKGROUND: Cervical cancer (CC) occupies fourth place in cancer incidence and mortality worldwide in women, with 560,505 new cases and 284,923 deaths per year. Approximately, nine of every ten (87%) take place in developing countries. When a macroscopic nodal involvement is discovered during a radical hysterectomy (RH), there is controversy in the literature between resect macroscopic lymph node compromise or abandonment of the surgery and sending the patient for standard chemo-radiotherapy treatment. The objective of this study is to compare the prognosis of patients with CC whom RH was abandoned and bilateral pelvic lymphadenectomy and para-aortic lymphadenectomy was performed with that of patients who were only biopsied or with removal of a suspicious lymph node, treated with concomitant radiotherapy/chemotherapy in the standard manner. METHODS: A descriptive and retrospective study was conducted in two institutions from Mexico and Colombia. Clinical records of patients with early-stage CC programmed for RH with an intraoperative finding of pelvic lymph, para-aortic nodes, or any extracervical involvement that contraindicates the continuation of surgery were obtained. Between January 2007 and December 2012, 42 clinical patients complied with study inclusion criteria and were selected for analysis. RESULTS: In patients with CC whom RH was abandoned due to lymph node affectation, there is no difference in overall survival or in disease-free period between systematic lymphadenectomy and tumor removal or lymph node biopsy, in pelvic lymph nodes as well as in para-aortic lymph nodes, when these patients receive adjuvant treatment with concomitant radiotherapy/chemotherapy. CONCLUSIONS: This is a hypothesis-generator study; thus, the recommendation is made to conduct randomized prospective studies to procure better knowledge on the impact of bilateral pelvic and para-aortic lymphadenectomy on this group of patients.
Assuntos
Adenocarcinoma/cirurgia , Aorta/cirurgia , Carcinoma de Células Escamosas/cirurgia , Histerectomia/mortalidade , Excisão de Linfonodo/mortalidade , Neoplasias Pélvicas/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/patologia , Adulto , Aorta/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pélvicas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/patologiaRESUMO
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.
Assuntos
Astrocitoma/epidemiologia , Neoplasias Encefálicas/epidemiologia , Adulto , Idoso , Astrocitoma/mortalidade , Neoplasias Encefálicas/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-IdadeRESUMO
Primary mucinous adenocarcinomas of the ovary are a diagnostic challenge because their histologic and immunohistochemical features usually overlap with metastatic tumors. SATB2 is a recently identified protein with restricted expression in the glandular cells lining the lower gastrointestinal tract. The aim of this study is to examine the differential expression of SATB2 in primary and metastatic tumors of the ovary. Mucinous ovarian tumors of intestinal type were retrieved from the pathology files of the Instituto Nacional de Cancerología de México. A double reading of the hematoxylin and eosin-stained slides was performed to confirm the diagnosis, and a detailed review of the clinical chart was performed to define the primary origin of the tumor (ovarian vs metastatic). Immunohistochemical staining for CK20, CDX2, and SATB2 was performed and evaluated by 2 gynecopathologists. A total of 106 mucinous tumors were identified, 26 of which were considered to be metastatic, and 80 of which were primary ovarian tumors. All of the primary tumors that were not associated with cystic teratomas were negative for SATB2, and the 4 that were associated with a teratoma were positive for SATB2. All 20 of the metastatic tumors of the colon and appendix were positive for CK20, and 4 were positive for CK7. In addition, all 20 of these tumors were positive for SATB2, and 19 were positive for CDX2. SATB2 appears to be a useful marker for the diagnosis of primary vs metastatic mucinous intestinal-type neoplasms and is highly sensitive in detecting lower gastrointestinal tract metastasis.