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Mouse mammary tumor virus (MMTV) is a retrovirus that has been associated with the development of breast cancer (BC) in mice. The identification of a 95% homologous gene sequence to MMTV in human BC samples has increased interest in this hypothesis. This virus in humans received the name of mouse mammary tumor virus-like (MMTV-like). Several cytokines may be involved in the interactions between MMTV and the immune system, such as interferon-gamma (IFN-γ), which can enhance Th1-mediated antitumor immune response but it can also play a protumorigenic role by transmitting antiapoptotic and proliferative signals. Little is known about the antiviral immune response in a microenvironment with the presence of MMTV-like in BC patients. Therefore, the purpose of the present study was to quantify the plasma levels of IFN-γ in the peripheral blood of 123 neoplasia-free donors and 98 BC patients of different molecular subtypes, by enzyme-linked immunosorbent assay (ELISA), and evaluate the association of these plasma levels with the detection of the MMTV-like env gene in tumor tissue. Correlation analyzes involving IFN-γ plasma levels and clinical-pathological parameters were performed by Kendall Tau-c test. In our study, a decrease in IFN-γ levels was observed in the group of BC patients (30.85 ± 57.49 pg/ml) compared to the control group (115.00 ± 176.80 pg/ml) (p < 0.0001). In the analysis by stratified BC molecular subtypes, Luminal-A (30.79 ± 61.04 pg/ml; p < 0.0001), Luminal-B (24.74 ± 25.78 pg/ml; p = 0.0188) and triple-negative (23.95 ± 40.45 pg/ml; p = 0.0005) had a lower plasma level compared to control group. There was no significant difference between IFN-γ plasma levels of MMTV-like DNA positive samples compared to MMTV-negative samples (p = 0.2056). In general BC, patients with larger tumor size had higher IFN-γ plasma levels (Tau-c = 0.202; p = 0.019). By analyzing the MMTV-like env negative samples, we could identify that IFN-γ plasma levels were higher in larger tumor size (Tau-c = 0.222; p = 0.020) and with greater lymph node involvement (Tau-c = 0.258; p = 0.042). Also, higher IFN-γ plasma levels were observed in patients with higher histopathological grades (Tau-c = 0.384; p = 0.019) in MMTV-like env positive samples. For the first time, we assessed the association between plasma levels of IFN-γ and the presence of the MMTV-like env gene in BC samples. However, more studies are needed to clarify whether the high levels of IFN-γ in MMTV-like env positive samples are reflecting a possible antiviral immune response or whether this cytokine is promoting tumor growth.
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Neoplasias de la Mama , Humanos , Animales , Ratones , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Virus del Tumor Mamario del Ratón/genética , Interferón gamma/genética , Genes env , Antivirales , Microambiente TumoralRESUMEN
The aim of this study was to determine the incidence of infections and cytological abnormalities and to investigate possible predisposing factors such as sociodemographic characteristics, sexual behavioral habits, and gynecological and obstetric backgrounds. Between 2013 and December 2016, a cross-sectional study was conducted among 429 consenting women, from whom cervical samples were tested for the presence of Human papillomavirus (HPV) by polymerase chain reaction (PCR). Susceptibility to HPV infection was assessed by binary logistic regression in light of possible predisposing factors, which were collected using a questionnaire. In our sample population, the prevalence of HPV infection was 49%; high-risk types had a higher prevalence of 89.1%. A larger proportion of HPV-infected women were under 25 years of age, were single, and had monthly incomes up to minimum wage. Multivariate binary logistic regression analysis showed that age younger than 25 years increased the odds of infection fivefold, while a monthly income of one to three minimum wages provided protection against HPV infection, even if the women were married or had a cohabiting partner. In the HPV-positive group, squamous intraepithelial lesions (SIL) occurred more frequently in women who earned up to one minimum wage monthly, but a monthly income of one to three minimum wages protected against the development of SIL. The results suggest that age, marital status, and monthly income are important cofactors for HPV infection and the development of SIL.
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PURPOSE: Every year, more than half a million women are diagnosed with cervical cancer (CC). Individual factors may contribute to the cervical cancer development, such as immunogenetic variation. CXCL12/CXCR4 axis is involved in tumor progression and aggressiveness. In the present study, we aimed to investigate a possible association between two single-nucleotide variants (CXCL12 rs1801157 and CXCR4 rs2228014) with HPV infection and cervical cancer development. METHODS: PCR technique was used to test HPV positivity in 424 women, in which the allelic frequency of CXCL12 rs1801157 and CXCR4 rs2228014 was also assessed by PCR-restriction fragment length polymorphism. RESULTS: CXCL12 rs1801157 was associated with HPV infection in the allelic distribution as well in the codominant, dominant and recessive genetic models; as well with squamous intraepithelial lesions (SIL) and CC in the codominant and dominant models. CXCR4 rs2228014 was associated to HPV infection in the codominant model and allelic distribution; as well with SIL/CC in the codominant, dominant and allelic models. Independent associations were found for CXCL12 AA genotype and HPV infection, SIL and CC development, as well as, CXCR4 allele T and HPV infection and CC. The variants interaction analysis demonstrated that the presence of both polymorphisms increases the susceptibility of HPV infection in 10.1 times, SIL (2 times) and CC development in 4.2 times. CONCLUSIONS: This is the first study demonstrating that the interaction of CXCL12 and CXCR4 variants contributes to the increased susceptibility of HPV infection, squamous intraepithelial lesions and cervical cancer development.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Alelos , Carcinogénesis/genética , Quimiocina CXCL12/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Receptores CXCR4/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
Human Papillomavirus (HPV) is the most frequent etiological agent sexually transmitted. In the context of the immune response, NF-kB pathway plays an important role controlling the expression of several genes essential to cellular activity and structural and/or functional changes in components of this pathway can promote the development of several tumors. Thus, the study purpose was to evaluate the influence of NFKB1 rs28362491 and NFKBIA rs696 genetic variants on HPV infection and cervical lesions development. In this study 334 patients were recruited, of whom 48.8% (n = 163) were HPV infected, and considered our case group. HPV-DNA was detected by polymerase chain reaction (PCR) and the genetic variants were assessed in blood cells and tumor tissues paraffin embedded samples through restriction fragment length polymorphism analysis. Among women who were recruited for this study who were infected, 37.4% presented precursor lesions and 16.8% were diagnosed with cervical cancer (CC). The present study did not observe significant effects of the interaction between such genetic variants on HPV infection, nor on the development of lesions and progression to CC. Further studies will be important to investigate if under some circumstance the NFKB1 rs28362491 and NFKBIA rs696 genetic variants influence the progression of HPV-associated lesions.
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Inhibidor NF-kappaB alfa/genética , Infecciones por Papillomavirus/patología , Adulto , Estudios de Cohortes , Estudios Transversales , ADN Viral/análisis , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Subunidad p50 de NF-kappa B/genética , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Polimorfismo de Nucleótido Simple , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/patologíaRESUMEN
Some of the more than 200 known HPV types are essential for cervical cancer development, the third type of cancer most incident in the female population. However, for the malignant transformation occur, some cofactors are needed, as the reactive oxygen species (ROS), which can be neutralized by the antioxidant system. The SOD2 enzyme, encoded by the same name gene, is found in mitochondria and is part of the first line of defense against oxidative stress damage. Genetic polymorphisms can act by altering the efficiency of the enzyme, among which the most studied is the rs4880. Thus, the purpose of the present study was to evaluate the association of this polymorphism with HPV infection and the development of low and high grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer, in 407 women attended by the public health system in Brazil. HPV detection in cervical secretion samples was carried out by polymerase chain reaction (PCR) and blood samples were used for polymorphism genotyping through PCR followed by restriction fragment length polymorphism (RFLP). PCR and restriction products were subjected to 10% polyacrylamide gel electrophoresis. HPV negative group (control) included 158 women and the HPV positive group (case) 249 women. The infected group was divided into No Lesion (n = 90), LSIL (n = 20), HSIL (n = 67) and cervical cancer (n = 72). The data found on socio-epidemiological characteristics and habits corroborated with data found in the literature. The distribution of genotypes in the control group was 51.9% women TC, 29.8% TT and 18.3% CC. In the case group, the distribution was 55.0% women TC, 26.1% TT and 18.9% CC. This is the first study evaluating the influence of SOD2 rs4880 polymorphism on HPV infection, the development of cervical intraepithelial lesions and cervical cancer in a Brazilian population, although additional studies are needed to corroborate the results.
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Biomarcadores de Tumor/genética , Polimorfismo de Nucleótido Simple , Lesiones Intraepiteliales Escamosas/genética , Superóxido Dismutasa/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adulto , Brasil , Estudios Transversales , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Fenotipo , Medición de Riesgo , Factores de Riesgo , Lesiones Intraepiteliales Escamosas/enzimología , Lesiones Intraepiteliales Escamosas/patología , Lesiones Intraepiteliales Escamosas/virología , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/enzimología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
This study aimed to verify the role of TGFB1 variants (c.-1638G>A, c.-1347C>T, c.29C>T, and c.74G>C) in HPV infection susceptibility and cervical lesions development, and their impact on TGFB1 cervical and plasma levels. TGFB1 genotypes were assessed with PCR-RFLP and haplotypes were inferred for 190 HPV-uninfected and 161 HPV-infected women. TGFB1 levels were determined with immunofluorimetric assay. Case-control analyses were performed with logistic regression adjusted for possible confounders. Women carrying -1347TT or -1347CT+TT as well as those with 29CT, 29CC, or 29CT+CC were more likely to have HPV than -1347CC and 29TT carriers, respectively. Regarding haplotypes, the most frequent were *4 (GCTG) and *3 (GTCG). Women *4/*4 were less likely to have HPV than those with no *4 copy. Comparing the inheritance of *3 and *4, carriers of *3/*4 or *3/*3 were more susceptible to HPV than *4/*4. The TGFB1 plasma and cervical levels were higher in the infected patients. Plasma levels were also higher in infected women with low-grade lesions. HPV-infected patients carrying *3/Other and *3/Other+*3/*3 presented lower TGFB1 plasma levels than those with no copy of *3. TGFB1 variants could contribute to the comprehension of the TGFB1 role in HPV-caused cervical disease.
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Infecciones por Papillomavirus , Humanos , Femenino , Haplotipos/genética , Infecciones por Papillomavirus/genética , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles , Polimorfismo de Nucleótido Simple , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: -0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation.
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BACKGROUND: Obesity is considered a chronic inflammatory disease and transforming growth factor beta 1 (TGFß1) might exert important roles in disease pathogenesis regulating adipocyte differentiation and immune-inflammatory environment. However, the role of this cytokine as a biomarker in obesity is poorly addressed. Therefore, the present study aimed to evaluate the impact of TGFB1 polymorphisms and TGFß1 plasmatic levels in obesity METHODS AND RESULTS: TGFB1 promoter region polymorphisms (rs1800468, G-800A and rs1800469, C-509 T) were evaluated in 75 obese patients and 45 eutrophic patients through PCR-RFLP and plasmatic TGFß1 was quantified through ELISA from 37 of the obese patients, and correlations with clinical and biochemical parameters were tested. Despite no association was found between TGFB1 polymorphisms and obesity susceptibility, several correlations with clinical data were noted. Among others, AC haplotype negatively correlated with plasmatic TGFß1, while plasmatic TGFß1 negatively correlated with C-reactive protein and positively correlated with liver abnormalities on ultrasound and, specifically, with steatosis presence and degree. Conversely, GT haplotype, which associates with higher TGFß1 production, was also positively correlated with the same parameters of liver abnormalities. Further, plasmatic vitamin D negatively correlated with TGFß1, while positively correlated with AC haplotype. CONCLUSION: Overall, the results indicate that TGFß1 might exert important roles in obesity pathophysiology and correlate with biochemical and clinical parameters both at systemic protein as well as at genetic level. Importantly, the consistent positive correlation at both levels with steatosis might suggest this cytokine as a biomarker for this hepatic abnormality in obese patients.
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Hígado Graso/sangre , Hígado Graso/complicaciones , Haplotipos , Obesidad/sangre , Obesidad/complicaciones , Factor de Crecimiento Transformador beta1/sangre , Factor de Crecimiento Transformador beta1/genética , Adolescente , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Hígado Graso/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Obesidad/genética , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Adulto JovenRESUMEN
Acute lymphoid leukemia (ALL) is a type of hematological neoplasm that affects the precursor cells of strains B, T and NK, with a higher incidence in the pediatric range. The pathophysiology of ALL is characterized by chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells. Despite the lack of information in the literature, it is believed that leukemogenesis originates from a complex interaction between environmental and genetic factors, which combined lead to cellular modifications. Environmental factors have been evaluated as possible predisposing factors in the development of ALL but there are still conflicting results in the world literature. In this context, the aim of the present review is to discuss the major exogenous factors regarding ALL.
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Carcinogénesis/inmunología , Regulación Leucémica de la Expresión Génica/inmunología , Interacción Gen-Ambiente , Células Progenitoras Linfoides/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Adulto , Linfocitos B/inmunología , Linfocitos B/patología , Carcinogénesis/genética , Carcinogénesis/patología , Diferenciación Celular , Proliferación Celular , Niño , Aberraciones Cromosómicas , Citocinas/genética , Citocinas/inmunología , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Células Progenitoras Linfoides/patología , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
Polymorphisms in the glutathione transferase enzymes (GSTs) genes have been associated with susceptibility to develop breast cancer (BC), but few are known regarding its role on this disease prognosis and impact on antioxidant status. This study evaluated the polymorphisms of GSTM1 and GSTT1 genes and their relationship with BC susceptibility and prognostic, as well as its impact on plasma reduced glutathione (GSH) levels. The present study included 121 women with invasive ductal BC and 151 healthy controls. Polymorphisms analyses were performed using the polymerase chain reaction (PCR) technique and GSH levels were measured with the Ellman's reagent. GSTT1 (OR 1.29; p = 0.39) and GSTM1 (OR 1.03; p = 0.91) polymorphisms did not show any association with BC susceptibility. The mean concentration values in nmol/L of GSH were 20.37 ± 5.82 for patients with null genotypes for both genes, 19.75 ± 3.47 for null GSTT1, 17.22 ± 1.35 for active GSTT1, 18.82 ± 1.96 for absent GSTM1, and 16.59 ± 1.66 for active GSTM1, but no significance was found. Therefore, it can be concluded that the behavior of these polymorphisms concerning BC might be not only related to the absence of enzymatic expression but may also be related to the body's response with its antioxidant mechanisms and it should be further studied.
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Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Adulto , Anciano , Antioxidantes/metabolismo , Brasil/epidemiología , Neoplasias de la Mama/sangre , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Femenino , Estudios de Asociación Genética , Glutatión/sangre , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , PronósticoRESUMEN
Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.
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Background: The increase in breast cancer (BC) cases in young women is of great importance since the tumor behavior in this group is generally more aggressive than in their older counterparts, and strategies for early diagnosis and prognostication are needed. Therefore, this work sought to investigate prognostic markers associated with young (<44 years old) BC patients. Methods: Two hundred thirty-six primary tumor tissues from 232 BC patients, of which 44 had less than 44 years at diagnosis were evaluated regarding the expression of estrogen and progesterone receptors (ER and PR), human epidermal growth factor receptor 2 (HER2), Ki67, and p53 (used as an indicator of p53 mutations) through immunohistochemistry. Also, data regarding tumor size, histopathological grade (HG), lymph node metastasis disease stage, and patients' survival status were collected. Results: Early age tumors had higher Ki67 expression and p53 mutations, and these markers were positively correlated with each other and associated worse prognosis parameters, such as negativity for ER and PR and positivity for HER2, and with higher HG, tumor size, and disease stage. In young patients, Ki67 correlated with ER, PR, and HG, whereas p53 correlated with HER2 and disease stage. Also, Ki67 associated with BC death independently of time from diagnosis, patients age, tumor size, and disease stage, and showed a trend toward a positive correlation with death in young patients, but not in the older group. Conclusion: Young BC patients were more likely to have intensely proliferative tumors with p53 mutations and these markers may hold prognostic relevance in BC, especially in this subgroup of patients.
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Neoplasias de la Mama , Proteína p53 Supresora de Tumor , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Femenino , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Regulatory T cell (Treg) lineage plays a central role in inflammation and autoimmunity control. Interleukin-10 (IL-10) has been described as a pleiotropic cytokine that is mainly released by CD4+ CD25+ FOXP3+ Treg cells and has a potent immunosuppressive activity. Forkhead box P3 (FOXP3) transcription factor expression is crucial for Treg to function as a suppressor cell, and FOXP3 gene single nucleotide variants (SNVs) have already been shown to influence on viral pathogenesis. This study was conducted to evaluate the plasmatic and cervical levels of IL-10 in human papillomavirus-infected and uninfected patients and investigate whether the FOXP3 intron -1 SNVs rs3761548 and rs2232365 might alter IL-10 secretion. SNVs were genotyped by the characterization of polymerase chain reaction (PCR) products based on sequence-specific enzymatic cleavage using restriction fragment length polymorphism (RFLP) method. IL-10 levels were determined by quantitative enzyme-linked immunosorbent assay (ELISA). In conclusion, the data indicate that there is no association between FOXP3 SNVs and circulating and cervical IL-10 levels. This finding provides a rationale that IL-10 gene activation is independent of FOXP3 transcription factor activities on Treg cells.
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Factores de Transcripción Forkhead/genética , Interleucina-10/análisis , Interleucina-10/sangre , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Femenino , Factores de Transcripción Forkhead/clasificación , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Linfocitos T Reguladores/inmunologíaRESUMEN
Breast cancer (BC) is a heterogeneous and multifactorial disease. The system formed by glutathione-S-transferases (GSTs) acts to protect the organism against the oxidative stress generated by xenobiotics and their active products. Glutathione transferase mu 1 (GSTM1) and glutathione transferase theta 1 (GSTT1) present null polymorphic variants by complete deletion. The absence of these enzymes may influence the susceptibility to several diseases such as BC. This study aimed to systematically review and investigate the existence of a possible correlation between the presence/absence of these genetic variants and the development of BC and their influence in chemotherapy response. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used, and the searches were performed in the portal of the Virtual Health Library (VHL) and the PubMed, resulting in 21 articles. It is clear that most studies revealed a risk association between the deletion of GSTM1 and/or GSTT1 and the development and/or prognosis of BC.Moreover, it should be noted that these results of risk association were found in large part in the populations of the Americas and Europe, followed by Asians. Regarding the response to treatment, protective associations were found in the presence of GSTM1 deletion. However, due to the inconclusive results of many studies, further analysis in this area is required.
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Neoplasias de la Mama/genética , Glutatión Transferasa/genética , Biomarcadores Farmacológicos , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/metabolismo , Humanos , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Factores de RiesgoRESUMEN
PURPOSE: Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer. METHODS: Genomic DNA was extracted from patient's peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire. RESULTS: Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI95% 1.02-4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI95% 1.05-4.47). CONCLUSION: Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.
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Interleucina-10/genética , Neoplasias del Cuello Uterino/genética , Adenocarcinoma/sangre , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Adulto , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Estudios de Casos y Controles , ADN/sangre , ADN/genética , Femenino , Genotipo , Humanos , Interleucina-10/biosíntesis , Interleucina-10/inmunología , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/inmunologíaRESUMEN
PURPOSE: APOBEC3A and APOBEC3B cytidine deaminases have been implicated in the pathogenesis of multiple cancers, including breast cancer (BC). A germline deletion linking APOBEC3A and APOBEC3B loci (A3A/B) has been associated with higher APOBEC-mediated mutational burden, but its association with BC risk have been controversial. Therefore, this study investigated the association between A3A/B and BC susceptibility and clinical presentation in a Brazilian cohort. METHODS: A3A/B deletion was evaluated through allele-specific PCR in 341 BC patients and 397 women without familial or personal history of neoplasia from Brazil and associations with susceptibility to BC subtypes were tested through age-adjusted logistic models while correlations with clinicopathological parameters were tested using Kendall's tests. RESULTS: No association was found between A3A/B and BC susceptibility; however, in Luminal-A BCs, it was positively correlated with tumor size (Tau-c = 0.125) and Ki67 (Tau-c = 0.116) and negatively correlated with lymph node metastasis (LNM) (Tau-c = - 0.162). The negative association between A3A/B with LNM in Luminal-A BCs remained significant even after adjusting for tumor size and Ki67 in logistic models (OR = 0.22; p = 0.008). CONCLUSION: These results show that although A3A/B may not modify BC susceptibility in Brazilian population, it may affect clinicopathological features in BC subtypes, promoting tumor cell proliferation while being negatively associated with LNM in Luminal-A BCs.
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Neoplasias de la Mama/genética , Citidina Desaminasa/genética , Eliminación de Gen , Mutación de Línea Germinal , Antígenos de Histocompatibilidad Menor/genética , Adulto , Anciano , Brasil , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Transforming growth factor beta 1 (TGFß1) is a pleiotropic cytokine that acts in a context-dependent manner. In breast cancer (BC) this cytokine exerts subtype- and stage-specific roles, inhibiting poorly aggressive tumors while enhances the invasive potential of highly aggressive cancers. Single-nucleotide polymorphisms (SNPs) affecting TGFß1 production largely reflect this pattern of association, but studies investigating systemic TGFß1 levels in BC patients and their association with clinical features or SNPs produced conflicting conclusions. Therefore, the present work investigated plasmatic TGFß1 levels through enzyme linked immunosorbent assay (ELISA) in 341 individuals previously genotyped for four TGFB1 SNPs [G-800A (rs1800468), C-509T (rs1800469), T29C (rs1800470) and G74C (rs1800471)], encompassing 184 neoplasia-free women with clinical information regarding health status, 113 treatment-free pre-surgery BC patients and 44 treated BC patients. Results have shown that TGFß1 levels varied greatly in function of health status in neoplasia-free women, and disease-free individuals had higher TGFß1 levels than both treatment-free or treated BC patients. There was no correlation between TGFß1 with clinicopathological features in treatment-free BC general group, but it was negatively correlated with tumor size in luminal-B-HER2+ patients and with histopathological grade in triple-negative group. Also, TGFB1 ACTG haplotype (from G-800A to G74C) was associated with decreased TGFß1 levels compared to the reference GCTG haplotype, and regression analyses showed that this association was independent of age, health status or BC diagnosis. In conclusion, several factors may influence TGFß1 levels, and ACTG haplotype seems to be an important factor regulating TGFß1 production.
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Neuroblastoma (NB) is a heterogeneous and particularly malignant childhood neoplasm in its higher stages, prone to form metastasis in selected organs and for which there is still no efficient treatment available beyond surgery. Evidence indicates that chemokines and their receptors present involvement as mediators of neuroinflammation and have a neurophysiological role. In the present study, we aimed to verify if CCR5 (rs333) and CXCL12 (rs1801157) allelic variants were associated with NB. For CCR5 (rs333) D32 carriers (OR: 5.96, IC: 2.21-16.06) and for CXCL12 genotype 3'A/3'A (OR:26.18, IC:6.15-111.4) there were statistically significant differences as well to allelic frequency (OR:4.20, IC: 2.19-8.03). Although no correlation was verified regarding prognostic parameters for both CCR5 and CXCL12 polymorphic variants, these polymorphisms may be associated with NB susceptibility which deserve attention for future investigations.
RESUMEN
Weight gain is a metabolic disorder that often culminates in the development of obesity and other comorbidities such as diabetes. Obesity is characterized by the development of a chronic, subclinical systemic inflammation, and is regarded as a remarkably important factor that contributes to the development of such comorbidities. Therefore, laboratory methods that allow the identification of subjects at higher risk for severe weight-associated morbidity are of utter importance, considering the health, and safety of populations. This contribution analyzed the plasma of 180 Brazilian individuals, equally divided into a eutrophic control group and case group, to assess the presence of biomarkers related to weight gain, aiming at characterizing the phenotype of this population. Samples were analyzed by mass spectrometry and most discriminant features were determined by a machine learning approach using Random Forest algorithm. Five biomarkers related to the pathogenesis and chronicity of inflammation in weight gain were identified. Two metabolites of arachidonic acid were upregulated in the case group, indicating the presence of inflammation, as well as two other molecules related to dysfunctions in the cycle of nitric oxide (NO) and increase in superoxide production. Finally, a fifth case group marker observed in this study may indicate the trigger for diabetes in overweight and obesity individuals. The use of mass spectrometry combined with machine learning analyses to prospect and characterize biomarkers associated with weight gain will pave the way for elucidating potential therapeutic and prognostic targets.