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PURPOSE: Gas station workers (GSWs) are exposed to carcinogenic agents. The aim was to study the association of high somatic chromosome alterations (CAs) rates in the blood of GSWs and the polymorphisms of three genes playing a role in DNA double-strand break repair. METHODS: This is a cross-sectional study with 114 GSWs and 115 age-matched controls. Cytogenetic analyses, blood exams, medical interviews and genotypes for RAD51/G135C (rs1801320), ATM/P1054R (rs1800057) and CHEK2/T470C (rs17879961) genes were performed. RESULTS: The CA rate in GSWs was 9.8 CAs/1000 metaphases, and 19.1% of the workers had > 10 CAs per 1000 metaphases (group two). GSWs had decreased levels of monocytes (P = 0.024) in their blood exams. The number of variant alleles of the RAD51/G135C polymorphism was higher in GSWs (P = 0.011) compared to the controls, and were associated with enhanced number of CAs per worker (P = 0.008). No allele variant was found for CHEK2/T470C in this study. CONCLUSION: The RAD51/G135C polymorphism appears to be related to genome instability in gas station workers. Increasing the knowledge of DNA repair gene variations involved in maintaining genomic stability in GSWs may be crucial for future cancer prevention.
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Aberraciones Cromosómicas , Reparación del ADN/genética , Gasolina , Exposición Profesional , Recombinasa Rad51/genética , Adulto , Proteínas de la Ataxia Telangiectasia Mutada/genética , Brasil , Quinasa de Punto de Control 2/genética , Estudios Transversales , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Industria del Petróleo y Gas , Polimorfismo Genético , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Gas station attendants are occupationally exposed to benzene, toluene, ethylbenzene and xylene (BTEX) compounds and thus more susceptible to the biological effects of this mixture present in gasoline, especially due to the carcinogenicity of benzene. Furthermore, the harmful effects of BTEX exposure may be potentiated by genetic and epigenetic inactivation of critical genes. The objective was to evaluate such gene-BTEX interactions accessing the promoter methylation status of p14ARF, p16INK4A and GSTP1 in peripheral blood leukocyte samples. MATERIALS AND METHODS: The 59 exposed and 68 unexposed participants from Rio de Janeiro, Brazil, were included. The promoter methylation status was accessed by methylation-specific PCR (MSP) and GSTP1 Ile105Val polymorphism was investigated by PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: Both p14ARF and p16INK4A were significantly hypermethylated in exposed subjects compared to unexposed (p = 0.004 and p<0.001, respectively). Additionally, p16INK4A hypermethylation in the exposed group was correlated with chromosomal abnormalities (CAs) (p = 0.018), thus highlighting the influence of the gene-environment interactions on genome instability. Noteworthy, p16INK4A methylation was significantly associated with miscarriage among female attendants (p = 0.047), in which those who reported miscarriage exhibited hypermethylation in at least 2 of the 3 genes analyzed. The GSTP1 heterozygote genotype, which could affect the metabolism of benzene detoxification, was found in both groups but was more frequent in those occupationally exposed. No significant association was observed between GSTP1 genotypes and methylation status. CONCLUSION: Together, these findings indicate that gas station attendants with the aforementioned epigenetic and genetic profiles may be at greater risk of occupational BTEX exposure-induced genome instability, which could require concerted efforts to establish more preventive actions and constant biomonitoring in gas station attendants.
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Derivados del Benceno/efectos adversos , Metilación de ADN/efectos de los fármacos , Gasolina/efectos adversos , Regiones Promotoras Genéticas/efectos de los fármacos , Tolueno/efectos adversos , Xilenos/efectos adversos , Adulto , Brasil , Estudios de Casos y Controles , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Inestabilidad Genómica , Gutatión-S-Transferasa pi/genética , Humanos , Exposición por Inhalación/efectos adversos , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Salud Laboral , Polimorfismo Genético , Medición de Riesgo , Proteína p14ARF Supresora de Tumor/genéticaRESUMEN
The objective of the present study was to evaluate the epigenetic changes occurring in early stages of breast cancer. The present study investigated the methylation profile of the ATM, p14ARF and p16INK4a promoters in total blood and plasma cell-free DNA (cfDNA) from women with impalpable breast lesions compared with in total blood of a control cohort of women without breast lesions. The samples were evaluated using the methylation-specific PCR method. The Fisher's exact test was used to evaluate statistical significance between the methylation and clinical variables. A total of 111 women were evaluated, including 56 women with impalpable breast cancer (39/56 also had paired plasma cfDNA) and 55 women in the control cohort (55 blood DNA). For blood DNA from women with malignant impalpable breast lesions, p16INK4a exhibited the greatest percentage of methylation (48%), followed by ATM (37.5%) and p14ARF (27%) promoters, regardless of age variation. For plasma cfDNA, the methylation rates for ATM, p14ARF and p16INK4a were 26, 26 and 10%, respectively. The methylation rates for the blood DNA of controls were the lowest for ATM (9%), p14ARF (7%) and p16INK4a (7%). The women with impalpable breast lesions (benign and malignant lesions) exhibited the highest methylation rate, regardless of age, compared with the paired plasma cfDNA and controls. This epigenetic change was statistically significant for the promoters of ATM (P=0.009) and p16INK4a (P=0.001) (impalpable breast lesions vs. control). The present study demonstrated that epigenetic changes occurring in the ATM and CDKN2A genes detectable in liquid biopsy were associated with the development of impalpable breast lesions.
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OBJECTIVE: The aim of this study was to investigate the presence of human papillomavirus (HPV) in biopsy specimens from juvenile and adult patients with histopathological diagnosis of recurrent respiratory papillomatosis (RRP) treated in two public hospitals in Rio de Janeiro, Brazil. METHODS: We performed the detection and genotyping of HPV by PCR technique for the types 6, 11, 16, and 18 in biopsy specimens from 41 RRP patients. RESULTS: The juvenile onset RRP (JoRRP) corresponded to 61% and the adult onset RRP (AoRRP) corresponded to 39% of the study group. Prevalence of males was observed in both the adult (81.3%) and the juvenile (56%) groups. Lesions in the larynx were more frequent in the glottis (46%). Genotyping analysis only revealed patients with HPV-6 (34.1%), HPV-11(17.1%), and co-infection HPV-6 and -11 (48.8%). RRP severity was significantly associated with the JoRRP (p<0.001), with extralaryngeal disease and more surgeries. However, no significant association between RRP severity and HPV types was found. One co-infected patient in the JoRRP died due to the evolution of the disease with lung involvement. CONCLUSION: These results show the strong association of HPV-6 and/or HPV-11 types with RRP and could complement the diagnosis, prognosis, and therapies for these patients. In addition, the HPV vaccination should be encouraged to prevent the disease.
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Enfermedades de la Laringe/epidemiología , Enfermedades Pulmonares/epidemiología , Infecciones por Papillomavirus/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Enfermedades de la Tráquea/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Femenino , Genotipo , Papillomavirus Humano 11/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Papillomavirus Humano 6/genética , Humanos , Enfermedades de la Laringe/virología , Enfermedades Pulmonares/virología , Masculino , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Prevalencia , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Riesgo , Enfermedades de la Tráquea/virologíaRESUMEN
Background: Low levels of vitamin D have been described as a risk factor for the development of breast cancer. The aim of this study was to evaluate the serum levels of vitamin D (25OHD) in patients with impalpable breast lesions comparing with a control group. Methods: Vitamin D quantification (25OHD) was assessed in the plasma of 65 patients with impalpable breast lesions and from 20 health controls using a chemiluminescent microparticle immunoassay. Pearson's chi-square test and nonparametric t-Student were used to evaluate statistical significance between the clinical variables and the means of quantification of vitamin D. The receiver operating characteristic (ROC) curve was used to evaluate the correlation between age and vitamin sufficiency for the cases and the controls. Results: The prevalence of vitamin D deficiency and/or insufficiency in women with malignant lesions was 84% and 60% for the control group. Using the chi-square or Fisher's exact test, the relationship between vitamin D levels and age presented significant association only for the control group (P=0.002). Using ROC curve, the plot area (0.778) for the control group defined a cut-off value of 45 years to age, with specificity and sensitivity of 60% and 50%, respectively. Thus, the odds ratio for vitamin D insufficiency in women over 45 years was 1.37 (P=0.011). For the case group, clinical characteristics, histological grade, and lymph node involvement did not show any significant association. Conclusion: The prevalence of vitamin D deficiency/insufficiency is high in women with impalpable breast lesions, as well as in the control group, even in a tropical city. According to the results the age advancement may be involved with the decrease in vitamin D levels in plasma, but there was no statistical association between low levels of Vitamin D and breast cancer.
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Neoplasias de la Mama/complicaciones , Carcinoma Ductal de Mama/complicaciones , Carcinoma Intraductal no Infiltrante/complicaciones , Carcinoma Lobular/complicaciones , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Vitaminas/sangre , Adulto , Brasil/epidemiología , Neoplasias de la Mama/sangre , Carcinoma Ductal de Mama/sangre , Carcinoma Intraductal no Infiltrante/sangre , Carcinoma Lobular/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Prevalencia , Pronóstico , Factores de Riesgo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/etiologíaRESUMEN
Abstract Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.
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Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.
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Gas station workers are exposed to chemicals known to be carcinogenic, especially benzene. The objective was to analyze the health problems of female gas station workers by means of sociodemographic and clinical questionnaires, and laboratorial exams. We performed the genotyping of the polymorphisms BRCA1/P871L and BRCA1/Q356R by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, and of variant allele BRCA2/N372H through direct sequencing. The female workers showed a higher concentration of monocytes (P = 0.039); a greater number of spontaneous abortions (P = 0.025, OR = 4.977, 95% CI = 1.135-30.669); higher tobacco consumption (P = 0.013); and higher alcohol consumption (P = 0.05). The statistical analysis of the polymorphisms associated with the variables monocyte concentration and miscarriage number did not reveal a significant relationship, and smoking and spontaneous abortion were not statistically associated either. Environ. Mol. Mutagen. 58:730-734, 2017. © 2017 Wiley Periodicals, Inc.
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Alcanos/toxicidad , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Brasil , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Exposición Profesional , Polimorfismo de Nucleótido Simple , Uso de Tabaco/efectos adversosRESUMEN
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, different degrees of cellular dysplasia, and increased risk of progression to acute myeloid leukemia. International Prognostic Scoring System is the gold standard for MDS classification; however, patients exhibiting different clinical behaviors often coexist in the same group, indicating that the currently available scoring systems are insufficient. The genes that have recently been identified as mutated in MDS, including additional sex combs like 1, transcriptional regulator (ASXL1), tumor protein p53 (TP53), and KRAS proto-oncogene and GTPase (KRAS)/NRAS proto-oncogene, GTPase (NRAS), may contribute to a more comprehensive classification, as well as to the prognosis and progression of the disease. In the present study, the mutations in the ASXL1, TP53 and NRAS/KRAS genes in 50 patients were evaluated by sequencing genomic bone marrow DNA. Nine patients (18%) presented with at least one type of mutation. Mutations in TP53 were the most frequent in six patients (12%), followed by ASXL1 in two patients (4%) and NRAS in one patient (2%). The nine mutations were detected in patients with low- and high-risk MDS. The screening of mutations in MDS cases contributes to the application of personalized medicine.
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Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients.
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ADN Polimerasa beta/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Proteínas de Unión al ADN/genética , Recurrencia Local de Neoplasia/genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Anciano de 80 o más Años , Brasil , ADN Polimerasa beta/biosíntesis , Reparación del ADN/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Polimorfismo de Nucleótido Simple , Pronóstico , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
The use of vector surveillance tools for preventing dengue disease requires fine assessment of risk, in order to improve vector control activities. Nevertheless, the thresholds between vector detection and dengue fever occurrence are currently not well established. In Belo Horizonte (Minas Gerais, Brazil), dengue has been endemic for several years. From January 2007 to June 2008, the dengue vector Aedes (Stegomyia) aegypti was monitored by ovitrap, the sticky-trap MosquiTRAP™ and larval surveys in an study area in Belo Horizonte. Using a space-time scan for clusters detection implemented in SaTScan software, the vector presence recorded by the different monitoring methods was evaluated. Clusters of vectors and dengue fever were detected. It was verified that ovitrap and MosquiTRAP vector detection methods predicted dengue occurrence better than larval survey, both spatially and temporally. MosquiTRAP and ovitrap presented similar results of space-time intersections to dengue fever clusters. Nevertheless ovitrap clusters presented longer duration periods than MosquiTRAP ones, less acuratelly signalizing the dengue risk areas, since the detection of vector clusters during most of the study period was not necessarily correlated to dengue fever occurrence. It was verified that ovitrap clusters occurred more than 200 days (values ranged from 97.0±35.35 to 283.0±168.4 days) before dengue fever clusters, whereas MosquiTRAP clusters preceded dengue fever clusters by approximately 80 days (values ranged from 65.5±58.7 to 94.0±14. 3 days), the former showing to be more temporally precise. Thus, in the present cluster analysis study MosquiTRAP presented superior results for signaling dengue transmission risks both geographically and temporally. Since early detection is crucial for planning and deploying effective preventions, MosquiTRAP showed to be a reliable tool and this method provides groundwork for the development of even more precise tools.