A pilot study on salivary HPV DNA detection to monitor active disease from patients with recurrent respiratory papillomatosis.

PURPOSE: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-related disease affecting the upper airway and saliva could be an important non-invasive sampling source for viral screening and clinical monitoring. We investigated whether HPV DNA could be detected in saliva (cellular pellets and supernatant) from RRP patients and influence on clinical manifestation of the disease. MATERIALS AND METHODS: In this pilot study, saliva samples from 14 RRP patients were obtained in preoperative condition (n = 7) and in disease-free interval (DFI; n = 7). Healthy donors (n = 14) were also included. HPV DNA was investigated by polymerase chain reaction (PCR)-based assays. RESULTS: From cellular pellets, HPV-positive saliva was only detected from preoperative collections (5/7; 71.4 %) and showed a mean cycle threshold (Ct) value of 24.33 (±1.25), whereas all patients in DFI were HPV-negative (Ct ≥ 32.16), revealing significant difference between these two clinical moments (p = 0.021). Patients in DFI and healthy donors showed similar Ct values. From saliva supernatant, detectable HPV cell-free DNA (cfDNA) occurred in 42.9 % (3/7) and 57.1 % (4/7) of preoperative collections using the commercial cfDNA kits from Norgen and Qiagen, respectively. Salivary cfDNA size distribution obtained by TapeStation analysis showed a predominant size range of 150 to 400 bp in both patients and healthy controls, corresponding to mononucleosomal and dinucleosomal fragments. CONCLUSIONS: In conclusion, HPV DNA screening in saliva (both cellular pellets and cfDNA) may have clinical utility to monitor active disease of RRP patients.

Nuclear and Cytoplasmic hTERT, Tumor-Infiltrating Lymphocytes, and Telomere Elongation Leukocytes Are Independent Factors in the Response to Neoadjuvant Treatment in HER2-Enriched Breast Cancer.

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.

The role of Calmodulin Binding Transcription Activator 1 (CAMTA1) gene and its putative genetic partners in the human nervous system.

The Calmodulin Binding Transcription Activator 1 (CAMTA1) gene plays a central role in the human nervous system. Here evidence-based perspectives on its clinical value for the screening of CAMTA1 malfunction is provided and argued that in future, patients suffering from brain tumours and/or neurological disorders could benefit from this diagnostic. In neuroblastomas as well as in low-grade gliomas, the influence of reduced expression of CAMTA1 results in opposite prognosis, probably because of different carcinogenic pathways in which CAMTA1 plays different roles, but the exact genetics bases remains unsolved. Rearrangements, mutations and variants of CAMTA1 were associated with human neurodegenerative disorders, while some CAMTA1 single nucleotide polymorphisms were associated with poorer memory in clinical cases and also amyotrophic lateral sclerosis. So far, the follow-up of patients with neurological diseases with alterations in CAMTA1 indicates that defects (expression, mutations, and rearrangements) in CAMTA1 alone are not sufficient to drive carcinogenesis. It is necessary to continue studying CAMTA1 rearrangements and expression in more cases than done by now. To understand the influence of CAMTA1 variants and their role in nervous system tumours and in several psychiatric disorders is currently a challenge.

Prevalence of Epstein-Barr virus infection in recurrent respiratory papillomatosis and the influence on disease severity.

Recurrent respiratory papillomatosis (RRP) is characterized by benign papillomatous lesions in the upper airway associated with human papillomavirus infection. It has been proposed that viral coinfections may contribute to an aggressive clinical course of the disease. For this purpose, we investigated the prevalence of Epstein-Barr virus (EBV) infection among 40 RRP patients by polymerase chain reaction assay. EBV DNA was detected in 11 cases and disease severity was observed in 54.5% of EBV-positive patients. No significant association was found between the RRP severity categories and EBV status (P > 0.05). Regardless EBV status, disease severity showed significant association with RRP diagnosis since childhood (P = 0.009). These findings indicate an absence of direct influence of EBV infection on aggressive course of RRP. However, the development of RRP since childhood increase the susceptibility to disease severity.

Genetic and methylation status of CDKN2A (p14ARF/p16INK4A) and TP53 genes in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare and chronic disease affecting the upper airway with papillomatous lesions caused by the human papillomavirus (HPV) infection, especially HPV-6 and/or HPV-11 types. Little is known about the genetic and epigenetic drivers in RRP pathophysiology. For this purpose, we analyzed 27 papillomatous lesions from patients with RRP to evaluate somatic mutations and methylation status in CDKN2A (p14ARF/p16INK4A) and TP53, which are key tumor suppressor genes for the cell cycle control. Sanger sequencing analysis revealed one somatic mutation in TP53 (c.733_734insA) and four mutations in CDKN2A (c.-30G > T, c.29_30insA, c.69delT, and c.300C > A). These mutations were observed in 10 patients, 6 of which carried double mutation. Furthermore, 50% (5/10) of these patients carrying somatic mutations had RRP severity, representing 62.5% (5/8) of the severity cases in this study, albeit no significant association was found between somatic mutations and disease severity. Methylation-specific polymerase chain reaction assays revealed p14ARF promoter hypermethylation in 100% of cases, followed by TP53 (96.3%) and p16INK4A (55.6%), suggesting the influence of HPV in the DNA methylation machinery. In conclusion, somatic mutations were not common events identified in patients with RRP. However, epigenetic modulation by high methylation rates, particularly for the p14ARF/TP53 pathway, seems to be in the course of RRP development.

The association of three DNA repair genes polymorphisms on the frequency of chromosomal alterations detected by fluorescence in situ hybridization.

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.

Hypermethylation in Gene Promoters Are Induced by Chronic Exposure to Benzene, Toluene, Ethylbenzene and Xylenes.

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.

Methylation profiling in promoter sequences of ATM and CDKN2A (p14ARF/p16INK4a ) genes in blood and cfDNA from women with impalpable breast lesions.

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.

Imunophenotypic Evaluation as a Tool for Monitoring Risks for Blood Malignancies in Gas Station Workers.

Background: Gas station workers are exposed to carcinogenic substances with impact on the hematologic and immune systems. The aim was to apply the immunophenotyping as a tool in the biological monitoring. Methods: This is a workplace-based case-control study with 49 workers and 26 controls. Medical interviews, hematological exams, and immunophenotyping analyses were performed. According to risk behavior (cleaning flannel and mistrust in the automatic fuel supply) the workers were divided into two groups: low risk (group 1) and high risk (group 2). Results: The results showed that CD16, HLA-DR, CD25, CD56+, CD16 CD56 low, and CD56 high expressions were higher in workers when compared to the control group (P =0.020, P =0.001, P =0.001; P =0.034, P=0.023, and P =0.008, respectively). The expressions of CD2, CD8, CD10, CD8low, and CD4/CD8 ratios were lower (P =0.016, P =0.001, P=0.001, P= 0.017, P = 0.0259, and P =0.029, respectively). Headache and paresthesia complaints were associated with workers when compared to the control group (OR = 4.091, 95% CI, 1.400 -11.951, P = 0.014; OR =12.12, 95% CI, 1.505 - 97.61, P =0.004). Using cleaning flannel and mistrust in the automatic fuel supply (risk behaviors) were associated with group 2 (OR = 9.71, 95% CI, 2.60-36.26, P = 0.005; OR = 18.18, 95% CI, 2.04-161.37, P = 0.004). Conclusions: The results strengthen the worker's immunosuppression hypothesis, which may contribute to some disorders and the carcinogenesis process. The evaluation of the immune system by flow cytometry is a promising tool for monitoring blood malignancy risk in addition to regular classic hematological exams.

Mutation profiling in the PIK3CA, TP53, and CDKN2A genes in circulating free DNA and impalpable breast lesions.

Breast impalpable lesions have become a clinical dilemma because they are small, presenting a heterogeneous cellular phenotype. The aim of this study was to evaluate the mutational profile of the PIK3CA, TP53, and CDKN2A genes, comparing the mammary tissue with the respective circulating free DNA (cfDNA). The PIK3CA, TP53, and CDKN2A genes were sequenced (PCR-Sanger) in 58 women with impalpable lesions (49 malignant and 9 benign) with the respective cfDNA. The chi-square or Fisher's exact test was used to evaluate statistical significance between the clinical variables and mutational profile. A total of 51 out of 58 samples generated successful mutation profiles in both breast lesion and cfDNA. Of the 37 mutations detected, 10 (27%) and 16 (43%) mutations were detected in benign and malignant breast lesions, respectively, while 2 (5%) and 9 (24%) were found in cfDNA of women with benign and malignant lesions, respectively. The lymph node involvement with mutations in the PIK3CA in malignant lesions (P = 0.001), and the relationship between mutations in PIK3CA, comparing ductal tumors with benign lesions (P = 0.05), were statistically significant. This study detected different mutations in PIK3CA, TP53, and CDKN2A genes, which represent, in part, the heterogeneity of impalpable lesions. The results confirm that more studies should be conducted on the functional role of cfDNA in the impalpable lesions.

Prevalence and clinical implications of low-risk human papillomavirus among patients with recurrent respiratory papillomatosis in Rio de Janeiro, Brazil.

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.

Low Levels of Vitamin D in a Cohort of Women with Impalpable Breast Lesions from Rio de Janeiro/Brazil

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.

Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case report

ABSTRACT CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.

Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case report.

CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.

Health survey and assessment of the polymorphisms BRCA1/P871L, BRCA1/Q356R, and BRCA2/N372H in female gas station workers in Rio de Janeiro.

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.

Screening of mutations in the additional sex combs like 1, transcriptional regulator, tumor protein p53, and KRAS proto-oncogene, GTPase/NRAS proto-oncogene, GTPase genes of patients with myelodysplastic syndrome.

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.

Experimental validation of the complement protein C3a down expression in the plasma of patients with squamous cell carcinoma of the penis.

OBJECTIVES: We have previously shown the importance of the complement system in differentiating between patients with squamous cell carcinoma of the penis (SCCP) and controls. These patients had low expression of C3a and C4 fragments. Therefore, in this study, we investigated the complement protein C3a as a potential circulating biomarker in these patients by a commercially available enzyme-linked immunosorbent assay (ELISA) test. PATIENTS AND METHODS: Plasma samples from 39 patients with SCCP, 15 patients with prostate cancer, and 50 healthy male subjects were evaluated using the ELISA-Bioscience OptEIA Kit human anti-C3a (BD). The nonparametric Mann-Whitney test was used for comparison of means among the groups. RESULTS: The complement protein C3a was found down expressed in patients with SCCP (P<0.05) in comparison to either subjects with good health or subjects with prostate cancer. CONCLUSION: Experimental validation of the down expression of C3a was well succeeded using a commercial ELISA kit. Complement system fragment C3a is down expressed in patients with SCCP. Besides, C3a is also low expressed in the plasma of patients with initial prostate cancer when compared to healthy subjects. These results suggest that the innate immune response might be suppressed in patients with these malignancies.

Association Between XRCC1 and WRN as Genetic Markers of Stability and Susceptibility to Cancer in Patients with HIV/AIDS and Cancer: a Cross-Sectional Study

Background: HIV-induced immunodeficiency has been implicated as a key factor for risk of cancer. Neoplasia is considered to result from accumulation of damage to the genome. Polymorphisms in repair genes, such as the XRCC1 and WRN, have been associated with susceptibility to development of cancer in patients with HIV/AIDS. The aim of this study was to analyze the frequency of polymorphisms in XRCC1 (Arg399Gln) and WRN (Cys1367Arg) in patients with HIV/AIDS with or without cancer. Materials and Methods: Genotyping for analysis of polymorphisms was carried out by PCR (Polymerase Chain Reaction) and RFLP (Restriction Fragment Length Polymorphism). Results: In the genotypic and allelic analysis, no increased risk of cancer was observed with any genotype or allele of XRCC1 (Arg399Gln) singly (prevalence ratio 2.82; p-value= 0.24). However, with the WRN (Cys1367Arg) gene, the heterozygous genotype and arginine allele were associated with increased risk (prevalence ratio= 25.62; p-value= 0.0001). Correlation analysis showed no association between gender and the risk (male p-value= 0.639 and women p-value> 1); however, a positive association for the increased risk of cancer was shown with XRCC1 (Arg399Arg) wild-type homozygous and WRN (Cys1367Arg) heterozygous (p-value< 0.001), with heterozygous XRCC1 (Arg399Gln) and WRN (Cys1367Arg) (p-value< 0.001), and with variant homozygous XRCC1 (Gln399Gln) and heterozygous WRN (Cys1367Arg) (p-value< 0.001). Conclusions: There is no increased risk of cancer in patients who are HIV/AIDS carriers of the XRCC1 (Arg399Gln) gene singly. However, there is a high risk in patients with HIV/AIDS who have the heterozygous genotype and the arginine allele in the WRN (Cys1367Arg) gene singly. Those with WRN (Cys1367Arg) heterozygote genotype showed a high risk of cancer with all genotypes of the XRCC1 (Arg399Gln) gene.

Benzene poisoning, clinical and blood abnormalities in two Brazilian female gas station attendants: two case reports.

BACKGROUND: Brazilian gas station workers are chronically exposed to benzene, toluene, xylene (BTX) during their working time. Describe below two cases of latin female gas station workers with benzene poisoning symptoms and miscarriage history. CASE PRESENTATION: In both cases were identified complex chromosomal rearrangements (CCR) with fluorescence in situ hybridization, applied to whole chromosome paints by chromosomes 1, 2 and 4. The lower natural killer cell (NK) cells have also been observed in cases correspondents, especially the rare type of NK (NKbright) in their peripheral blood cells. CONCLUSIONS: It is known that acquired chromosomal aberrations are positively correlated with cancer and reproductive risk. In concordance, lower NK cytotoxicity increases the risk for cancer, as well. Thus, this is the first study providing hints on a possible causative relation of lower NK cytotoxicity and increase rates of chromosomal rearrangements including CCRs.