Eny Maria Goloni-Bertollo

Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: A HuGE-GSEC review

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9–3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9–1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4–2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3–3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1–1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1–4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer.

Methylation as a biomarker for head and neck cancer

Head and neck cancer is a collective term that describes malignant tumors of the oral cavity, pharynx, and larynx characterized by high incidence and mortality rates. Although most HNSCC originate from the mucosal surface of the upper aerodigestive tract, where they can be easily detected during a routine clinical examination. Often the definitive diagnosis is delayed because of the difficulty in differentiating from other similar lesions. Activation of proto-oncogenes and inactivation of tumor suppressor genes are the major molecular alterations involved in carcinogenesis. In addition, epigenetic changes can alter the expression of critical genes important in the development of a variety of cancers. The detection of aberrant gene promoter methylation as a tool for the detection of tumors or its use as prognostic marker have been described for many different cancers including HNSCC. The search for biomarkers has as its main aim the evaluation and measurement of the status of normal and pathological biological processes as well as pharmacological responses to certain treatments. The tracking of these biomarkers is an important part for the identification of individuals in the early stages of head and neck cancer for its diagnostic and prognostic relevance reflecting in high survival rates, better quality of life and less cost to the healthcare system. Therefore, assuming that cancer results from genetic and epigenetic changes, analyzes based on gene methylation profile in combination with the pathological diagnosis would be useful in predicting the behavior of these head and neck tumors.

Iron deficiency anemia in children: a challenge for public health and for society

Iron deficiency anemia is the principal nutritional dearth in the world, and it especially affects children and pregnant women in developing countries. This paper presents a survey of the literature in this area, with the aim of providing a brief overview regarding the occurrence of iron deficiency anemia in Brazil. The article describes the etiology of the disease, the risk groups, the high prevalence of anemia in several areas of Brazil, and also the consequences of iron deficiency in children. The paper also shows some ways to control iron deficiency anemia and some intervention programs applied in Brazilian cities for curing and/or preventing this disease. The article concludes by emphasizing the need to establish strategies and treatments in our country that are based on a policy that brings together not only governmental administration but also all the community.

Head and neck cancer: causes, prevention and treatment

UNLABELLED Although head and neck carcinoma ranks fifth among cancer types, patient survival rates have not changed significantly over the past years. OBJECTIVE To determine the risk factors, causes, therapies, and prevention measures for head and neck cancer. METHOD Risk factors, causes, therapies, and preventive measures for this disease were searched on databases PUBMED, MEDLINE, and SCIELO. RESULTS Alcohol and tobacco are still atop risk factors. Other factors may influence the development of head and neck carcinoma. Surgery is the main treatment option, and the addition of radiotherapy following surgery is frequent for patients in the early stages of the disease. Other therapies target specific genetic molecular components connected to tumor development. Disease preventive measures include smoking cessation, limiting alcohol intake, preventing exposure to tobacco smoke and environmental carcinogenic agents, early detection of infection by HPV, maintaining oral health, good eating habits, and managing stress. CONCLUSION Additional research is needed for a more thorough understanding of the development of head and neck carcinomas and to shed light on new ways to improve therapeutic approaches and interventions.

LHX6 is a sensitive methylation marker in head and neck carcinomas

Head and neck cancer remains a morbid and often fatal disease and at the present time few effective molecular markers have been identified. The purpose of the present work was to identify new molecular markers for head and neck squamous cell carcinoma (HNSCC). We applied methylation-sensitive arbitrarily primed PCR (MS/AP-PCR) to isolate sequences differentially methylated in HNSCC. The most frequently hypermethylated fragment we found maps close to a cytosine guanine dinucleotide (CpG) island on chromosome 9q33.2, and hypermethylation of this CpG island was associated with transcriptional silencing of an alternative transcript of the LHX6 gene. Using combined bisulfite restriction analysis (COBRA), hypermethylation of this fragment was detected in 13 of 14 (92.8%) HNSCC cell lines studied and 21 of 32 (65.6%) primary tumors, whereas little or no methylation was seen in 10 normal oral mucosa samples. We extended this investigation to other cancer cell lines and methylation was found in those derived from colon, breast, leukemia and lung, and methylation was also found in 12/14 primary colon tumors. These findings suggest that differentially methylated (DIME)-6 hypermethylation is a good cancer marker in HNSCC as well as in other kinds of neoplasias and confirm the importance of searching for markers of epigenetic dysregulation in cancer.

Maternal risk for Down syndrome is modulated by genes involved in folate metabolism

Studies have shown that the maternal risk for Down syndrome (DS) may be modulated by alterations in folate metabolism. The aim of this study was to evaluate the influence of 12 genetic polymorphisms involved in folate metabolism on maternal risk for DS. In addition, we evaluated the impact of these polymorphisms on serum folate and plasma methylmalonic acid (MMA, an indicator of vitamin B12 status) concentrations. The polymorphisms transcobalamin II (TCN2) c.776C>G, betaine-homocysteine S-methyltransferase (BHMT) c.742A>G, methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) c.677 C>T and the MTHFR 677C-1298A-1317T haplotype modulate DS risk. The polymorphisms MTHFR c.677C>T and solute carrier family 19 (folate transporter), member 1 (SLC19A1) c.80 A>G modulate folate concentrations, whereas the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) c.66A>G polymorphism affects the MMA concentration. These results are consistent with the modulation of the maternal risk for DS by these polymorphisms.

Vascular endothelial growth factor genetic variability and coronary artery disease in Brazilian population

Atherosclerosis results from a complex interaction between environment and genetic risk factors. The gene encoding vascular endothelial growth factor (VEGF) is associated with differential protein expression and has been investigated in coronary artery disease (CAD) studies. Based on this, we aimed at determining if patients with CAD are affected by polymorphisms (−2 578, −1 154, and 936) in the VEGF gene, and also if these polymorphisms are associated with the number of diseased vessels and degree of arterial obstruction. The case group was formed by 175 Caucasian patients with angiographically confirmed CAD, and the control group involved 108 Caucasian patients with normal coronary angiograms. Polymerase chain reaction (PCR) was used for genotyping. Allele frequencies for VEGF −2 578A, −1 154A, and 936T were 0.46, 0.38, and 0.14 in cases and 0.49, 0.30, and 0.13 in control subjects. Allele and genotype distribution did not significantly differ between groups. A higher frequency of the VEGF −2 578AA genotype was observed in the group with three vessel disease (P = 0.008). No association between the VEGF −2 578, −1 154, and 936 polymorphisms and degree of arterial obstruction was observed. The frequency of carriers of two copies of the haplotype AG (−2 578/−1 154) were higher in the group with three-vessel disease (P = 0.05). In summary, our report shows that the VEGF −2 578 polymorphism has an influence on CAD severity, possibly because of a reduced VEGF expression, suggesting a protective effect of VEGF in atherosclerosis.

High frequencies of plexiform neurofibromas, mental retardation, learning difficulties, and scoliosis in Brazilian patients with neurofibromatosis type 1

A clinical study of Brazilian patients with neurofibromatosis type 1 (NF1) was performed in a multidisciplinary Neurofibromatosis Program called CEPAN (Center of Research and Service in Neurofibromatosis). Among 55 patients (60% females, 40% males) who met the NIH criteria for the diagnosis of NF1, 98% had more than six café-au-lait patches, 94.5% had axillary freckling, 45% had inguinal freckling, and 87.5% had Lisch nodules. Cutaneous neurofibromas were observed in 96%, and 40% presented plexiform neurofibromas. A positive family history of NF1 was found in 60%, and mental retardation occurred in 35%. Some degree of scoliosis was noted in 49%, 51% had macrocephaly, 40% had short stature, 76% had learning difficulties, and 2% had optic gliomas. Unexpectedly high frequencies of plexiform neurofibromas, mental retardation, learning difficulties, and scoliosis were observed, probably reflecting the detailed clinical analysis methods adopted by the Neurofibromatosis Program. These same patients were screened for mutations in the GAP-related domain/GRD (exons 20-27a) by single-strand conformation polymorphism. Four different mutations (Q1189X, 3525-3526delAA, E1356G, c.4111-1G>A) and four polymorphisms (c.3315-27G>A, V1146I, V1317A, c.4514+11C>G) were identified. These data were recently published.

A80G polymorphism of reduced folate carrier 1 (RFC1) and C776G polymorphism of transcobalamin 2 (TC2) genes in Down's syndrome etiology

CONTEXT AND OBJECTIVE There is evidence that polymorphisms of genes involved in folate metabolism may be associated with higher risk that mothers may bear a Downs syndrome (DS) child. This study therefore had the objective of investigating the A80G polymorphism of the reduced folate carrier 1 (RFC1) gene and the C776G polymorphism of the transcobalamin 2 (TC2) gene as maternal risk factors for DS among Brazilian women. DESIGN AND SETTING Analytical cross-sectional study with control group, at Faculdade de Medicina de São José do Rio Preto (Famerp). METHODS Sixty-seven mothers of DS individuals with free trisomy 21, and 113 control mothers, were studied. Molecular analysis of the polymorphisms was performed by means of the polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP), followed by electrophoresis on 2% agarose gel. RESULTS The frequencies of the polymorphic alleles were 0.51 and 0.52 for RFC1 80G, and 0.34 and 0.34 for TC2 776G, in the case and control groups, respectively. Thus, there were no differences between the groups in relation to either the allele or the genotype frequency, for both polymorphisms (P = 0.696 for RFC1 A80G; P = 0.166 for TC2 C776G; P = 0.268 for combined genotypes). CONCLUSION There was no evidence of any association between the RFC1 A80G and TC2 C776G polymorphisms and the maternal risk of DS in the sample evaluated.

Diffusion tensor MR imaging in neurofibromatosis type 1: expanding the knowledge of microstructural brain abnormalities

BackgroundNeurofibromatosis type 1 (NF1) is a hereditary disease with a dominant autosomal pattern. In children and adolescents, it is frequently associated with the appearance of T2-weighted hyperintensities in the brain’s white matter. MRI with diffusion tensor imaging (DTI) is used to detect white matter abnormalities by measuring fractional anisotropy (FA).ObjectiveThis study employed DTI to evaluate the relationship between FA patterns and the findings of T2 sequences, with the aim of improving our understanding of anatomical changes and microstructural brain abnormalities in individuals with NF1.Materials and methodsForty-four individuals with NF1 and 20 control subjects were evaluated. The comparative analysis of FA between NF1 and control groups was based on four predetermined anatomical regions of the brain hemispheres (basal ganglia, cerebellum, pons, thalamus) and related the presence or absence of T2-weighted hyperintensities in the brain, which are called unidentified bright objects (UBOs).ResultsThe FA values between the groups demonstrated statistically significant differences (P ≤ 0.05) for the cerebellum and thalamus in patients with NF1, independent of the occurrence of UBOs.ConclusionsDiffusion tensor MR imaging confirms the influence of UBOs in the decrease of FA values in this series of patients with NF1. Additionally, this technique allows the characterization of microstructural abnormalities even in some brain regions that appear normal in conventional MR sequences.