Diet Quality Influences the Occurrence of Food Aversions in Women Undergoing Adjuvant Chemotherapy for Breast Cancer.

Food aversions in women undergoing adjuvant chemotherapy for breast cancer may be linked to oxidative stress and gastrointestinal consequences underlying it, and diet possibly plays a role in this association. This follow-up study included 73 women with breast cancer treated in Florianopolis City, Brazil. Dietary antioxidant capacity-DaC (mmol/d), diet quality-Brazilian Healthy Eating Index Revised (BHEI-R score), and oxidative stress biomarkers were accessed before the treatment, and women were asked if they developed food aversions during adjuvant chemotherapy. Red meat was the main aversion-causing food reported (37.9%, n = 9). There was no difference in DaC, BHEI-R score, or oxidative stress biomarkers between women with no food aversion occurrence and those showing food aversions. A logistic regression adjusted model showed that women exhibiting higher BHEI-R scores were 1.08 times more likely to not develop food aversions during adjuvant chemotherapy (p = 0.041). In summary, this innovative investigation showed that diet quality before adjuvant chemotherapy may influence the non-occurrence of food aversion. Considering this, the result opens new areas for early nutritional interventions, focusing on reducing the occurrence of food aversions and consequently benefiting women with breast cancer by having better outcomes in oncologic treatment.

Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation.

Genetic testing for BRCA1, a DNA repair protein, can identify carriers of pathogenic variants associated with a substantially increased risk for breast and ovarian cancers. However, an association with increased risk is unclear for a large fraction of BRCA1 variants present in the human population. Most of these variants of uncertain clinical significance lead to amino acid changes in the BRCA1 protein. Functional assays are valuable tools to assess the potential pathogenicity of these variants. Here, we systematically probed the effects of substitutions in the C terminus of BRCA1: the N- and C-terminal borders of its tandem BRCT domain, the BRCT-[N-C] linker region, and the α1 and α'1 helices in BRCT-[N] and -[C]. Using a validated transcriptional assay based on a fusion of the GAL4 DNA-binding domain to the BRCA1 C terminus (amino acids 1396-1863), we assessed the functional impact of 99 missense variants of BRCA1. We include the data obtained for these 99 missense variants in a joint analysis to generate the likelihood of pathogenicity for 347 missense variants in BRCA1 using VarCall, a Bayesian integrative statistical model. The results from this analysis increase our understanding of BRCA1 regions less tolerant to changes, identify functional borders of structural domains, and predict the likelihood of pathogenicity for 98% of all BRCA1 missense variants in this region recorded in the population. This knowledge will be critical for improving risk assessment and clinical treatment of carriers of BRCA1 variants.

Telomere length in peripheral blood leukocytes and risk of renal cell carcinoma.

BACKGROUND: Telomeres are essential for chromosomal stability and may play a key role in carcinogenesis. Telomere length is suggested as a tentative biomarker of risk for renal cell carcinoma (RCC). However, results of previous association studies between telomere length and risk for RCC are inconsistent. METHODS: We evaluated RCC risk in relation to peripheral blood leukocyte telomere length using a hospital-based case-control study of 169 RCC cases and 189 controls. Cases were histologically-confirmed RCC patients who were treated at the Moffitt Cancer Center (Tampa, FL). Controls with no history of cancer underwent a screening exam at the Lifetime Cancer Screening Center at Moffitt Cancer Center to rule out the presence of cancer. Relative telomere length (RTL) was measured by quantitative real-time polymerase chain reaction (PCR) using peripheral blood leukocyte DNA. Logistic regression was used to determine the association between RTL and RCC risk. RESULTS: As expected, increasing age was inversely correlated with RTL (Pearson r=-0.213, P=0.003) among controls but not cases. Average RTL was significantly shorter in cases as compared with controls [mean ± standard deviation (SD): 3.18±1.50 and 4.39±1.99, respectively, P<0.001]. In contrast, average RTL was not significantly different by gender, race, smoking status among controls or by clinical stages among RCC cases. In regression analysis, we observed that shorter RTL is significantly associated with RCC risk [odds ratio (OR) =1.48; 95% confidence interval (CI): 1.27-1.71] after adjustment for covariates. CONCLUSIONS: We found that shorter RTL is associated with an increased risk for RCC. Our findings suggest that telomere length may be involved in the development of RCC.

miRNAs associated with prostate cancer risk and progression.

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate cancer. The discussion highlights key findings from previous studies, which reported the role of miRNAs in risk and progression of prostate cancer, providing an understanding of the influence of miRNA on prostate cancer. Our review indicates that somewhat consistent results exist between these studies and reports on several prostate cancer related miRNAs. Present promising candidates are miR-1, -21, 106b, 141, -145, -205, -221, and -375, which are the most frequently studied and seem to be the most promising for diagnosis and prognosis for prostate cancer. Nevertheless, the findings from previous studies suggest miRNAs may play an important role in the risk and progression of prostate cancer as promising biomarkers.

Profile development of noncommunicable chronic diseases in a Brazilian rural town.

OBJECTIVE: To assess the relationship between socioeconomic and anthropometric data, frequency of food consumption, and the development of noncommunicable diseases (NCDs) in patients from a small rural town in northeastern Brazil. METHODS: A cross-sectional questionnaire study was performed on patients from the Lagarto City Hospital (n = 50) and from family health units (n = 370). RESULTS: The 420 patients in the study had one or more NCDs such as hypertension, type 2 diabetes mellitus, and dyslipidemia. The mean age was 63.1 ± 8.7 years for both sexes. The typical patient was of mixed or black descent (66%), a farmer, and of low socioeconomic status and education; 100% of men and 84% of women were illiterate or had less than 4 years of schooling. Approximately 50% of women and 89% of men were married and most had never used tobacco or were ex-smokers. The body mass index (BMI) of the study population was 29.4 ± 5.5 kg/m(2), where 70% of the patients were type 2 diabetic with waist circumferences of 99.8 ± 21.2 cm for men and 98.1 ± 13.9 cm for women. The correlation between BMI and waist circumference was r = 0.88. Even with the use of medication, total cholesterol levels of above 240 mg/dL were recorded in 10% of women and about 5% of men. Likewise, 10% of women and 100% of men had triglyceride levels above 200 mg/dL; glucose levels were 133.6 ± 47.4 mg/dL in men and 110.8 ± 38.8 mg/dL in women. Blood pressure values were high, even in patients using one or more antihypertensive drugs for at least 2 years (systolic pressure = 128.5 ± 18.2; diastolic pressure = 86.3 ± 8.9 mmHg). Indices considered above the limit recommended by the World Health Organization (WHO) were obtained for 60% of women and 100% of men. Our research revealed that this population is characterized by a relatively low intake of fats and oils. Nevertheless, 100% of patients consumed meat every day, 57.6% never consumed processed foods such as candy or soft drinks, and 89% consumed coffee daily. Furthermore, the consumption of fruits was very low: 46.6% of respondents never ate fruit and 7.8% rarely consumed fruit. Likewise, 68.2% reported never eating milk and dairy products. Vegetables were consumed by only 51.4% of the population and 38.5% rarely or never consumed green vegetables. Products made from wheat, maize, cassava, beans, and rice were often consumed by 59.2% of the population. CONCLUSIONS: Our results indicate that the studied population is affected by nutritional transition, in which the greater access to carbohydrates and animal proteins is associated with high BMI, with the vast majority overweight and suffering from uncontrolled hypertension despite the use of medications. The high consumption of carbohydrates and animal protein, rapid urbanization, and sedentary lifestyle are the main factors responsible for the epidemic of noncommunicable diseases, especially among people with low income and education. Men are particularly affected, with increased visceral fat characterized by an increased waist circumference.

NAT2, XRCC1 and hOGG1 polymorphisms, cigarette smoking, alcohol consumption and risk of upper aerodigestive tract cancer.

AIM: To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer. PATIENTS AND METHODS: A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods. RESULTS: Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048). CONCLUSION: Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

Genetic interaction between NAT2, GSTM1, GSTT1, CYP2E1, and environmental factors is associated with adverse reactions to anti-tuberculosis drugs.

BACKGROUND: Adverse drug reactions (ADRs) associated with anti-tuberculosis (anti-TB) drug regimens have considerable impact on anti-TB treatment, potentially leading to unsuccessful outcomes. Nevertheless, the risk factors that play a role in anti-TB drug-induced ADRs are not well established. It is well documented that genetic polymorphisms in drug-metabolizing enzymes (DMEs) result in considerably complex variability in anti-TB drug disposition. In addition, the impact of pharmacogenetic variation on the metabolism of anti-TB drugs may be modifiable by environmental exposure. Thus, an assessment of pharmacogenetic variability combined with biomarkers of environmental exposure may be helpful for demonstrating the effect of the gene-environment interaction on susceptibility to ADRs induced by anti-TB drug therapy. OBJECTIVE: The aim of the study was to investigate the impact of the interaction between environmental risk factors and pharmacogenetic polymorphisms in four common DMEs--N-acetyltransferase 2 (arylamine N-acetyltransferase) [NAT2], glutathione S-transferase theta 1 [GSTT1], glutathione S-transferase mu 1 [GSTM1], and cytochrome P450 2E1 [CYP2E1]--on commonly reported ADRs to first-line anti-TB drugs in 129 patients receiving homogeneous TB treatment. METHODS: TB patients monitored during drug treatment were divided into subgroups according to the presence or absence of ADRs. Additionally, the patients' clinical and demographic characteristics were collected in order to identify the environmental factors that are potential triggers for ADRs induced by anti-TB drug treatment. Pharmacogenetic variability was determined by gene sequencing, TaqMan® assays, or polymerase chain reaction. RESULTS: The findings of this study suggest that the NAT2 slow acetylator haplotype, female sex, and smoking are important determinants of susceptibility to ADRs induced by anti-TB drugs. Patients carrying multiple, but not single, polymorphisms in the NAT2, GSTM1, GSTT1, and CYP2E1 genes were found to have an increased risk of ADRs, as revealed by gene-gene interaction analysis. Moreover, we also identified meaningful gene-environment interaction models that resulted in the highest levels of ADR risk. CONCLUSION: The study findings provide evidence of the clinical impact of the interaction between pharmacogenetic variability and environmental factors on ADRs induced by anti-TB drug therapy. Predictive pharmacogenetic testing and a comprehensive clinical history would therefore be helpful for identification and careful monitoring of patients at high risk of this complication.

Is the GSTM1 null polymorphism a risk factor in primary open angle glaucoma?

PURPOSE: To investigate the association of glutathione S-transferase (GST) GSTM1, GSTT1, and GSTP1 genes with the risk of primary open angle glaucoma (POAG) and clinical features of the disease. METHODS: We conducted a case-control study that included 87 Brazilian patients with POAG and 85 healthy controls matched for age, ethnicity, and sex, whose blood samples were genotyped for polymorphisms in GST genes using polymerase chain reaction (PCR) based methods. RESULTS: The GSTM1 null polymorphism was significantly more common in the POAG than in the controls group (OR: 2.1, 95% CI: 1.13-3.9; p=0.018). The combined GSTM1 null/GSTT1+ genotype and GSTM1 null/GSTP1 Ile/Val or Val/Val was more prevalent in POAG patients, being a risk factor for POAG (OR: 2.4, 95% CI: 1.16-4.9; p=0.016 and OR: 2.7, 95% CI: 1.07-6.74; p=0.033, respectively). The GSTM1 null/GSTT1+ genotype were associated with higher levels of IOP of both eyes and with more severe defect of the right eye optic nerve. The GSTM1 null/GSTP1 Ile/Val or Val/Val genotypes were associated with higher levels of IOP and more advanced defect of the right eye optic nerve and visual field. CONCLUSIONS: We demonstrate that GSTM1 null polymorphism is associated with POAG in the Brazilian population.

The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected.

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a "total ancestry" estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries--a phenomenon described and intended as the "whitening of Brazil"--is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.

Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations.

BACKGROUND: N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups. RESULTS: Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians. CONCLUSIONS: Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.

Glutathione S-transferases: an overview in cancer research.

IMPORTANCE OF THE FIELD: The Glutathione S-transferases (GSTs) have advanced beyond the classic view of their role in metabolism and are encouraging scientists to assess new approaches to cancer risk characterization and chemotherapy resistance and are opening up exciting possibilities in drug discovery. AREAS COVERED IN THIS REVIEW: In this review, the most recent knowledge about the impact of GST genetic polymorphisms in human's cancer susceptibility, ethnic differences in the effects of risk factors and the rise of the GSTs as important targets for drug development are presented. In this context, the ethnic distribution of GST alleles in different populations, which is an important concept that is being incorporated in epidemiologic studies of cancer risk and environmental exposure, was also evaluated. We present up-to-date information about the new generation of GST-activated cytotoxic prodrugs based on GST overexpression in tumor-acquired drug resistance and the newest results of clinical trials. WHAT THE READER WILL GAIN: A critical approach of the major advances in research of GST, underlining the new advances of GST genes polymorphisms in cancer susceptibility and target for therapeutic intervention. TAKE HOME MESSAGE: Although polygenic factors are involved in increased risk of cancer, the interindividual GST variability plays a central role in reduce cells exposure to carcinogens.

Glutathione s-transferase variants in a brazilian population.

Recent pharmacogenomic studies have revealed significant interethnic differences in glutathione S-transferase (GST) allelic frequencies among various ethnic groups. Therefore, we have investigated GSTM1 (gene deletion), GSTT1 (gene deletion) and GSTP1 (rs1695) polymorphism frequencies in 3 Brazilian ethnic groups (n = 203). GSTM1 and GSTT1 polymorphism analyses were performed by multiplex polymerase chain reaction, and GSTP1 (rs1695) analysis was done by polymerase chain reaction restriction fragment length polymorphism. GSTM1- polymorphism frequency was 33.2%, while GSTT1 null (GSTT1-) was 30.2%. The valine GSTP1*B (rs1695) allele was present in 35.1% subjects, while the heterozygous form (isoleucine/valine) was the most prevalent genotype (46.6%). We found a statistically significant difference in genotype frequency among Amerindians versus Caucasians (p = 0.016) and among Amerindians versus African-Americans (p = 0.033). Considerable frequency variation was found in our study, even when compared with other studies showing phylogeographical heterogeneity to the genes studied in Brazilian populations.

Uso de drogas por estudantes do ensino médio em Aracajú-SE / Drug use by high school students in Aracaju-SE

O objetivo deste artigo foi discutir o uso de drogas lícitas e ilícitas de forma eventual ou crônica por jovens estudantes do ensino médio de escolas públicas e particulares, considerando os aspectos econômicos e sociais. Para a obtenção dos dados foi aplicado um questionário e aos alunos foi garantidoo máximo de discrição e sigilo. Entre os entrevistados, cerca de 92% fazem uso freqüente de drogas, dasquais as mais utilizadas são as lícitas, representadas principalmente por álcool, consumido prioritariamente por 33,6% e tabaco por 22%. Entre as drogas ilícitas, as mais usadas são a maconha por 19%, cocaína 10% e crack 6%, além dos medicamentos anorexígenos e solventes por menos ou igual a1%. O uso de drogas entre homens e mulheres assumiu uma prevalência bastante similar, e o consumo mostrou-se maiorentre os indivíduos com atividade profissional remunerada.

The objective of this article is to discuss the use of licit and illicit drugs by eventual and chronic young users who go to high school in public and private institutions, evaluating their economic and social characteristics. A questionnaire was applied to students and discretion and secrecy were guaranteed. Among the participants, around 92% use drugs frequently. The most used drugs are the lawful ones,represented mainly by alcohol, consumed preferably by 33,6% and tobacco, 22%. Among the illicit drugs,the most used are the marijuana, 19%, cocaine, 10% and crack, 6%, and anorexigenic medicines and solvents smaller or equal to 1%. Drug use between men and women seem to have a very similar prevalence, being higher among individuals with a job.

Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry.

The report describes for the first time the enantioselective analysis of fluvastatin in plasma using LC-MS-MS. The enantiomers of fluvastatin (FV) were extracted from plasma with diisopropyl ether at pH 5.0. The enantiomers were separated on a ChiralCel OD-R column with a mobile phase consisting of a mixture of acetonitrile, methanol and water (24:36:40) containing 0.1% formic acid. The protonated ions and their respective product ions were monitored in two functions, 410.6>348.2 for FV enantiomers and 307.1>161.6 for the internal standard (warfarin). Recoveries were higher than 90% and the quantitation limit was 1.5 ng mL(-1) plasma for both enantiomers. The coefficients of variation and the relative errors obtained for the validation of the intra- and interassay precision and accuracy were less than 10%. The method was applied to the investigation of the enantioselective pharmacokinetics of FV administered in a single dose of 40 mg (Lescol, Novartis, São Paulo, SP, Brazil) to a patient with primary hypertension and hypercholesterolemia and genotyped as CYP2C9*1/*1. The data showed higher plasma concentrations of the (-)-3S,5R-fluvastatin enantiomer, with an AUC (-)/(+) of 1.84. Oral clearance values (CL/F) were 29.27 and 49.58 L/h, respectively, for the (-)-3S,5R- and (+)-3R,5S-fluvastatin enantiomers.

Efeito da fibra alimentar sobre os níveis de colesterol, HDL-Colesterol e Triaciglicerol Serico / Effect of the fiber ingestion over the cholesterol, HDL-Cholesterol and Triglyceride

Foi avaliado o efeito da fraçao fibra (pectina e lignina)e fonte de fibra (fibrax) em dietas ricas ou pobres em colesterol sobre os níveis séricos de colesterol, HDL-COL, e triacilglicerol de ratos. Foram aplicados 8 tipos de raçöes: 2 grupos controle (sem fibra, com ou sem a adiçao de 1g por cento de colesterol) e 6 grupos testes (com 5g por cento de lignina ou 5g por cento de pectina ou 10g por cento de fibrax, com ou sem adiçäo de 1g por cento de colesterol). O experimento foi realizado por 42 dias, utilizando 56 ratos. Ao final desse período, os ratos foram anestesiados e coletado o sangue por punçäo cardíaca. Pectina baixou o colesterol sérico, porém quando a dieta era rica em colesterol apresentou baixos níveis de HDL-COL. Lignina com colesterol dietético baixou o colesterol e HDL-COL sérico. Fibrax aumentou o colesterol sérico, porém baixou o triacilglicerol quando era adicionado colesterol dietético na raçäo. Dieta rica em colesterol, obteve menor nível de HDL-COL, em dietas isenta de fibra alimentar.