Distinct Roles of Th17 and Th1 Cells in Inflammatory Responses Associated with the Presentation of Paucibacillary Leprosy and Leprosy Reactions.

It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4+ T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4+ IL-17A+ cells than those from LL patients. Higher concentrations of IL-17A and IL-1ß were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR+ ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.

Electrochemical behavior and corrosion resistance of Ti-15Mo alloy in naturally-aerated solutions, containing chloride and fluoride ions.

The electrochemical behavior and corrosion resistance of Ti-15Mo alloy to applications as biomaterials in solutions 0.15 mol L(-1) Ringer, 0.15 mol L(-1) Ringer plus 0.036 mol L(-1) NaF and 0.036 mol L(-1) NaF (containing 1,500 ppm of fluoride ions, F(-)) were investigated using open-circuit potential, cyclic voltammetry, and electrochemical impedance spectroscopy techniques, X-ray photoelectron spectroscopy and scanning electron microscope. Corrosion resistance and electrochemical stability of the Ti-15Mo alloy decreased in solutions containing F(-) ions. In all cases, there were formation and growth of TiO2 and MoO3 (a protector film), not being observed pitting corrosion, which might enable Ti-15Mo alloys to be used as biomedical implant, at least in the studied conditions, since the electrochemical stability and corrosion resistance of the passive films formed are necessary conditions for osseointegration.

High genetic differentiation of Aegla longirostri (Crustacea, Decapoda, Anomura) populations in southern Brazil revealed by multi-loci microsatellite analysis.

Species with a broad distribution rarely have the same genetic make-up throughout their entire range. In some cases, they may constitute a cryptic complex consisting of a few species, each with a narrow distribution, instead of a single-, widely distributed species. These differences can have profound impacts for biodiversity conservation planning. The genetic differentiation of four populations of Aegla longirostri, a freshwater crab found in two geographically isolated basins in Rio Grande do Sul State, Brazil, was investigated by analyzing pentanucleotide multi-loci microsatellites in a heteroduplex assay. Although no morphological differences were evident, we found significant genetic differentiation among the four populations, based on F(ST) values and clustering analysis. This high level of differentiation may be indicative of cryptic species in these populations. If this hypothesis is correct, then the species occurring in the Ibicuí-Mirim River, at the southern limit of the Atlantic Rain Forest, would be under threat, considering its very restricted distribution.

Relation between personality dimensions and symptomatology of depression in skin cancer patients.

BACKGROUND: Environmental psychological factors such as mood states can modify and trigger an organic response; depressive disorder is considered a risk factor for oncological development, leading to alterations both in the genesis and in the progression of the disease. Some authors have identified that personality relates to mood since a high score in neuroticism is associated with intense and long-lasting emotions of stress and therefore with the development of depressive behaviors. The objective of this study was to analyze the relationship between personality and depression in skin cancer patients. METHODS: A total of forty-seven clinically and histopathologically diagnosed patients were scheduled for an hour-long interview, during which they provided informed consent and sociodemographic information. The psychological questionnaires applied were the revised Eysenck Personality Questionnaire and the clinical questionnaire for the diagnosis of the depressive syndrome. RESULTS: The patient's mean age was 66.5 years (SD ± 12.4) and the majority were diagnosed with basal cell carcinoma (70.2%). The frequency of anxious/depressive symptoms was 42.5%, with an increase in depression scores in the female gender (p < 0.001). Furthermore, a difference was found in the neuroticism dimension related to gender, with higher values in women (p = 0.002). Depressive symptomatologic portraits were correlated with the dimensions of neuroticism (p < 0.001, r = 0.705), psychoticism (p = 0.003, r = 0.422) and lying (p = 0.028, r = - 0.321). CONCLUSIONS: Our results support the hypothesis that personality dimensions are related to the presence of anxiety/depressive symptomatology in patients with skin cancer, especially in the female gender. Highlighting the need for future research that delves into the implications at the psychological level, the quality of life, and the biological mechanisms that link personality and depressive symptoms in the development and evolution of skin cancer.

Transcriptome changes induced by docetaxel in human mammary cell lines expressing different levels of ERBB2.

The taxane docetaxel is currently the most effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. The mechanisms of docetaxel resistance are poorly understood. Overexpression of ERBB2 occurs in 15-30% of breast tumors and is associated with chemoresistance to a variety of anticancer drugs. In the present study, we sought to identify genes involved in ERBB2-mediated chemoresistance to docetaxel. We generated SAGE libraries from two human mammary cell lines expressing basal (HB4a) and high (C5.2) levels of ERBB2 before and after intensive exposure to docetaxel and identified potential ERBB2 target genes implicated in a variety of cellular processes including cell proliferation, cell adhesion, apoptosis and cytoskeleton organization. Comparison of the transcriptome of the cell lines before and after docetaxel exposure revealed substantially different expression patterns. Twenty-one differentially expressed genes between HB4a and C5.2 cell lines, before and after docetaxel treatment, were further analyzed by qPCR. The alterations in the expression patterns in HB4a and C5.2 cell lines in response to docetaxel treatment observed by SAGE analysis were confirmed by qPCR for the majority of the genes analyzed. Our study provides a comprehensive view of the expression changes induced in two human mammary cells expressing different levels of ERBB2 in response to docetaxel that could contribute to the elucidation of the mechanisms involved in ERBB2-mediated chemoresistance in breast cancer.

Protective effects of Hydrocotyle umbellata var. bonariensis Lam. (Araliaceae) on memory in sleep-impaired female mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hydrocotyle umbellata var.bonariensis Lam. (Hb), popularly known in Brazil as acariçoba and outside Brazil Hb by a number of names including marsh-pennywort, and many-flower, has traditionally been used in Ayurvedic medicine in the retardation of aging (Rasayana effect). AIM OF THE STUDY: The present study evaluated the effect of Hb treatment before and during paradoxical sleep deprivation (PSD) and sleep restriction (SR) on learning, memory, and acetylcholinesterase (AChE) brain activity. MATERIAL AND METHODS: Adult Swiss nulliparous female mice were randomly distributed among the experimental groups. The treated groups received the aqueous solution of Hb leaves orally at concentrations of 500 and 1.000 mg/kg. PSD and SR were induced by the multiple platform method, in which the animals remained for 3-days in PSD or 15-days in SR for 22 h per day. The collection of the vaginal epithelium occurred daily to determine the estrous cycle. Body mass gain was determined. The animals were submitted to the passive avoidance test and were then euthanized for the collection of brain tissue and the determination of cerebral cholinesterase activity. RESULTS: The aqueous solution of Hb was associated with a significant reduction in cholinesterase activity at both doses in the SR model, and at the dose of 1.000 mg/kg in the PSD model. Regarding the learning and memory test, the PSD group treated with 1.000 mg/kg presented significant improvement, whereas in the SR experiment none of the treated-groups showed any improvement in learning and memory. In the analysis of SR/PSD interference and/or Hb treatment on the estrous cycle, it was possible to observe that the treatment acted as a protector in the SR group, maintaining a normal cycle. CONCLUSIONS: The analyses showed that Hb was safe to use during periods of SR or PSD, acting as an adaptogen for these situations, in addition to being able to reduce cholinesterase activity, which suggests its neuroprotective action. In relation to the estrous cycle, Hb can act as a protector in SR situations.

Treatment of a child diagnosed with Niemann-Pick disease type C with miglustat: a case report in Brazil.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder that leads to variable symptoms that include cognitive decline, ataxia, dystonia, cataplexy, vertical supranuclear gaze palsy, and seizures. Currently, there is no specific treatment for NPC other than palliative care. Substrate reduction therapy represents a potential strategy for treating this debilitating neurodegenerative disorder. Miglustat (Zavesca) is a reversible inhibitor of the enzyme glucosylceramide synthase, which catalyses the first step in the biosynthesis of most glycosphingolipids. Miglustat has pharmacokinetic properties that allow it to cross the blood-brain barrier, thus making it a potential therapeutic agent for treating neurological symptoms in NPC patients. We present here a case report of a Brazilian child treated with miglustat. Before treatment, the patient presented with difficulties walking and swallowing, slurred speech, moderate cognitive impairments, ataxia, ptosis, and vertical supranuclear ophthalmoplegia. On a disability scale, the patient obtained a score of 15 before treatment and 8 after treatment. Following 12 months of treatment, the patient remained stable with improvements in speech, ptosis, ophthalmoplegia, ataxia, hypotonia and seizures. The Child Behavior Checklist (CBCL) was used to assess psychopathological, behavioural and social problems before and after treatment. The CBCL showed that indices for depression, affective and attention problems were all in the normal range following treatment. Thus, for this individual miglustat was an effective, well-tolerated and efficacious medication for treatment of NPC symptoms. Follow-up maintenance studies are vital to establish whether both the efficacy and safety of miglustat persist with time.

Toward an understanding of intermediate- and short-range defects in ZnO single crystals. A combined experimental and theoretical study.

A joint use of experimental and theoretical techniques allows us to understand the key role of intermediate- and short-range defects in the structural and electronic properties of ZnO single crystals obtained by means of both conventional hydrothermal and microwave-hydrothermal synthesis methods. X-ray diffraction, Raman spectra, photoluminescence, scanning electronic and transmission electron microscopies were used to characterize the thermal properties, crystalline and optical features of the obtained nano and microwires ZnO structures. In addition, these properties were further investigated by means of two periodic models, crystalline and disordered ZnO wurtzite structure, and first principles calculations based on density functional theory at the B3LYP level. The theoretical results indicate that the key factor controlling the electronic behavior can be associated with a symmetry breaking process, creating localized electronic levels above the valence band.

Radiosensitizer effect of usnic acid on Biomphalaria glabrata embryos.

PURPOSE: Some phytochemicals have shown the potential of being radiomodifiers, especially phenolic compounds, such as lichenic secondary metabolites. To evaluate the phytochemical usnic acid as a radiomodifier, embryonic cells of molluscs have been used due to their ease of collection, high sensitivity to physical and chemical agents, well-known embryology and low cost for analysis. MATERIALS AND METHODS: This study aimed to assess the radiosensitizing action of usnic acid on Biomphalaria glabrata embryos. Samples were irradiated with 4 Gy of gamma rays from a 60Co source (dose rate 2.906 Gy/h). An acute toxicity test was performed using B. glabrata embryos in the blastula stage, in order to determine the toxicity of usnic acid and to establish the lethal Concentration for 50% (LC50). Subsequently, the radiomodifing capacity of usnic acid was estimated using assays with B. glabrata embryos. RESULTS: Irradiation increased the number of non-viable embryos compared to unirradiated controls. Additionally, it was observed that embryos exposed to a non-toxic concentration of usnic acid (0.6 µg/mL) before irradiation showed a further enhancement in non-viable embryos when compared with exposure to ionizing radiation alone. CONCLUSION: The results presented here indicate that usnic acid makes cells more sensitive to the damaging effects of radiation.

Heavy metals in the bottom sediments of the Furo of Laura estuary, Eastern Amazon, Brazil.

The Furo of Laura is an economically important river in the Amazon estuary. Thus, in the present study, we evaluated the metal distribution (Al, Cd, Co, Cu, Cr, Fe, Ni, and Mg) in the bottom sediments of this river. The sediments were sampled at four points every 2months for a year with an Ekman-Birge sampler. After microwave acid digestion, the metal levels were determined by optical emission spectrometry with inductively coupled plasma. The particle size and organic matter content influenced the concentration of the metals. The sediments were not enriched by the analyzed metals; the estuary therefore retained the characteristics of an uncontaminated environment, thus serving as a reference environment for comparison.

Tuberculosis risks and socio-economic level: a case study of a city in the Brazilian south-east, 1998-2004.

OBJECTIVES: To explore tuberculosis (TB) risks in relation to potential determinants in the city of São José do Rio Preto, São Paulo State, Brazil; to analyse morbidity and mortality indicators in São José do Rio Preto, and to determine the relationship between the risk of TB and socio-economic level (SEL) using a geo-referenced information system (GIS) and the national census for 2000. METHOD: Standardised incidence rates and TB incidence and mortality rates were calculated. Socio-economic variables were determined using the statistical technique of principal component analysis. Data sources were the São Paulo State Data Analysis System (SEADE), the TB Notification Database (EPI-TB), the Information Department of the Brazilian Health Ministry (DATASUS), and the Brazilian Institute of Geography and Statistics (IBGE). New cases reported in 1998-1999 and 2003-2004 in the urban area of the city were geo-referenced and analysed. RESULTS: TB risk in the city is twice as high in areas of lower SEL than in areas with higher SEL. CONCLUSION: The identification of areas with different levels of risk enables the Municipal Health Department to propose innovative interventions to minimise the risk of disease at both individual and population level.

Identification of differentially expressed genes in prostatic epithelium in relation to androgen receptor CAG repeat length.

The CAG repeat within exon 1 of the androgen receptor (AR) has been associated with the development of prostate cancer. The shorter number of glutamine residues in the protein has been associated with a higher transcriptional activity of the AR and increased relative risk for prostate cancer. In an attempt to identify differentially expressed genes in prostate cancer in relation to AR CAG repeat length variation, in this study we used total mRNA from normal and tumor tissues from 2 prostate cancer patients with AR alleles containing 19 and 26 CAG repeats to perform differential-display RT-PCR analysis. We were able to identify 48 different transcripts that showed homology to several known genes associated with different biological pathways. Among the differentially expressed genes, ATRX and SFRP1 were further validated by quantitative RT-PCR. The transcripts of both ATRX and SFRP1 genes proved to be down-regulated in most of the prostate tumors analyzed by quantitative RT-PCR. Hypermethylation of the promoter region of the SFRP1 gene was found in 17.5% (7/40) of the cases analyzed and was associated with the loss of SFRP1 expression (p=0.014). The differentially expressed genes identified in this study are implicated in several cellular pathways that, when up- or down-regulated, might play a role in the tumorigenic process of the prostate.

Infrared reflectivity study of the phase transitions in sodium ammonium sulfate dihydrate.

This work reports a detailed infrared reflectivity investigation of the phase transitions in single crystals of sodium ammonium sulfate dihydrate (SASD). The polarized reflectivity spectra allow us to follow the temperature dependence of the polar vibrational modes and detect the critical behaviour of the vibrational parameters through the two low temperature structural phase transitions observed in the compound. The results obtained show that the mechanism of the transitions in SASD is complex, involving a strong coupling between pseudo-spins and phonons. In the paraelectric phase, the driving mechanism of the first phase transition (T(c1) = 95 K) appears to be related to a relaxation with a characteristic frequency that is much lower than the phonon frequencies. In the temperature range corresponding to the first ferroelectric phase (T(c1)>T>T(c2) = 79 K), the dynamics of the lattice change considerably and the parameters characterizing several vibrational modes display anomalous temperature dependences. The second phase transition occurring at T(c2) is marked by an important and discontinuous change of the spectral shape, indicating that a considerable lattice distortion is involved.

Detection of genetic polymorphism among and within Echinococcus granulosus strains by heteroduplex analysis of a microsatellite from the U1 snRNA genes.

Polymerase chain reaction of a pentanucleotide microsatellite in the U1 snRNA gene complex generated a multiple band pattern due to the priming of paralogous sequences. Denaturation and slow renaturation of polymerase chain reaction products allow the formation of heteroduplex DNA that can be detected by its differential mobility in polyacrylamide gel electrophoresis. Heteroduplex analysis was used to determine if the U1 snRNA microsatellite could be a useful genetic marker in Echinococcus granulosus. A U1 snRNA microsatellite fragment from E. granulosus was isolated and characterized by Southern blot and sequencing. Four E. granulosus strains were analyzed: sheep, Tasmanian sheep, cattle, and camel strains. The former two showed polymorphism and shared three of the six patterns found for sheep strain. The cattle strain displayed two patterns, and the camel strain was monomorphic. The electrophoretic profiles were used for statistical analysis in order to determine genetic distance and the relationship among strains. Heteroduplex analysis can be helpful in genotyping E. granulosus strains and is useful in detecting polymorphism within strains.

Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

Influence of sublingual captopril on plasma catecholamine levels during hypertensive emergencies and cold immersion.

Experimental evidence of captopril-induced inhibition of sympathetic activity, mediated by decrease in angiotensin II production, is presented. The blood pressure, plasma catecholamine, plasma renin activity, and plasma aldosterone responses to a single dose of sublingual captopril in 23 patients with hypertensive emergencies were evaluated. The major correlation found was between the captopril-induced decrease in blood pressure and the decrease in plasma norepinephrine levels (r = 0.57, p less than 0.01). In another 11 hypertensive patients with normal or high renin levels, captopril lowered by 65 percent the increase in plasma norepinephrine induced by cold immersion of the forearm. In both circumstances, plasma renin and aldosterone levels changed in accordance with the expected inhibition of angiotensin converting enzyme activity. These data suggest that, in selected circumstances in hypertensive patients, captopril exhibits a depressive influence on sympathetic activity along with the inhibition of the renin-angiotensin system.

Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To validate the use of the 36-item short-form questionnaire (SF-36) for measuring health-related quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: : Observational data at a single point in time. SETTING: : A specialized outpatient respiratory clinic. PARTICIPANTS: Thirty-four patients (mean +/- SE age, 58.29 +/- 1.87 years) with IPF and no significant comorbidity. A matched control group for HRQL measurements was composed of 34 normal subjects (mean age, 58.00 +/- 1.89 years). MEASUREMENTS AND RESULTS: Dyspnea was measured by the baseline dyspnea index (BDI). Respiratory function evaluation included FVC, FEV(1), and resting arterial blood gases. IPF patients showed a mean BDI score of 5.21 +/- 0.46. The mean FVC and FEV(1) values were 62.41 +/- 2.96% and 66.41 +/- 3.33%, respectively. The mean PaO(2) was 67 +/- 2.51 mm Hg, and the mean PaCO(2) was 37 +/- 1. 05 mm Hg. Patients scored significantly worse than control subjects with respect to the SF-36 domains of physical functioning, physical role, general health perceptions, vitality, social functioning, emotional role, and mental health index. BDI scores were significantly correlated with five SF-36 components, and FVC and FEV(1) were significantly correlated with two SF-36 components. Significant negative correlations were found between arterial pH and four SF-36 domains. CONCLUSIONS: Patients with IPF have a significant impairment of HRQL in both physical and psychological functioning. Dyspnea is the most important factor influencing the quality of life in these subjects. The SF-36 questionnaire is a valid instrument to evaluate HRQL in IPF patients.

Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion.

BACKGROUND: To better understand the pathogenesis of type 2 diabetes mellitus, insulin secretion and insulin sensitivity (IS) were evaluated in white Brazilians with impaired glucose tolerance (IGT), using the oral glucose tolerance test (OGTT) and the hyperglycemic clamp technique. METHODS: Twenty-five IGT subjects were individually matched with normal glucose-tolerant (NGT) subjects for demographic characteristics. At first, they were submitted to the OGTT and plasma glucose and insulin were measured. Of the 25 pairs, 20 could participate in the hyperglycemic clamp procedures, at a second visit. All participants had their plasma glucose levels equally increased to 180 mg/dl; this was maintained for three hours by variable glucose infusion. During the procedure, plasma glucose and insulin were measured at established intervals. RESULTS: In the postabsorptive state, the IGT subjects presented higher levels of plasma glucose, blood HbA1, and serum triglycerides, but similar plasma insulin levels. After the oral glucose load, early and total insulin release, in relation to glucose levels, were respectively, 43 and 67% lower in the IGT individuals. The index of whole-body IS was increased in the IGT individuals (4.36 +/- 1.71 vs 3.61 +/- 1.28 mg(-1). micro U(-1).100.ml2; p<0.05). By the hyperglycemic clamp technique first- (82 +/- 26 vs 215 +/- 88 micro U/ml; p<0.001) and second- (36 +/- 19 vs 73 +/- 44 micro U/ml; p<0.05) phases of insulin secretion was decreased in the IGT individuals, especially the first one. However, the groups did not differ in relation to the IS: IGT=13.52 +/- 7.27 and NGT=9.96 +/- 6.70 mg.ml/kg. micro U.min(-1); p > 0.05. Functional relationship of IS (y) on first-phase insulin release (x) showed a smaller (p<0.05) regression coefficient for the IGT group. CONCLUSION: Brazilians with IGT well-matched with NGT ones were characterized by impaired first- and second-phase insulin secretion (mainly the former), while defects in IS were not evident.

Granulocytes in the inflammatory process of BALB/c mice infected by Leishmania amazonensis. A quantitative approach.

We used previously immunized (partially resistant) and naive (highly susceptible) BALB/c mice infected with Leishmania amazonensis for evaluating the role of granulocytes in the course of murine leishmaniasis. The animals were examined at different times post-infection and granulocytes counted in lesion tissues examined ultra-structurally. Polymorphonuclear granulocytes predominated during the early phase of infection and their number decreased with progression of infection; their number was similar in both groups during the early and intermediate phases of infection, though slightly higher in immunized animals during the late phase. Eosinophils represented approximately 10% of cells in the inflammatory infiltrate, being higher during the intermediate phase, and not differing between the groups. Another approach was the evaluation of granulocyte migration to the peritoneal cavity of susceptible BALB/c mice or resistant C57BL/6 mice under several stimuli. There was no statistically significant difference between resistant and susceptible animals in any of the treatments. Despite the influx of granulocytes to the lesion and its possible role in the initial destruction of injected Leishmania, this aspect does not seem to have an important effect on the outcome of the leishmanial infection.

The CAG repeat polymorphism in the androgen receptor gene (AR) and its relationship to head and neck cancer.

Sex hormones may play an important role in the tumorigenic process of the head and neck. The aim of our work was to investigate whether the androgen receptor (AR) CAG repeat polymorphism is associated with an increased relative risk for head and neck cancer. Genomic DNA from 103 male patients with head and neck carcinomas and 100 male controls were analyzed for the AR CAG polymorphism by PCR amplification and direct sequencing or denaturing polyacrilamide gel electrophoresis. Logistic regression analysis showed a significant association between CAG repeat length and risk of head and neck cancer in individuals with more than 20 CAG repeats [OR=2.54 (95% CI, 1.3-4.8)]. For the group of individuals with oral and laryngeal cancer the estimated relative risk was increased to 2.79 (95% CI, 1.2-6.3) and 3.06 (95% CI, 1.0-9.6), respectively, in men with CAG repeat length >20. These results suggest, for the first time, that shorter AR CAG repeat alleles have a protective effect for head and neck cancer development.