Análise de associação dos genes CYP1A1,GSTM1,GSTT1,GSTT1 e da perda de heterozigose em 3p em portadores de carcinomas bucais /

Orientadora: Enilze M.S.F.RibeiroCo-orientadora: Ilce Mara de Syllos CólusInclui apêndiceTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Genética. Defesa: Curitiba, 2007Inclui bibliografia e anexosÁrea de concentração: Genétic

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: −0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation

SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study.

The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case-control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide < 6 ppm. SLC6A4 gene STin2 VNTR polymorphism was assessed using a Multiplex-PCR-based method. At baseline, participants were evaluated using the Fagerström Test for Nicotine Dependence (FTND) and the ASSIST scale

Análise de associação dos genes CYP1A1,GSTM1,GSTT1,GSTT1 e da perda de heterozigose em 3p em portadores de carcinomas bucais /

Orientadora: Enilze M.S.F.RibeiroCo-orientadora: Ilce Mara de Syllos CólusInclui apêndiceTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Genética. Defesa: Curitiba, 2007Inclui bibliografia e anexosÁrea de concentração: Genétic

FOXP3 Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01–3.66; p=0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p=0.019) and advanced TNM staging in TN (τ = 0.23; p=0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = −0.47; p=0.018) and lower histological grade (τ = 0.39; p=0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = −0.15; p=0.009) and higher Ki-67 (τ = 0.43; p=0.036) in HER2+ and advanced staging in TN (τ = 0.29; p=0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = −0.54; p=0.005) and staging (τ = −0.29; p=0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes

Glutathione S-transferase Mu (GSTM1) null genotype in relation to gender, age and smoking status in a healthy Brazilian population

The glutathione S-transferase mu (GSTM1) gene which acts during phase II of xenobiotic metabolism is polymorphic in the population, being absent in about 30-50% of individuals depending on the ethnic group from which they come. Epidemiological studies suggest that individuals who are homozygous null at the GSTM1 locus may have an increased risk of developing various types of neoplastic disease. We used the polymerase chain reaction (PCR) to estimate the frequency of GSTM1 in 176 healthy individuals from the north of Paraná (Brazilian state), the null genotype being detected in 48.86% of these individuals. The Student’s t-test was used to evaluate the frequency of the glutathione S-transferase null genotype in relation to age, gender and smoking habit and no significant differences were found. In our sample there were 142 individuals of Caucasian origin, of which 47.88% had the null genotype. When applied to the Caucasian group only (n = 142) the Student’s t-test again showed no significant differences between the frequency of the GSTM1 null genotype and age, gender and smoking habit

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2). FOXP3 (forkhead transcription factor 3) is a marker of regulatory T cells (Tregs), whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548) and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction). Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06) in relation to TNBC susceptibility. Most of the patients (83%) showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026). In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples