RESUMO
BACKGROUND/AIM: Many efforts have been made to identify candidate genes involved in cancer susceptibility. The present study aimed to investigate the association between Arg194Trp (XRCC1), Ala222Val (MTHFR) and Arg521Lys (EGFR) polymorphisms (SNPs) and their susceptibility to gastric and breast carcinoma cancer in patients from Brazilian Amazon, controlling population structure interference. MATERIALS AND METHODS: The SNPs were genotyped by TaqMan® SNP Genotyping Assays. Ancestry was estimated by analysis of a panel with 48 ancestry informative markers. RESULTS: Logistic regression analysis showed an inverse association with a 10% increase in African and European ancestry and cancer risk (odds ratio (OR)=1.919 and 0.676, respectively). In a preliminary Chi-square analysis a positive association between Arg521Lys (EGFR) polymorphism and carcinoma susceptibility was found (p=0.037); however, when two different methodologies to control population structure bias were utilized, this association was lost (p=0.064 and p=0.256). CONCLUSION: Genetic ancestry influence gastric and breast cancer risk and highlight the importance of population structure inference in association studies in highly admixed populations, such as those from Brazilian Amazon.
Assuntos
Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Genética Populacional , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias Gástricas/genética , População Negra , Brasil , Neoplasias da Mama/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Gástricas/patologia , População Branca , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVES: The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the effect of two gene polymorphisms, one in the CYP2B6 (rs3745274) gene and one in the CYP3A5 (rs776746) gene, on the development of hepatotoxicity in patients treated with anti-TB drugs in a Brazilian Amazon population. METHODS: TB patients who were treated with anti-TB drugs were examined for hepatotoxicity, an adverse effect that is characterized by liver damage. The genotype frequencies of the CYP2B6 and CYP3A5 genes examined in this study were assessed using RT-PCR. RESULTS: Thirty-one of the 220 subjects (14.1%) included in this study developed drug-induced hepatotoxicity. The result was significant when the TT homozygous mutant of the CYP2B6 gene was analyzed with additional key variables (p=0.046; odds ratio (OR) 0.063, 95% confidence interval (CI) 0.004-0.955), which may explain the hepatotoxicity results in this study. Using a univariate statistical model to associate the CYP3A5 gene A6986G polymorphism with the examined drugs, the results did not differ between samples from individuals with and without hepatotoxicity (p=0.176; OR 0.562, 95% CI 0.255-1.238). CONCLUSIONS: The G516T polymorphism in the CYP2B6 gene is a key predictor of the therapeutic response to treatment in TB patients.