RESUMO
The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Arsenicais/efeitos adversos , Neoplasias da Mama/genética , Água Potável/efeitos adversos , Interação Gene-Ambiente , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Poluentes Químicos da Água/efeitos adversos , Adulto , Arsenicais/urina , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , México , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Poluentes Químicos da Água/urina , Proteínas de Sinalização YAPRESUMO
Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure.