ABSTRACT
OBJECTIVE: The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as well as to perform in silico assessments of the variants' potential impact. PATIENTS AND METHODS: We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR. RESULTS: The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs). CONCLUSIONS: The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.
Subject(s)
Breast Neoplasms , Superoxide Dismutase , Female , Humans , Breast Neoplasms/genetics , Breast Neoplasms/epidemiology , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Polymorphism, Single Nucleotide , Risk Factors , RNA, Circular , Superoxide Dismutase/genetics , Transcription Factors/geneticsABSTRACT
In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment. In mitochondria, a decrease of cytochrome c (cyt c) and proapoptotic protein release promotes cell survival and proliferation. The altered lipid metabolism also affects cardiolipin susceptibility to the peroxidation, a process involved in the dissociation of cyt c from mitochondrial inner membrane and its release, a key step of apoptosis. Therefore, UCPs by attenuating ROS generation and lipotoxicity may downregulate programmed cell death, a well-known physiological process controlling cell proliferation contributing to uncontrolled cell proliferation and tumorigenesis. In addition, tumor cells over-expressed UCPs, by inhibiting ROS generation acquire resistance to death during pharmacological treatment with oxidative stress drug inducers. Therefore, the aim of this review is to discuss recent findings regarding the role that UCPs play in cell survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote cell proliferation.
Subject(s)
Carcinogenesis/pathology , Cell Proliferation , Metabolic Diseases/physiopathology , Mitochondrial Uncoupling Proteins/metabolism , Neoplasms/physiopathology , Animals , Carcinogenesis/metabolism , HumansABSTRACT
Se analiza 1.552 casos atendidos en el Servicio de Urgencias de un hospital semi-urbano (Talagante) durante los meses de Mayo y Agosto de 1982.Los resultados muestran una tasa elevada de consultas pediatricas (47,8%); una utilizacion del Servicio por los beneficiarios legales de 62,2% y de personas sin ninguna prevision social 27,7%. Los consultantes mayores de 45 anos presentan un grado de analfabetismo que llega al 22%. El antecedente de haberse visto obligado a recurrir al Servicio de Urgencia a causa de negacion de asistencia en un policlinico es debil (1,6%). Por el contrario, el 50,7% habia acudido antes a este Servicio en el ano anterior. Las causas mas frecuentes son de origen respiratorio, seguidas en orden por las enfermedades infecciosas y los accidentes y violencias. Sobre el destino medico inmediato de estos consultantes, solo el 6,1% necesito ser hospitalizado, derivandolo hacia un Centro mas complejo, lo que es decidido por las causas y lugar de destino. Se deduce que existe por parte del publico una sobre-utilizacion del Servicio; que se justifica plenamente el uso de recursos humanos y materiales orientados hacia la solucion de urgencias pediatricas; y que los traslados de enfermos son habitualmente justificados con excepcion, en general, de los afectados por traumatismos
