Examinando por Autor "Varela, N."

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    Ítem
    Farmacogenética, tabaco, alcohol y su efecto sobre el riesgo de desarrollar cáncer
    (Sociedad Chilena de Pediatria, 2018-08) Roco, Á.; Cerda, B.; Cayún, J.P.; Lavanderos, A.; Rubilar, J.C.; Cerro, R.; Acevedo, C.; Cáceres, D.; Varela, N.; Quiñones, L.A.
    Cancer is the second leading cause of death in the world, causing 8.8 million deaths in 2015 according to the World Health Organization (WHO). Risk factors for cancer include smoking and alcohol consumption. In Chile, 33.6% of the population and 21.2% of young people smokes. Alcohol consumption in the Chilean population is 74.5% and 12.2% in young people. Among the physiological factors that influence the development of cancer, the genetic factor plays a relevant role. It has been shown that the presence of genetic polymorphisms that alter the ability of the body to eliminate contaminants increase the risk of developing cancer. The same applies to polymorphisms that prevent DNA repair due to damage caused by environmental pollutants such as cigarette smoke. The objective of this review is to analyze the state of the art of the relationship between pharmacogenetics, smoking, and alcohol consumption as risk factors for the development of cancer. In conclusion, the results suggest that the presence of polymorphisms that alter the function of biotransformation enzymes phase I (CYP1A1, CYP1E1) and phase II (GST), as well as polymorphisms in DNA repair enzymes (ERCC1 / ERCC2), increase the risk of cancer induced by smoking and alcohol consumption. This association is important considering that smoking and drinking alcohol are highly prevalent among the Chilean population. © 2018, Sociedad Chilena de Pediatria. All rights reserved.
  • Miniatura
    Ítem
    Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica
    (Sociedad Médica de Santiago, 2017-04) Quiñones, L.; Roco, Á.; Cayún, J.P.; Escalante, P.; Miranda, C.; Varela, N.; Meneses, F.; Gallegos, B.; Zaruma-Torres, F.; Lares-Asseff, I.
    Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.
  • Miniatura
    Ítem
    Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: Comparison with caucasian and asian populations
    (Frontiers Media S.A., 2012-11) Roco, A.; Quiñones, L.; Agúndez, J.; García-Martín, E.; Squicciarini, V.; Miranda, C.; Garay, J.; Farfán, N.; Saavedra, I.; Cáceres, D.; Ibarra, C.; Varela, N.
    Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxic-ity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4* 17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5* 3(0.76) and CYP2C9* 3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(O.32), CYP1A2* 1F(0.77), CYP3A4* 1B(0.06), CYP2D6*2(0.4V, and MTHFRT(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19* 2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6* 4(0.04), CYP2C8*3(0.06), CYP2C9* 2(0.06), CYP2D6*4(0.12), CYP2EV5B(0.14), CYP2E1* 6(0.19), and UGT2B7* 2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range. © 2012 Roco, Quiñones, Agúndez, García-Martín, Squicciarini, Miranda, Garay, Farfán, Saavedra, Cáceres, Ibarra and Varela. © 2012 Roco, Quiñones, Agúndez, García-Martín, Squicciarini, Miranda, Garay, Farfán, Saavedra, Cáceres, Ibarra and Varela.