499 Rev Méd Chile 2006; 134: 499-515 Farmacogenética del cáncer: Estudio de variaciones genéticamente determinadas en la susceptibilidad a cáncer por exposición a xenobióticos Luis Q uiñones 1a , Kuen Lee 1 , N elson Varela F 1b , M ario Escala 1 , Karen García 1c , Loreto Godoy 1c , Andrés Castro 1c , Jorge Soto 1d , Iván Saavedra 2e , D ante Cáceres 3f . Cancer pharmacogenetics: Study of genetically determined variations on cancer susceptibility due to xenobiotic exposure Pharmacogenetics is the study of genetically determined variations in the response to drugs and toxic agents, and their implications on disease. Recently, the discipline has acquired great relevancy due to the development of non-invasive molecular techniques that identify genetic variants in human beings. There is also a need to explain the individual differences in susceptibility to drug actions and disease risk. Genetic variants can modify the magnitude of a pharmacologic effect, toxicity threshold, secondary effects and drug interactions. There are approximately thirty families of drug-metabolizing enzymes with genetic variants that cause functional alterations and variations in pharmacologic activity. We summarize the general knowledge about genetic variants of biotransformation enzymes, their relationship with cancer risk and the role of ethnicity. Cancer pharmacogenetics is another promising and exciting research area that will explain why people with an almost identical group of genes, have a different susceptibility to cancer, whose etiology has genetic and environmental components (Rev Méd Chile 2006; 134: 499-515). ( Key words: Neoplastic processes; Pharmacogenetics; Toxicogenetics; Xenobiotics) Recibido el 24 de enero, 2005. Aceptado el 6 de septiembre, 2005. 1 Laboratorio de Carcinogénesis Química y Farmacogenética, Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 2 Laboratorio de Farmacocinética y Biodisponibilidad, Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile. 3 División de Epidemiología, Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Financiamiento: Proyecto FAI-MED-001-06 a Bioquímico, PhD b Tecnólogo Médico, MSc c Estudiante de Medicina d Bioquímico, Químico Farmacéutico e Químico Farmacéutico f Médico Veterinario MPH Correspondencia a: Luis Quiñones Sepúlveda. Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Uni- versidad de Chile. Apartado Postal 70.000, Santiago 7, Chile. Fono: (562) 6786376. Fax: 7372783. E mail: lquinone@med.uchile.cl A RTÍCULO DE R EVISIÓN