Riesgo de cáncer colorrectal asociado a medicamentos: estudio de casos y controles

Se realizo un estudio prospectivo de casos y controles de base hospitalaria para estimar el riesgo de padecer cancer colorrectal en funcion de diversos factores ambientales, entre los que se realizo un enfasis especial en la exposicion a medicamentos, y para explorar la posible interaccion de los factores ambientales entre si y con determinadas alteraciones geneticas. De un total de 436 casos de cancer colorrectal y 416 controles estudiados, 345 (79.13%) casos y 346 (83.17%) controles refirieron haber utilizado medicamentos con anterioridad a su ingreso y de forma continua durante 6 o mas meses. De estos 691 sujetos se recogieron datos sobre el uso de un total de 2547 medicamentos (1376 entre los casos y 1171 entre los controles). Se codificaron los medicamentos para describir la frecuencia de uso de los diversos tipos de farmacos y grupos terapeuticos. A partir de los datos se exploro la asociacion entre la presencia de cancer y el uso de los distintos tipos de farmacos, agrupados segun los niveles descritos, considerando la duracion y la secuencia temporal de la exposicion respecto al cancer, las caracteristicas clinicas y geneticas de los tumores y ajustando los riesgos por edad y sexo. Se observaron asociaciones significativas entre el uso cronico de laxantes, antianemicos e hipouricemiantes y un incremento de riesgo de cancer colorrectal, asi como asociaciones entre un menor riesgo de cancer colorrectal y el uso cronico de antiinflamatorios no esteroides, farmacos para el tratamiento de enfermedades cardiovasculares e insulina. Varias de las observaciones estudiadas sugieren mecanismos carcinogenicos comunes en los que de una forma u otra se implica la desregulacion de la insulina y/o la alteracion de factores de crecimiento relacionados con la insulina. La confluencia de varias observaciones en un mismo mecanismo probablemente esta reflejando que las principales causas de morbimortalidad en la cultura occidental son de origen ambiental y por lo tanto modificables en una gran proporcion. A prospective case-control hospital-based study was conducted to estimate the risk of colorectal cancer as a function of several enviromental factors, including drug exposure. An special attention was paid to drug use, and also to explore any interaction between drugs and enviromental factors and/or some genetical abnormalities. Overall, 436 colorectal cancer cases and 416 controls were studied, of which 345 cases (79.13%) and 346 controls (83.17%) referred the use of at least one medication continuously for at least 6 months prior to admission. Data on a total of 2547 exposures (1376 from case subjects and 1171 from control subjects) was collected from these 691 subjects. Medications were coded in order to describe frequencies of exposure to different drug types and therapeutic groups. The association between exposures and disease was explored to assess colorectal cancer risk, using drug exposure data, adjusting by age and sex, considering the lenght of the exposure and the temporal sequence with the cancer, as well as some clinical anf genetical features of the disease. Significant associations were observed suggesting an increased risk amongst chronic users of laxatives, of iron supplements and of treatments for hyperuricaemia, as well as reduced risk estimates for patients with chronic exposure to non-steroidal anti-inflammatory drugs, cardiovascular drugs and insulin. Several of the observed associations suggested common carcinogenic mechanisms involving to different degrees features of insulin disregulation and/or affecting insulin-related growth factors. Confluence of several observations into a common mechanism were probably reflecting that the main causes for morbimortality in occidental cultures can be attributed to enviromental factors, and thus could be potentially modifiable to a wide extent.