Drogas legales e ilegales y riesgo de neuroblastoma en la descendenciaestudio de casos y controles

Abstract

Introduction. Neuroblastoma is the most common extracranial solid tumor in childhood and the most common cancer diagnosed in the first year of life. Despite its importance, the etiology of neuroblastoma and many of the risk factors involved in its pathogenesis are still unknown. The objective of this research is to analyze the association between exposure to legal and illegal drugs during the different stages of pregnancy and the risk of neuroblastoma in the offspring. Methods. We carried out an observational study of individually matched cases and controls consisting of incident cases under 15 years of age diagnosed with neuroblastoma and control cases without the disease. All cases and controls resided in the Autonomous Community of the Region of Murcia and in other Autonomous Communities of Spain. Cases and controls were identified through the “Environment and Pediatric Cancer” hospital network and the minors without the disease were matched by date of birth, sex, ethnicity, and municipality of birth. The information was collected retrospectively between 2004 and 2014. Results. For these cases, we found that mothers 1) had two or more previous abortions, 2) they noticed later about their pregnancy, 3) they took more progestogens at the beginning of pregnancy and 4) they consumed less folic acid and/or vitamin supplements during the preconception stage and pregnancy than the mothers of the controls. Patients with the disease showed the following common patterns: 1) they presented a greater number of constitutional malformations/syndromes, 2) they were born before week 37 of gestation and by cesarean section, 3) they were exposed to a higher effective dose of ionizing radiation prior to diagnosis/interview; 4) they had a higher exposure to environmental tobacco smoke, cannabis and intrauterine alcohol; and 5) they were breastfed for fewer weeks with full breastfeeding than controls. The conditional logistic regression model showed an association of neuroblastoma development with maternal smoking (OR = 1.058; 95 % CI: 1.021-1.096) and with the effective dose of ionizing radiation from medical sources prior to the suspicion of the diagnosis (OR = 1.196; 95 % CI: 1.011-1.414), observing an increased risk from 20 millisievert received. A positive association was also found with any exposure to environmental cannabis smoke during pregnancy (OR = 4.108; 95 % CI: 1.212-13.921) and with the intake of hormonal treatment at the beginning of the gestational period (OR = 9.325; 95 % CI: 1,509-57,621). In the multivariate analysis, an inverse or protective association was also observed with the consumption of folic acid supplements during pregnancy (OR = 0.939; 95 % CI: 0.898-0.982) and the duration of full breastfeeding (OR = 0.952; CI 95 %: 0.907-0.998), observing the protective effect of the duration from the first 10 weeks of full breastfeeding. Conclusions. The results of study suggest that 1) the exposure to environmental tobacco and cannabis smoke during pregnancy, 2) exposure to hormonal treatments at the beginning of pregnancy, and 3) exposure of the child to ionizing radiation from medical tests prior to diagnosis, are environmental risk factors that could contribute to the development of neuroblastoma in the offspring. The duration of the consumption of folic acid supplements during pregnancy and full breastfeeding, could act as a preventive or protective factors associated with a lower risk of developing the disease.