Gene-environment analyses reveal novel genetic candidates with prenatal tobacco exposure in relation to risk for childhood acute lymphoblastic leukemia
Menée à l'aide de données de 2 études californiennes portant sur 2 765 témoins et 2 692 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë, cette étude analyse l'association entre une exposition maternelle au tabac pendant la grossesse et le risque de développer la maladie chez l'enfant et identifie ainsi de nouveaux gènes impliqués dans la leucémogenèse
Résumé en anglais
Background: Associations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California.
Methods: Maternal exposure to tobacco smoke was assessed with a validated methylation marker (cg05575921) of the aryl hydrocarbon receptor repressor (AHRR) gene in newborn dried blood spots. We adjusted for sex, birthweight, gestational age, mode of delivery, year of birth, AHRR quantitative trait locus (mQTL) rs77111113, and a polygenetic risk score for childhood ALL. We additionally adjusted for principal components in a gene-environment interaction testing method that incorporates gene-only and environment-only effects along with interactions.
Results: AHRR hypomethylation overall was not associated with childhood ALL. In gene-environment interaction testing, several genetic variants displayed significant interaction with AHRR hypomethylation and childhood ALL.
Conclusions: Our results suggest novel candidates in PTPRK and DPP6 may play a role in tobacco-related leukemogenesis. Further research is necessary to better understand the effects of tobacco and these variants on childhood ALL risk.
Impact: Despite lack of an overall “main effect,” tobacco exposure during pregnancy impacts childhood ALL risk depending on specific genetic variants.
