Abstract
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. Tobacco exposure during gestation has been investigated as a potential risk factor, but its role remains undefined. Given tobacco's toxicologic profile as a DNA-damaging agent, we examined the impact of DNA repair gene variability as a source of vulnerability to tobacco exposure risk for ALL. METHODS: Leveraging demographic and genotype data from two large California-based ALL epidemiology studies, we used logistic regression, MinimumP (minP) statistical method, and permutation tests to examine interactions between DNA repair genes and prenatal tobacco exposure. RESULTS: We found statistically significant interactions between prenatal tobacco exposure and DNA repair genes RECQL (minP = 1.00 × 10-4, FDR-P value = 1.86 × 10-2) and TDG (minP = 1.00 × 10-4, FDR-P value = 1.86 × 10-2) with regard to childhood ALL risk. Notable interactions in the homologous recombination pathway were observed among Latino children, whereas non-Latino White children displayed significant interactions in the base excision repair and nucleotide excision repair pathways. CONCLUSIONS: Our study highlights the significance of DNA repair genes and pathways when evaluating environmental exposure to tobacco smoke, suggesting that genetic variability within these pathways could impact vulnerability in the development of childhood ALL. IMPACT: This study highlights the significant impact of genetic variation interacting with prenatal tobacco exposure on ALL risk. Further research is needed to understand these interactions and their implications for ALL etiology. Expanding studies to other gene-environment interactions will aid in developing targeted prevention, diagnosis, and treatment strategies for pediatric oncology.