Paternal Smoking Before Conception and During Pregnancy Is Associated With an Increased Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis of 17 Case-Control Studies.

Current evidence regarding the association between paternal smoking before conception or during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL) are inconsistent. We aimed to systematically summarize the current evidence regarding this potential association.Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE), we systematically retrieved PubMed, Embase, Web of Science, and Scopus, screened relevant literature, and assessed the methodological quality of the included studies. We calculated the pooled estimates using random-effects models. We assessed statistical heterogeneity by I values and χ tests for the Cochrane Q statistic. We further investigate the dose-response relation using 2-stage nonlinear models.A total of 17 case-control studies were identified, and the synthesized risk ratios (RRs) for smoking before conception (RR=1.15, 95% confidence interval: 1.04-1.27) and during pregnancy (RR=1.20, 95% confidence interval: 1.12-1.28) were both statistically significant. Moreover, the dose-response analysis showed a positive association as well.Current evidence from observational studies suggests the association between paternal smoking before conception or during pregnancy and the increased risk of childhood ALL, which needs to be confirmed in prospective studies.