TOBACCO SMOKE AND RISK OF CHILDHOOD LEUKAEMIA: FINDINGS FROM THE SETIL CASE-CONTROL STUDY

Introduction. Tobacco smoke could cause childhood leukaemia through at least two different pathways: 1) prenatal parental smoking; 2) childhood exposure to environmental tobacco smoke (ETS). Objectives. To explore these two possible risk factors for acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), we analyzed data collected in a large case control study (SETIL) primarily designed to evaluate the role of electromagnetic fields in childhood haematopoietic malignancies. Methods.We focused on incident cases (with informed consent) of ALL (n=602) and AML (n=83) in 14 Italian Regions during 1998- 2001, individually matched (2:1) by age, sex and Region with controls randomly drawn from the general population (matching was broken in the present analysis). We conducted separate logistic regressions for ALL and AML, conditioned to Region and adjusted for child age and sex. Results. Analysis of AML data showed a 3-way interaction (p=0.003) between paternal preconception smoking, maternal smoking during pregnancy, and maternal age. Remarkably, heavy smokers (>10 cigarettes/day) appeared to be at raised risk of having a child affected by childhood AML when maternal age was <30 years (OR 5.4; 95%CI 1.6-18.2; reference category, never-smoker parents); we were unable to find any sign of smoking-related risk above this cut-off (based on median maternal age). No clear association emerged for ETS. Analysis of ALL data showed raised risk for children regularly exposed (>=1 cigarette/day) to ETS (OR 1.5; 95%CI 1.1-2.0; reference, never exposed); intriguingly, risk appeared more pronounced (OR 2.5; 95%CI 1.4-4.4) in “late-onset” cases (age >=6 years). No association was detected with prenatal exposure. Conclusion.We hypothesize that young maternal age could modulate risks of childhood AML determined by parental smoking (plausibly due to age-related metabolic differences). This study also supports the concept that childhood exposure to ETS could be a risk factor for ALL.