Abstract
BackgroundA recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals.MethodsWe assessed 9 functional polymorphisms in 6 genes that affect the metabolism of polycyclic aromatic hydrocarbons (PAH) to evaluate potential interactions with parental smoking during pregnancy in a population-based case-control study of childhood brain tumors. Cases (N = 202) were ≤10 years old, diagnosed from 1984–1991 and identified in three Surveillance, Epidemiology, and End Results (SEER) registries in the western U.S. Controls in the same regions (N = 286) were frequency matched by age, sex, and study center. DNA for genotyping was obtained from archived newborn dried blood spots.ResultsWe found positive interaction odds ratios (ORs) for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P interaction = 0.02; 0.10), such that children with the high-risk (greater PAH activation) genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. A dose-response pattern for paternal smoking was observed among children with the EPHX1 H139R high-risk genotype only (ORno exposure = 1.0; OR≤3 hours/day = 1.32, 95% CI: 0.52–3.34; OR>3hours/day = 3.18, 95% CI: 0.92–11.0; P trend = 0.07).ConclusionParental smoking during pregnancy may be a risk factor for childhood brain tumors among genetically susceptible children who more rapidly activate PAH in tobacco smoke.
Highlights
The association between parental smoking during pregnancy and risk of childhood brain tumors is inconsistent in the literature
Cases were identified through the Surveillance, Epidemiology and End Results (SEER) registries in the Los Angeles, San FranciscoOakland, and Seattle regions, and include children diagnosed with a tumor of the brain, cranial nerves, or meninges [International Classification of Diseases-Oncology (ICD-O) (World Health Organization 1976) codes 191.0–192.1] between 1984–1991
No exposure to tobacco smoke during pregnancy Mother smoked during pregnancy Mother only Mother and other passive/fatherc 1–10 cigarettes/day 11+ cigarettes/day P for trend
Summary
The association between parental smoking during pregnancy and risk of childhood brain tumors is inconsistent in the literature. Many studies have evaluated parental smoking and childhood brain tumors, none have evaluated potential interactions with functional polymorphisms in genes whose enzyme products metabolize tobacco smoke carcinogens, such as polycyclic aromatic hydrocarbons (PAH). Animal studies suggest this class of chemicals may possibly affect brain tumor risk [23,24]. A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals
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