Maternal smoking and risk of childhood cancer: a report from the Childhood Cancer and Leukemia International Consortium.
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BACKGROUND: Although tobacco is an established carcinogen and components of tobacco smoke may cross the placental membrane, past studies of maternal prenatal smoking and childhood cancer have resulted in mixed or null results. However, many studies have relied on case-control methods and may be susceptible to various biases. We aimed to elucidate the nature of the relationship between maternal prenatal smoking and childhood cancer through a multinational analysis of prospectively recorded record-linkage studies with probabilistic bias methods. METHODS: Data for this analysis came from existing population-based case-control record-linkage studies in the Childhood Cancer and Leukemia International Consortium, with studies from the USA, Sweden, Finland, and Denmark, including more than 20 000 cases and 300 000 controls. We assessed the association between maternal prenatal smoking and childhood cancer using logistic regression. Additionally, we conducted probabilistic bias analysis to investigate the effect of exposure misclassification using sensitivities and specificities from biomarker-based validation studies. RESULTS: Both before and after bias adjustment, maternal smoking was not found to be associated with most cancers investigated. Maternal prenatal smoking was inversely associated with paediatric melanoma [bias-adjusted odds ratio (OR) 0.68, 95% simulation interval (SI): 0.47-0.98] and skin carcinomas and other/unspecified carcinomas (bias-adjusted OR: 0.72, 95% SI: 0.52-0.96), and positively associated and unspecified malignant tumours (bias-adjusted OR: 1.50, 95% SI: 1.21-1.84). CONCLUSIONS: This analysis supports previous findings that there is little evidence of an effect of maternal prenatal smoking on childhood cancer risk, with few potential exceptions. However, due to numerous other detrimental effects, public health efforts should continue to further reduce its prevalence.