Active and Passive Tobacco Smoke Exposure Cause DNA Damage and Increased Cancer Risk Beginning in the Womb

Objective. This study was conducted to demonstrate the induction of DNA damage and mutation caused by smoking and exposure to environmental tobacco smoke. Background. Human cancer is a multi-step process driven by somatic mutations and epigenetic events that mimic their effects. The frequencies of such events can be increased by occupational, environmental and medical exposures, although relatively few such agents have been unambiguously identified. Tobacco smoke is a pervasive anthropogenic agent proven to be associated with some types of cancer (lung, head and neck) and suspected to be involved in many others. Methods. We applied two well-established assays for locus-specific human somatic mutation, at the hemizygous X-linked gene for the purine scavenger enzyme hypoxanthineguanine phosphoribosyltransferase (HPRT) and the autosomal (heterozygous) determinant for the MN blood group, glycophorin A (GPA) to populations with known smoking status. Results. Smoking was associated with increased somatic mutation in two large studies of healthy individuals. Active smoking, as well of passive exposure, was associated with higher mutation frequencies in a population of young mothers, and in their newborn babies. Molecular analysis revealed that both active and passive exposure to tobacco smoke induced point mutations in the DNA of the children in utero, as well as the products of illegitimate V(D)J recombination, which are responsible for many of the molecular events underlying childhood leukemia. Conclusion. Tobacco smoke represents a widespread if not ubiquitous exposure that contributes to carcinogenesis throughout the body, beginning in the womb. Functional population monitoring therefore represents a feasible and actionable tactic for public health practitioners. Grants. This study was partially funded by grants from the NICHD and the University of Pittsburgh.