A Role for Epigenetics in Broadening the Scope of Pediatric Care in the Prevention of Adolescent Smoking

Abstract

Adolescence presents a critical opportunity to support the development of healthy patterns of behavior and prevent future health problems. Unfortunately, there is not yet a well-developed prevention model that allows pediatricians to initiate and monitor prevention efforts for the substantial minority of individuals who engage in risky behavior during adolescence. We suggest that recently developed epigenetic technologies may provide a bridge to a new prevention paradigm in which pediatricians screen for indicated smoking prevention services. Specifically, since currently available tobacco use screening measures are insensitive to low levels of use, newly developed methylation based approaches may enhance the sensitivity of the initial screening for nascent smoking behavior as well monitoring of outcomes. We conclude that the incorporation of Next Gen screening technologies into standard pediatric evaluations may allow for more effective referral to prevention programming for tobacco use. In addition to the potential direct impact on long-term enhancement of health outcomes secondary to smoking prevention, well-established links between smoking and other risk behaviors suggest that expanded referral for nascent smoking may also create opportunities to address other risky adolescent behaviors, and so decrease several interrelated drivers of long-term health care costs.

Keywords: Aryl hydrocarbon receptor repressor; DNA methylation; cotinine; pediatrics; smoking prevention.

Fig. 1

A new model for smoking prevention programming. In this new paradigm, earlier referral to prevention programming is facilitated by pediatric screening during routine well-child health assessments and immunization visits. After a positive initial screen is received (from either self report or biological assessments of cotinine or methylation status), the pediatrician assesses the patient for the appropriate intervention. After the intervention, the patient is periodically monitored to facilitate the early recognition of relapse and re-referral into more intensive services.

Fig. 2

Exposure of cells to dioxins or polyaromatic hydrocarbons (PAH) found in tobacco smoke results in the induction of the AHR nuclear receptor/xenobiotic metabolism pathway. Once AHR binds either dioxin or PAH, it binds to its heterodimer partner, the AHR Nuclear Translocator (ANRT). Together, they move to the nucleus and induce P450 genes such as CYP1A1 that are critical to the catabolism of tobacco related substances. Unchecked, this catabolic activity is detrimental. However, this activity also induces the demethylation of cg05575921. This demethylation allows the enhancer motif surrounding cg05575921 to bind factors that increase AHRR transcription. The resulting AHRR receptor provides feedback modulation of AHR induced transcription by competing with AHR for ARNT and by competing with AHR for xenobiotic receptor enhancer (XRE) motifs.