Gene expression in the oropharynx of children exposed to secondhand smoke

Objectives/Hypothesis: To compare gene expression in oropharyngeal mucosa of children with (ex+) and without (ex-) secondhand smoke exposure. Study Design: Prospective case-control. Methods: Forty-one age- and gender-matched children (2-6 years old) undergoing tonsillectomy for sleep disordered breathing at a tertiary care children's hospital were assessed for secondhand smoke exposure. Parental response to a validated questionnaire relating to secondhand smoke exposure governed inclusion. Sixteen samples were selected for microarray analysis (7 ex+, 9 ex-). Following tonsillectomy, ex vivo brushing of the mucosa isolated total RNA. Genome-wide expression profiles were generated by comparing sample RNA to a reference of all samples, assessing 27,323 cDNA clones. Microarray clones were ranked according to their ability to distinguish between the two groups using a Student t test. Results: A total of 318 cDNA clones distinguished the two groups (P <.01); 180 genes were overexpressed and 138 underexpressed in ex+ samples relative to the ex- group. Independent analysis of these two groups sorted genes into disease processes and molecular functional groups, including cancer (34 genes in the overexpressed group, 29 underexpressed, P <.05), cell cycle (14 and 10), and cell growth and proliferation (7 and 11). Two of the upregulated genes, LCN2 and IQGAP1, have been previously linked to inflammation in smokers and response/repair to cellular injury in bronchial epithelium. Conclusions: Findings in this pilot study support the hypothesis that secondhand smoke exposure seems to induce gene expression changes in the oropharyngeal mucosa of exposed children, which may have significant implications for current and future disease processes.