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Published on: February 12, 2015
Gene expression in the oropharynx of children exposed to secondhand smoke
Samuel T Ostrower1, Tova C Fischer, Richard V Smith
1Department of Otorhinolaryngology-Head and Neck Surgery, Division of Head and Neck Surgery, Montefiore Medical Center, New York, USA.
Insights
Secondhand smoke exposure alters gene expression in children's oropharyngeal mucosa. This pilot study reveals significant changes in genes related to cancer and cell growth, potentially impacting future health.
Area of Science:
- Environmental Health
- Molecular Biology
- Pediatrics
Background:
- Secondhand smoke (SHS) exposure is a significant environmental risk factor for pediatric health.
- Oropharyngeal mucosa is a primary site of contact with inhaled environmental toxins.
- Gene expression alterations in response to SHS may indicate early molecular changes associated with disease development.
Purpose of the Study:
- To compare gene expression profiles in the oropharyngeal mucosa of children with and without SHS exposure.
- To identify specific genes and molecular pathways affected by SHS in children.
Main Methods:
- Prospective case-control study involving 41 children (2-6 years old) undergoing tonsillectomy.
- Assessment of SHS exposure using a validated parental questionnaire.
- Genome-wide gene expression analysis using microarrays on oropharyngeal mucosal samples.
Main Results:
- 318 cDNA clones significantly distinguished between SHS-exposed (ex+) and unexposed (ex-) children (P < .01).
- 180 genes were overexpressed and 138 underexpressed in the ex+ group.
- Affected genes were enriched in pathways including cancer, cell cycle, and cell growth/proliferation.
Conclusions:
- SHS exposure induces significant gene expression changes in the oropharyngeal mucosa of children.
- These molecular alterations may have long-term implications for disease development.
- This pilot study provides evidence supporting the link between SHS and early molecular changes in children's respiratory tract.
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.
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