Transcriptomics,Genomics

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The effect of intermittent versus continuous low dose aspirin on nasal epithelium gene expression in current smokers: a randomized, double-blinded clinical study


ABSTRACT: A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blind, placebo controlled study in current heavy smokers to compare modulating effects of intermittent versus continuous low dose ASA on gene signatures of smoking and lung cancer from nasal brushings. Fifty-four participants were randomized to intermittent ASA (ASA 81 mg daily for one week alternating with placebo daily for one week) or continuous ASA (81 mg daily) for 12 weeks. The primary endpoint was modulation of a smoking gene signature in nasal brushings. Other [JB1] endpoints included modulation of nasal and bronchial gene signatures for smoking, lung cancer and chronic obstructive pulmonary disease (COPD) and changes in cyclooxygenase (COX)- and 5-lipoxygenase (LOX)-mediated arachidonic acid (ARA) metabolism. Low dose ASA intervention caused minimal changes in smoking and lung cancer gene signature scores in nasal epithelium of current heavy smokers. The small sample size of the intervention groups may have limited the ability to detect modulation of the gene signatures. Low dose ASA lowered urinary prostaglandin E metabolite, a marker of COX-mediated ARA metabolic pathway with no change in urinary leukotriene E4, a marker of 5-LOX-mediated pathway. Exploratory genomic analysis showed that ASA intervention induced wide-ranging genomic changes in the nasal epithelium, including modulation of the arachidonic acid pathway and wound healing. A companion study is underway using ASA plus zileuton to test dual suppression of COX- and 5-LOX-mediated pathways on these gene signature scores in current heavy smokers. Overall design: The study was a single center randomized, double-blinded trial to determine the modulatory effects of intermittent ASA dosing (ASA 81 mg daily for one week alternating with placebo daily for one week) versus continuous ASA dosing (ASA 81 mg daily) for 12 weeks on nasal epithelium gene expression and arachidonic acid metabolism in current smokers. Nasal brushings were collected at baseline, at end of intervention and 7-10 days post intervention.

INSTRUMENT(S): [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [CDF: hugene10st_Hs_ENTREZG_20]

ORGANISM(S): Homo sapiens  

SUBMITTER: Adam C Gower  

PROVIDER: GSE124637 | GEO | 2019-12-24

REPOSITORIES: GEO

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Publications

Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial.

Garland Linda L LL   Guillen-Rodriguez José J   Hsu Chiu-Hsieh CH   Yozwiak Michael M   Zhang Hao Helen HH   Alberts David S DS   Davis Lisa E LE   Szabo Eva E   Merenstein Carter C   Lel Julian J   Zhang Xiaohui X   Liu Hanqiao H   Liu Gang G   Spira Avrum E AE   Beane Jennifer E JE   Wojtowicz Malgorzata M   Chow H-H Sherry HS  

Cancer prevention research (Philadelphia, Pa.) 20190826 11


A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-  ...[more]