Levels of prostaglandin E metabolite, the major urinary metabolite of prostaglandin E₂, are increased in smokers

Purpose: Increased levels of cyclooxygenase-2 and prostaglandin E ₂ (PGE₂) have been observed in tobacco-related malignancies of the upper aerodigestive tract. Moreover, exposure to tobacco smoke can stimulate the synthesis of PGE₂. Recent evidence suggests that urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE ₂ production. In this study, we investigated whether levels of urinary PGE-M were increased in smokers and in patients with head and neck squamous cell carcinoma (HNSCC). Experimental Design: Fifty-eight HNSCC cases and 29 age- and gender-matched healthy controls were prospectively enrolled in the study. A detailed smoking history and single void urine specimen were obtained from each participant. Levels of urinary PGE-M were quantified in a blinded fashion using mass spectrometry and compared with smoking history and tumor status. Results: Adjusted for case-control matching, median urinary PGE-M levels were significantly higher in ever smokers (15.7 ng/mg creatinine) compared with never smokers (9.9 ng/mg creatinine) for the entire study population (n = 87, P = 0.005). Concentrations of urinary PGE-M were nearly doubled in ever smokers (15.2 ng/mg creatinine) versus never smokers (7.8 ng/mg creatinine) among healthy controls (P = 0.001). Higher PGE-M levels were observed in current versus former smokers and in those with greater pack-year exposure. A significant difference in amounts of PGE-M was not observed in patients with HNSCC versus healthy controls. Conclusions: Increased levels of urinary PGE-M were observed in smokers. Urinary PGE-M may have use as a noninvasive biomarker of the effects of tobacco smoke exposure.