Elevated Urinary 1‐HOP, NNN, and NNAL in Smokers with Head and Neck Squamous Cell Carcinoma

Abstract

Objective: Tobacco metabolites have been shown to be markers of tobacco exposure as well as markers of lung cancer risk. To this point, tobacco metabolites have not been studied in head and neck squamous cell carcinoma (HNSCC). We seek to study tobacco metabolites in smokers with (subjects) and without (controls) HNSCC. Method: Smokers with head and neck cancer were enrolled after they completed a detailed smoking history questionnaire. Urine samples were collected in standard fashion. Controls consisted of smokers without HNSCC. Urinary levels of total 1-hydroxypyrene (1-HOP) and total 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) and N′-nitrosonornicotine (NNN) were assayed using high performance liquid chromatography (HPLC). Results: In this pilot study, NNN data were available in 27 subjects, NNAL in 19 subjects, and 1-HOP in 18 subjects. Control matching for NNN was done with a 1:1 ratio. Controls were matched on cigarettes per day in a 3:1 ratio for NNAL and 1-HOP to increase power. T test was used to compare study subjects with controls. Mean levels for subjects (S) and controls (C) were: NNN [S:0.12 pmol/ml, C:0.06 pmol/ml ( P = .06)], NNAL [S:1.53 pmol/ml, C:1.25 pmol/ml ( P = .3)], and 1-HOP [S:1.88 pmol/ml, C:0.84 pmol/ml ( P = .001)], respectively. Conclusion: 1) Smokers with HNSCC have higher urinary 1-HOP (significant) and NNN (near significant) compared with matched controls. 2) The data suggest smokers who develop HNSCC process carcinogens differently than smokers without HNSCC. 3) This data is a first step toward understanding why some smokers develop carcinoma while others do not.