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Duration but not Intensity of Alcohol and Tobacco Exposure Predicts p16^INK4A Homozygous Deletion in Head and Neck Squamous Cell Carcinoma

Departments of ¹ Genetics and Complex Diseases and ² Environmental Health, Harvard School of Public Health; ³ Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts; and ⁴ Louisiana State University Health Sciences Center, School of Public Health, New Orleans, Louisiana

Requests for reprints: Karl T. Kelsey, Department of Genetics and Complex Diseases, Harvard School of Public Health, Room 607, Building I, 665 Huntington Avenue, Boston, MA 02115. Phone: 617-432-3313; Fax: 617-432-0107; E-mail: kelsey{at}hsph.harvard.edu.

In tobacco-associated solid tumors, evidence suggests that the pattern of carcinogen exposure is related to the nature of somatic gene inactivation within crucial pathways, including the retinoblastoma (Rb) pathway. One somatic event in this pathway, homozygous deletion of the p16^INK4A gene, is commonly observed in head and neck squamous cell carcinoma (HNSCC). Alcohol and tobacco are both well-established risk factors for HNSCC but there has been little characterization of the relationship of exposure to these carcinogens and inactivation of the p16^INK4A gene. Hypothesizing that p16^INK4A homozygous deletion is associated with tobacco and alcohol exposure, we investigated 330 consecutive HNSCC tumors. The odds ratio (OR) for p16^INK4A homozygous deletion among alcohol consumers in the upper tertile (>43 years used) was 5.2 [95% confidence interval (95% CI), 2.1-12.8] as compared with those with 43 years of alcohol consumption. Intensity of alcohol exposure, measured as average alcoholic drinks per week, was not associated with gene deletion. When we examined the distribution of duration of tobacco use, the OR for p16^INK4A homozygous deletion was 1.3 (95% CI, 0.5-3.0) and 1.9 (95% CI, 0.9-4.0) for 29 to 39 years and >39 years of tobacco smoking, respectively, as compared with those that smoked 28 years. As in the case of alcohol use, intensity of tobacco exposure (measured as packs per day) was not associated with gene deletion. Hence, the duration of alcohol use and duration of smoking, but not intensity of either, significantly predicted p16^INK4A homozygous deletion in HNSCC. (Cancer Res 2006; 66(8): 4512-5)