title: Duration but not intensity of alcohol and tobacco exposure predicts p16INK4A homozygous deletion in head and neck squamous cell carcinoma.
abstract: 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 p16INK4A 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 p16INK4A gene. Hypothesizing that p16INK4A homozygous deletion is associated with tobacco and alcohol exposure, we investigated 330 consecutive HNSCC tumors. The odds ratio (OR) for p16INK4A 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 < or = 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 < or = 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.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Kim S
authors.initials: KS
authors.lastname: Kraunz
authors.forename: Michael D
authors.initials: MD
authors.lastname: McClean
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.forename: Edward
authors.initials: E
authors.lastname: Peters
authors.forename: Henry
authors.initials: H
authors.lastname: Calderon
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16