The relationship of loss of heterozygosity to tobacco exposure and early recurrence in head and neck squamous cell carcinoma.

ABSTRACT

BACKGROUND: Tobacco usage contributes to carcinomas of the lung, bladder, esophagus, uterine cervix, and head and neck, and can induce specific genetic lesions. Studies of the above tumor types have documented allelic deletions affecting 3p, 5q, 9p, 9q, 10q, 11p, 13q, 17p, and 18q. Relationships between genetic loss, tobacco exposure, and patient outcome have not been described. PATIENTS AND METHODS: To confirm and further define loss of heterozygosity in head and neck squamous cell carcinoma (HNSCC), and to examine relationships between loss of heterozygosity and both tobacco exposure and early recurrence, we undertook this study on previously untreated patients with HNSCC. We performed a Southern blot analysis using 11 probes specific for loci deleted in tobacco-associated cancers. We have investigated 42 prospectively collected, paired samples of HNSCC and peripheral blood. Demographic and follow-up data were collected on these patients. RESULTS: Significant loss of heterozygosity was observed in descending order of frequency at 11p, 9p, 17p, 3p, 10q, and 13q. All nonsmokers showed loss of heterozygosity on one or more loci compared with only 53% of smokers (P < 0.05). Furthermore, patients with multiple deletions had a significantly higher rate of early recurrence than those with fewer deletions (P < 0.05). CONCLUSION: Multiple deletions occurred more frequently in nonsmokers and predicted a higher risk of early recurrence.