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


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).


CONCLUSIONS
Multiple deletions occurred more frequently in nonsmokers and predicted a higher risk of early recurrence.
Department of Surgery, Memorial Hospital, New York, New York.
W M
WM
Lydiatt
B J
BJ
Davidson
J
J
Shah
S P
SP
Schantz
R S
RS
Chaganti
D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D012907:Smoking / Q000235:genetics*