CYCLIN D1 ABNORMALITIES AND TOBACCO EXPOSURE IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Background. Amplification of the cyclin D1 (CCND1) gene, which encodes a cell cycle regulating protein, has been described in several solid tumors including head and neck squamous cell carcinoma (HNSCC). While correlations between CCND1 amplification and tumor behavior have been suggested, no investigation has focused on risk factor exposure as a p otential cause of CCNC1 alteration. Methods: Southern blotting was use d to identify CCND1 amplification in 57 previously untreated HNSCC tum or specimens. Tissue from 27 cases was analyzed for CCND1 mRNA express ion by Northern blot analysis. Results: In 13/57 (23%) cases, a 2-5 fo ld amplification of CCND1 was found. CCND1 mRNA expression was higher in amplified than in non-amplified tumors and supported an association between CCND1 amplification and increased expression of CCND1 mRNA. N o correlation was found between CCND1 amplification or CCND1 expressio n and clinical or pathological parameters. However, analysis of risk f actor exposure revealed that patients with greater tobacco exposure we re more likely to have tumors with CCND1 amplification (p = .037), Als o, tobacco exposure was correlated with CCND1 expression in tumors. Co nclusion: Tobacco exposure is a well-known risk factor for HNSCC. CCND 1 amplification and alterations in expression may be causally related to tobacco carcinogen exposure and lead to a loss Of cell cycle regula tion.