Molecular and cellular alterations in tobacco smoke-associated larynx cancer

Tumours of head and neck belong to the most frequent types of cancer world- wide. In Poland, mortality from larynx cancer among males has been continuo usly increasing during the last decades up to 8.4 deaths per 100,000 men in 1993, which exceeds epidemiological records from other countries. The aeti ology of laryngeal cancer is strongly associated with exposure to carcinoge ns present in tobacco smoke. The review describes a sequence of molecular a nd cellular events from carcinogenic exposure, DNA adduct formation, detect ion of mutations in the p53 gene, loss of heterozygosity (LOH) in chromosom al loci encoding the p53 and p16 genes, and loss of control of the cell cyc le. The section concerning DNA adducts includes a discussion of the role of such confounders as exogenous exposure, the age and sex of the subject, an d disease progression. The significance of genetic factors as individual ri sk determinants is discussed in relation to bleomycin-induced chromosome in stability and in connection with the occurrence of defects in genes encodin g detoxifying enzymes, The question concerning the substantial difference b etween men and women in larynx cancer morbidity and mortality remains open, even when the significantly higher adduct formation in male DNA compared w ith female material was taken into account. Preliminary experiments suggest a role of the frequently observed loss of the Y-chromosome. (C) 1999 Elsev ier Science B.V. All rights reserved.