Background. Carcinogens leave their """"""""signatures"""""""" in tumors in the form of characteristic genetic damage. One of the best examples is a molecular """"""""signature"""""""" of tobacco smoke in the p53 tumor suppressor gene from lung cancers. Although highly specific, this imprimatur occurs in less than 20% of tumors, so a more common marker is needed. A recent report showed that allelic deletion occurs more often in lung cancers from smokers than nonsmokers, that the distribution of damage differs in these groups, and that statistically meaningful differences could be discerned in studies of modest size. If confirmed and extended, this approach might define a useful genetic marker for tobacco carcinogens as well as a new tool for investigating cancer etiology.Principal Hypothesis. Carcinogens in tobacco smoke cause recognizable patterns of allelic deletion at characteristic chromosomal locations.
Specific Aims. [I] Determine patterns and frequencies of allelic deletion in early stage, lung adenocarcinomas from forty white women including 20 smokers and 20 never-smokers. [II] Analyze data from Aim I to assess the feasibility and cost of developing a sensitive and specific signature of genetic damage caused by tobacco smoke. [III] Compare the character of allelic deletion at chromosome 9p in early stage lung adenocarcinomas from smokers and nonsmokers.Samples & Laboratory Methods. Twenty, early stage lung adenocarcinomas from smoking women will be matched by age, stage, histology, gender and ethnicity to 20 lung cancers from never-smokers. Allelic deletion will be tested at 16 chromosomal loci commonly lost in lung cancers from smokers and never-smokers.Data Analysis. Multivariate analysis will test coordinate genetic losses for power to discriminate prior exposure to tobacco smoke.
