Increased risk of human lung adenocarcinoma is associated with the rare alleles of the Hras1 minisatellite locus

Data on allelotyping of minisatellite sequence within the Hras1 protooncogene locus in 60 patients with lung adenocarcinoma (LAC) are presented. Allele distribution was analyzed with respect to the effect of tobacco smoke carcinogens (smoking factor). Results; were compared with the analogous data obtained for patients:with squamous-cell-carcinoma and for individuals without cancer. In contrast to the patients with squamous cell-carcinoma, the frequency of the Hras1 locus rare alleles in patients with lung-adenocarcinoma was higher than in individuals without cancer. More striking difference between the latter groups was demonstrated for nonsmoking patients (17.6% versus 2.7% of healthy individuals, P = 0.0005). In smoking LAC patients, higher frequencies of the common a4 allele (2.5 kb in size under the MspI/HpaII digestion) were found. Our findings point to the combined effect of endogenous and exogenous factor's on the development of lung adenocarcinomas in humans. In this work, we discuss the possible mechanism of association between the rare minisatellite alleles and the predisposition to lung cancer.