ASSOCIATION BETWEEN CIGARETTE-SMOKING AND FHIT GENE ALTERATIONS IN LUNG-CANCER

Epidemiologic data have strongly indicated that cigarette smoking is l inked to the development of lung cancer, However, little is known of t he molecular targets of carcinogens contained in tobacco smoke, To ide ntify genetic lesions characteristic of tobacco damage, we undertook a molecular analysis of microsatellite alterations within the FHIT gene and FRA3B, as well as at an independent locus on chromosome 10, D10S1 97, in lung tumors from heavy smokers and in tumors from never smokers , Loss of heterozygosity affecting at least one Locus of the FHIT gene was observed in 41 of 51 tumors in the smokers group (80%) but in onl y 9 of 40 tumors in nonsmokers (22%), The comparison between the frequ ency of losses in FHIT in smokers and nonsmokers was statistically sig nificant (P = 0.0001), whereas no difference in loss of heterozygosity rate was observed at D10S197 locus. These findings suggest that FHIT is a candidate molecular target of carcinogens contained in tobacco sm oke.