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Divisions of Experimental Oncology A [G. S., L. S., L. D. G., K. M., S. T., G. M., M. A. P.] Anatomical Pathology [S. Pi.], and Chest Surgery [M. I.] Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, and Departments of Oncology [A. M., F. B., S. Pe.] and Surgery [A. C., C. A. A., G. B.], Università di Pisa, Pisa, Italy; Royal Brompton Hospital, London, United Kingdom [U. P.]; and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [M. L. V., K. H., C. M. C.]
Epidemiologic data have strongly indicated that cigarette smoking is linked to the development of lung cancer. However, little is known of the molecular targets of carcinogens contained in tobacco smoke. To identify 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, D10S197, 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 only 9 of 40 tumors in nonsmokers (22%). The comparison between the frequency of losses in FHIT in smokers and nonsmokers was statistically significant (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 smoke.
1 This work was supported by grants from the Italian Association for Cancer Research and Special Project Applicazioni Cliniche della Ricerca Oncologica of the Italian National Research Council. L. S. is an Italian Association for Cancer Research Fellow.
2 To whom requests for reprints should be addressed. Phone: 39-2-2390232; Fax: 39-2-2390764; E-mail: sozzi@istitutotumori.mi.it.
Received 3/26/97. Accepted 4/20/97.
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