title: Association between cigarette smoking and FHIT gene alterations in lung cancer.
abstract: 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.
authors.affiliation: Division of Experimental Oncology A, Instituto Nazionale Tumori, Milan, Italy. sozzi@istitutotumori.mi.it
authors.forename: G
authors.initials: G
authors.lastname: Sozzi
authors.forename: L
authors.initials: L
authors.lastname: Sard
authors.forename: L
authors.initials: L
authors.lastname: De Gregorio
authors.forename: A
authors.initials: A
authors.lastname: Marchetti
authors.forename: K
authors.initials: K
authors.lastname: Musso
authors.forename: F
authors.initials: F
authors.lastname: Buttitta
authors.forename: S
authors.initials: S
authors.lastname: Tornielli
authors.forename: S
authors.initials: S
authors.lastname: Pellegrini
authors.forename: M L
authors.initials: ML
authors.lastname: Veronese
authors.forename: G
authors.initials: G
authors.lastname: Manenti
authors.forename: M
authors.initials: M
authors.lastname: Incarbone
authors.forename: A
authors.initials: A
authors.lastname: Chella
authors.forename: C A
authors.initials: CA
authors.lastname: Angeletti
authors.forename: U
authors.initials: U
authors.lastname: Pastorino
authors.forename: K
authors.initials: K
authors.lastname: Huebner
authors.forename: G
authors.initials: G
authors.lastname: Bevilaqua
authors.forename: S
authors.initials: S
authors.lastname: Pilotti
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: M A
authors.initials: MA
authors.lastname: Pierotti
mesh_terms: D017766:Acid Anhydride Hydrolases; D002872:Chromosome Deletion; D002873:Chromosome Fragility; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase