Direct correlation between FRA3B expression and cigarette smoking.
Cytogenetic deletions and/or loss of heterozygosity (LOH) of the short arm of chromosome 3, often with a break at 3p14, are well documented in lung tumors. The coincidence of a chromosomal fragile site, FRA3B, at a common chromosomal breakpoint in lung cancer has suggested that fragility at this site may predispose to breakage that could contribute to multistep carcinogenesis. This idea is supported by the more recent finding that FRA3B maps within the FHIT (fragile histadine triad) gene, and that aberrant transcripts and genomic deletions of FHIT/FRA3B occur in a variety of tumors including lung tumors. To determine whether some individuals have increased fragility of FRA3B that might increase the risk for breakage or deletion in 3p14.2, fragile site expression was examined in smokers, nonsmokers, and small cell lung cancer (SCLC) patients. The data clearly show that active smokers exhibit a significantly higher frequency of fragile site expression, including FRA3B, compared to that of nonsmokers and patients diagnosed with SCLC who have stopped smoking. These results suggest that active tobacco exposure increases chromosome fragile site expression, and that this fragility is transient and reversible. The data support the hypothesis that exposure to tobacco carcinogens increases the potential for chromosome breakage at fragile sites.
Stein
Constance K
CK
Departments of Pathology and Pediatrics, State University of New York Upstate Medical University, Syracuse, NY 13210, USA. steinc@upstate.edu
Glover
Thomas W
TW
Palmer
J Lynn
JL
Glisson
Bonnie S
BS
D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000209:etiology / Q000235:genetics; D002872:Chromosome Deletion; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D012907:Smoking / Q000235:genetics*