Background:
Tobacco exposure is an established risk factor for head and neck squamous cell carcinoma (hnscc). benzo[alpha]pyrene diol expoxide (bpde), a main metabolic product of the tobacco smoke constituent benzo[alpha]pyrene, induces chromosomal aberrations at specific loci. chromosomal aberrations in peripheral blood lymphocytes (pbls) induced by bpde may reflect individuals' genetic susceptibility to tobacco carcinogens.
Methods:
This study was designed to detect bpde-induced aberrations in pbls at locus 3p21.3 in cultured lymphocytic cells. our hypothesis is that the presence of bpde-induced 3p21.3 aberrations is a biomarker of an individual's genetic susceptibility and that individuals with these aberrations are at an increased risk for hnscc. pbl cultures from 52 cases and 54 controls were treated with 2 microm bpde for 24 hours before the 3p21.3 aberrations were assessed by fluorescence in situ hybridization. one thousand lymphocyte interphases were scored for each sample.
Results:
We found that bpde-induced chromosome 3p21.3 aberrations occurred more frequently in cases (mean: 31.4 per 1000 cells) than in controls (mean: 22.1 per 1000 cells; p < 0.001). however, when 6q27 was selected as a control locus, no such difference was observed (p = 0.545). when the 75th percentile value of induced aberrations in the controls was used as a cutoff point to classify 3p21.3 bpde-induced sensitivity, 30 of the 52 cases (57.69%) and only 14 of the 54 controls (25.93%) were sensitive to bpde exposure. this approach resulted in an odds ratio of 4.8 (95% confidence interval: 1.87-12.28) for hnscc risk associated with bpde-induced 3p21.3 aberrations. there was also a dose-response relationship between the number of bpde-induced aberrations at 3p21.3 and risk for hnscc.
Conclusions:
The results from this study demonstrated that 3p21.3 may be a specific molecular target of tobacco carcinogens and that bpde sensitivity at this locus may reflect an individual's genetic susceptibility to hnscc.