BPDE-induced lymphocytic 3p21.3 aberrations may predict head and neck carcinoma risk.
Abstact
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.
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.
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.
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.