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BPDE-induced lymphocytic 3p21.3 aberrations may predict head and neck carcinoma risk
Yong Zhu1, Margaret R Spitz, Yun-Ling Zheng
1Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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.