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

Abstract

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.

• Authors: Yong Zhu, Margaret R Spitz, Yun-Ling Zheng, Waun K Hong, Xifeng Wu
• Journal: Cancer (Cancer) Vol. 95 Issue 3 Pg. 563-8 (Aug 01 2002) ISSN: 0008-543X [Print] United States
• PMID: 12209748 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2002 American Cancer Society.

Chemical References

• Carcinogens
• 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Topics

• 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (adverse effects)
• Aged
• Carcinogens (adverse effects)
• Carcinoma, Squamous Cell (genetics, pathology)
• Chromosome Aberrations (chemically induced)
• Chromosomes, Human, Pair 3 (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Genetic Testing
• Head and Neck Neoplasms (genetics, pathology)
• Humans
• In Situ Hybridization, Fluorescence
• Lymphocytes (drug effects, metabolism)
• Male
• Middle Aged
• Predictive Value of Tests