In vitro benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations in primary lymphocytes, smoking, and risk of squamous cell carcinoma of the head and neck.

Abstract

Cigarette smoking is a major risk factor for squamous cell carcinoma of the head and neck (SCCHN), but only a fraction of those exposed to cigarette smoke develops SCCHN, suggesting variation in individual susceptibility. Tobacco smoke contains a number of carcinogens that cause various kinds of damage to DNA. In this study, we simultaneously measured benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations by the comet assay and the mutagen sensitivity assay, respectively, in cultured primary lymphocytes from newly recruited 123 patients with SCCHN and 136 age- and sex-matched controls. Using the control median as the cut-off, the elevated risk of SCCHN was 2.35 (95% CI, 1.37-4.03), 2.28 (95% CI, 1.34-3.98) and 3.25 (95% CI, 1.85-5.07) for high levels of tail extension, tail length and oliver tail moment of the comet assay, respectively, and 1.75 (95% CI, 1.04-2.94) for high levels of chromosomal aberrations of the mutagen sensitivity assay. The effects of these 2 types of measurements were additive; subjects with high levels of both DNA damage and chromosomal aberrations had a 4.77-fold increased risk (95% CI, 2.73-8.36) of SCCHN. Cigarette smoking further elevated this risk to more than 20-fold (OR 23.6; 95% CI, 8.92-62.3). These data support our previous finding that suboptimal repair contributed to susceptibility to SCCHN and the new data further suggests a possible gene-environment interaction that may play an important role in the etiology of SCCHN. Further validation studies are warranted.

• Authors: Ping Xiong, Zhibin Hu, Chunying Li, Li-E Wang, Adel K El-Naggar, Erich M Sturgis, Qingyi Wei
• Journal: International journal of cancer (Int J Cancer) Vol. 121 Issue 12 Pg. 2735-40 (Dec 15 2007) ISSN: 1097-0215 [Electronic] United States
• PMID: 17724733 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

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

Topics

• 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (toxicity)
• Adult
• Aged
• Carcinogens (toxicity)
• Carcinoma, Squamous Cell (epidemiology, etiology, genetics)
• Case-Control Studies
• Chromosome Aberrations (chemically induced)
• Comet Assay
• DNA Damage (drug effects)
• DNA Repair
• Female
• Genetic Predisposition to Disease
• Head and Neck Neoplasms (epidemiology, etiology, genetics)
• Humans
• Lymphocytes
• Male
• Middle Aged
• Mutagens (toxicity)
• Odds Ratio
• Risk Assessment
• Risk Factors
• Smoking (adverse effects)
• Texas (epidemiology)