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

Int J Cancer. 2007 Dec 15;121(12):2735-40. doi: 10.1002/ijc.23054.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
  • Adult
  • Aged
  • Carcinogens / toxicity*
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / 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
  • Head and Neck Neoplasms / etiology*
  • Head and Neck Neoplasms / genetics
  • Humans
  • Lymphocytes*
  • Male
  • Middle Aged
  • Mutagens / toxicity*
  • Odds Ratio
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects*
  • Texas / epidemiology

Substances

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