Reduced DNA repair capacity for removing tobacco carcinogen-induced DNA adducts contributes to risk of head and neck cancer but not tumor characteristics.

Published

Journal Article

PURPOSE: Although cigarette smoking and alcohol use are known risk factors for squamous cell carcinoma of head and neck (SCCHN), only a few exposed individuals develop this disease, suggesting an individual susceptibility. In this study, we investigated the associations between genetically determined DNA repair capacity (DRC) for removing tobacco-induced DNA adducts and risk of SCCHN and tumor characteristics. EXPERIMENTAL DESIGN: We measured DRC in cultured T lymphocytes using the host-cell reactivation assay in a hospital-based case-control study of 744 SCCHN patients and 753 age-, sex-, and ethnicity-matched cancer-free controls recruited from The University of Texas M.D. Anderson Cancer Center. RESULTS: Patients with SCCHN had significantly lower mean DRC (8.84% +/- 2.68%) than controls (9.97% +/- 2.61%; P < 0.0001), and the difference accounted for approximately 2-fold increased risk of SCCHN [adjusted odds ratio (OR), 1.91; 95% confidence interval (CI), 1.52-2.40] after adjustment for other covariates. Compared with the highest DRC quartile of controls, this increased risk was dose dependent (second highest quartile: OR, 1.40; 95% CI, 0.99-1.98; third quartile: OR, 1.87; 95% CI, 1.34-2.62; and fourth quartile: OR, 2.76; 95% CI, 1.98-3.84, respectively; P(trend) < 0.0001). We also assessed the performance of DRC in risk prediction models by calculating the area of under the receiver operating characteristic curve. The addition of DRC to the model significantly improved the sensitivity of the expanded model. However, we did not find the association between DRC and tumor sites and stages. CONCLUSION: DRC is an independent susceptibility biomarker for SCCHN risk but not a tumor marker.

Full Text

Duke Authors

Cited Authors

  • Wang, L-E; Hu, Z; Sturgis, EM; Spitz, MR; Strom, SS; Amos, CI; Guo, Z; Qiao, Y; Gillenwater, AM; Myers, JN; Clayman, GL; Weber, RS; El-Naggar, AK; Mao, L; Lippman, SM; Hong, WK; Wei, Q

Published Date

  • January 15, 2010

Published In

Volume / Issue

  • 16 / 2

Start / End Page

  • 764 - 774

PubMed ID

  • 20068090

Pubmed Central ID

  • 20068090

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-09-2156

Language

  • eng

Conference Location

  • United States