Reduced DNA Repair Capacity for Removing Tobacco Carcinogen–Induced DNA Adducts Contributes to Risk of Head and Neck Cancer but not Tumor Characteristics

Abstract

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 ethnicitymatched 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 ∼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. Clin Cancer Res; 16(2); 764-74. ©2010 AACR.

DNA Repair Capacity in Peripheral Lymphocytes Predicts Survival of Patients With Non–Small-Cell Lung Cancer Treated With First-Line Platinum-Based Chemotherapy

“…Both here and in our previous studies in patients with cancers of the lung, skin, or head and neck and in cancer-free controls, 15,19,21,22 we found that DRC in peripheral lymphocytes was lower in females than in males. It is tempting to speculate that the sex influence on prognosis may be mediated in part by DRC levels.…”

“…Although the assay performs reliably in our laboratory, its further application in accredited clinical laboratories needs to be developed. Our previous case-control studies 15,19,21,22 showed that both cell growth after stimulation and baseline reporter (CAT) gene expression of undamaged plasmids after transfection were similar in cases and controls, implying that cells from cases and controls had similar transfection efficiency. Furthermore, even repair-deficient cells, such as xeroderma pigmentosum cells, do not have a reduced transfection efficiency.…”

Genetic polymorphisms in key DNA repair genes and risk of head and neck cancer in a Chinese population

“…Among these, genes involved in the DNA repair pathway are the most investigated due to their vital role in protecting the genome from insults of environmental carcinogens (4,5). Studies have shown inter-individual variations of DNA repair capacity (DRC) in the general population and the effect of a suboptimal DRC on the risk of smoking-related cancers, such as lung cancer and SCCHN (6)(7)(8).…”

DNA Repair Capacity and the Risk of Head and Neck Cancer

“…A level of spontaneous DNA damage tended to increase with tumor grading. The latter result was not confirmed by the analogical study (L. E. Wang et al 2010) done on much bigger group (744 head and neck subjects v. 753 matched cancer-free controls). The conclusion of Wang et al was that the reduced removal of tobacco smoke-induced DNA adducts contributes to the risk of head and neck cancer but does not influence tumor characteristics.…”

“…The most direct way to understand a link between DNA repair deficit and head and neck cancer are studies on processing of tobacco smoke lesions and their removal (Hecht, 2003;L. E. Wang et al, 2010;Wei et al, 1996).…”