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Clinical Cancer Research 13, 6532-6539, November 1, 2007. doi: 10.1158/1078-0432.CCR-07-0969
© 2007 American Association for Cancer Research

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Cancer Susceptibility and Prevention

Repair Capacity for UV Light–Induced DNA Damage Associated with Risk of Nonmelanoma Skin Cancer and Tumor Progression

Li-E Wang1, Chunying Li1, Sara S. Strom1, Leonard H. Goldberg9, Abenaa Brewster2, Zhaozheng Guo1, Yawei Qiao1, Gary L. Clayman3, J. Jack Lee4, Adel K. El-Naggar5, Victor G. Prieto5, Madeleine Duvic6, Scott M. Lippman7, Randal S. Weber3, Margaret L. Kripke8 and Qingyi Wei1

Authors' Affiliations: Departments of 1 Epidemiology, 2 Clinical Cancer Prevention, 3 Head and Neck Surgery, 4 Biostatistics, 5 Pathology, 6 Dermatology, 7 Thoracic/Head and Neck Medical Oncology, and 8 Immunology, The University of Texas M. D. Anderson Cancer Center; and 9 DermSurgery Associates, Houston, Texas

Requests for reprints: Qingyi Wei, Department of Epidemiology, Unit 1365, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3020; Fax: 713-792-0807; E-mail: qwei{at}mdanderson.org.

Purpose: To examine the role of suboptimal DNA repair capacity (DRC) for UV light–induced DNA damage in the development of nonmelanoma skin cancer (NMSC) and tumor progression.

Experimental Design: We conducted a hospital-based case-control study of 255 patients with newly diagnosed NMSC [146 with basal cell carcinoma (BCC) and 109 with squamous cell carcinoma (SCC)] and 333 cancer-free controls. We collected information on demographic variables and risk factors from questionnaires, tumor characteristics from medical records, and lymphocytic DRC phenotype by the host-cell reactivation assay. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI).

Results: Overall, there was a relative 16% reduction in DRC in NMSC patients compared with controls (P < 0.001 for BCC and for SCC, respectively). DRC below the controls' median value was associated with increased risk significantly for BCC (OR, 1.62; 95% CI, 1.07-2.45) but borderline for SCC (OR, 1.63; 95% CI, 0.95-2.79) after adjustment for age, sex, and other assay-related covariates. When the highest tertile of controls' DRC was used as the reference, the intermediate and low DRC were associated with a statistically significant trend for increasing risk for both BCC (Ptrend = 0.007) and SCC (Ptrend = 0.020). However, patients with aggressive or multiple SCC tended to have a higher DRC than those with nonaggressive or single SCC.

Conclusions: Reduced DRC is an independent risk factor for BCC and single or nonaggressive SCC but not for multiple primaries, local aggressiveness, or recurrence of NMSC.




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Copyright © 2007 by the American Association for Cancer Research.