TY - JOUR
T1 - Repair capacity for UV light-induced DNA damage associated with risk of nonmelanoma skin cancer and tumor progression
AU - Wang, Li E.
AU - Li, Chunying
AU - Strom, Sara S.
AU - Goldberg, Leonard H.
AU - Brewster, Abenaa
AU - Guo, Zhaozheng
AU - Qiao, Yawei
AU - Clayman, Gary L.
AU - Lee, J. Jack
AU - El-Naggar, Adel K.
AU - Prieto, Victor G.
AU - Duvic, Madeleine
AU - Lippman, Scott M.
AU - Weber, Randal S.
AU - Kripke, Margaret L.
AU - Wei, Qingyi
PY - 2007/11/1
Y1 - 2007/11/1
N2 - 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 (P trend = 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.
AB - 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 (P trend = 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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U2 - 10.1158/1078-0432.CCR-07-0969
DO - 10.1158/1078-0432.CCR-07-0969
M3 - Article
C2 - 17975167
AN - SCOPUS:35948952401
VL - 13
SP - 6532
EP - 6539
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 21
ER -