Original Article
Subject Categories: Photobiology
Journal of Investigative Dermatology (2007) 127, 196–205. doi:10.1038/sj.jid.5700481; published online 13 July 2006
4-Nitroquinoline-1-Oxide-Induced Mutagen Sensitivity and Risk of Nonmelanoma Skin Cancer: A Case–Control Analysis
Li-E Wang1, T C Hsu2,
, Ping Xiong1, Sara S Strom1, Madeleine Duvic3, Gary L Clayman4, Randal S Weber4, Scott M Lippman5, Leonard H Goldberg6 and Qingyi Wei1
- 1Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
- 2Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
- 3Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
- 4Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
- 5Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
- 6DermSurgery Associates, Houston, Texas, USA
Correspondence: Dr Qingyi Wei, Department of Epidemiology, Unit 1365, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030, USA. E-mail: qwei@mdanderson.org
This report is in memory of Dr T.C. Hsu, Professor in the Department of Cancer Biology, who died in 2003.
Received 29 December 2005; Revised 21 March 2006; Accepted 12 April 2006; Published online 13 July 2006.
Abstract
The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) is thought to induce squamous cell carcinoma (SCC) similar to those induced by UV radiation in animals. Therefore, we tested the hypothesis that cellular sensitivity to 4-NQO is associated with risk of developing skin cancer in a case–control study of 191 patients with nonmelanoma skin cancer (NMSC; 81 SCC and 110 basal cell carcinoma (BCC)) and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10
M for 24 hours and scored for chromatid breaks in 50 well-spread metaphases. We found that the mean frequency of chromatid breaks per cell (b/c) was significantly higher in the cases (mean
SD, 0.46
0.43 for SCC and 0.43
0.38 for BCC) than in the controls (0.25
0.25; P<0.001 for both comparisons) and were associated with more-than-twofold increased risk for both SCC and BCC after adjustment for known risk factors. Therefore, our findings support the notion that sensitivity to 4-NQO reflects susceptibility to UV-induced NMSC. However, there is a lack of correlation between UVB-induced b/c and 4-NQO-induced b/c in this study population. Therefore, these findings need to be verified by additional studies.
Abbreviations:
BCC, basal cell carcinoma; b/c, breaks per cell; CI, confidence interval; NMSC, nonmelanoma skin cancer; SCC, squamous cell carcinoma; OR, odds ratio; 4-NQO, 4-nitroquinoline-1-oxide
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