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,malt, Ping Xiong1, Sara S Strom1, Madeleine Duvic3, Gary L Clayman4, Randal S Weber4, Scott M Lippman5, Leonard H Goldberg6 and Qingyi Wei1

  1. 1Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  2. 2Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  3. 3Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  4. 4Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  5. 5Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  6. 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

maltThis 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.

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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 muM 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 (meanplusminusSD, 0.46plusminus0.43 for SCC and 0.43plusminus0.38 for BCC) than in the controls (0.25plusminus0.25; 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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