Skip Navigation LinksHome > Published Ahead-of-Print > 4-Nitroquinoline-1-oxide-induced mutagen sensitivity and ris...
Text sizing:
A
A
A
Melanoma Research:
doi: 10.1097/CMR.0000000000000106
Original article: PDF Only

4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis.

Wang, Li-E; Li, Chunying; Xiong, Ping; Gershenwald, Jeffrey E.; Prieto, Victor G.; Duvic, Madeleine; Lee, Jeffrey E.; Grimm, Elizabeth A.; Hsu, Tao C.; Wei, Qingyi

Published Ahead-of-Print
Collapse Box

Abstract

Mutagen sensitivity assay, which measures the enhanced cellular response to DNA damage induced in vitro by mutagens/carcinogens, has been used in the study of cancer susceptibility. 4-Nitroquinoline-1-oxide (4-NQO), an ultraviolet (UV) radiation-mimetic chemical, can produce chromosomal breaks in mammalian cells and induce cancer. Given the potential role of 4-NQO as the experimental mutagen substituting for UV as the etiological carcinogen of cutaneous melanoma (CM), we tested the hypothesis that cellular sensitivity to 4-NQO is associated with the risk of developing CM in a case-control study of 133 patients with primary CM and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 [mu]mol/l for 24 h and scored chromatid breaks in 50 well-spread metaphases. Multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals. We found that the log-transformed frequency of chromatid breaks was significantly higher in 133 patients than in 176 controls (P=0.004) and was associated with an increased risk for CM (adjusted odds ratio=1.78, 95% confidence interval: 1.12-2.84) after adjustment for age and sex. Moreover, as the chromatid break values increased, the risk for CM increased in a dose-dependent manner (Ptrend=0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (Pinteraction=0.004) on the risk of CM. Therefore, our findings suggest that sensitivity to 4-NQO may be a risk factor for the risk of CM, which is more sensitive than UV-induced chromotid breaks.

Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.