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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

doi: 10.1097/CMR.0000000000000106
ORIGINAL ARTICLES: Epidemiology

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 μmol/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.

Departments of aEpidemiology

bSurgical Oncology

cPathology

dDermatology

eMelanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

fCancer Biology

gDuke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA

* In memory of the 10th death anniversary of Dr T.C. Hsu, Professor in the Department of Cancer Biology, who died in 2003.

Present address: Chunying Li: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China.

Correspondence to Li-E Wang, MD, Department of Epidemiology, Unit 1365, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA Tel: +1 713 745 6862; fax: +1 713 563 0999; e-mail: lwang@mdanderson.org

Received August 31, 2013

Accepted May 23, 2014

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