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
eMelanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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: firstname.lastname@example.org
Received August 31, 2013
Accepted May 23, 2014