title: 4-nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis.
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 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 (P(trend)=0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (P(interaction)=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.
authors: 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.
authors: Li-E
authors: LE
authors: Wang
authors: Chunying
authors: C
authors: Li
authors: Ping
authors: P
authors: Xiong
authors: Jeffrey E
authors: JE
authors: Gershenwald
authors: Victor G
authors: VG
authors: Prieto
authors: Madeleine
authors: M
authors: Duvic
authors: Jeffrey E
authors: JE
authors: Lee
authors: Elizabeth A
authors: EA
authors: Grimm
authors: Tao C
authors: TC
authors: Hsu
authors: Qingyi
authors: Q
authors: Wei
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000328:Adult; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D012307:Risk Factors; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide