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Int. J. Mol. Sci. 2018, 19(1), 242; doi:10.3390/ijms19010242

A Case-Control Study of the Genetic Variability in Reactive Oxygen Species—Metabolizing Enzymes in Melanoma Risk

1
Program in Public Health, University of California Irvine, Irvine, CA 92697, USA
2
Department of Neurobiology and Behavior, School of Biological Sciences, University of California Irvine, Irvine, CA 92697, USA
3
Department of Biomedical Engineering, The Henry Samueli School of Engineering, University of California Irvine, Irvine, CA 92697, USA
4
Department of Epidemiology, School of Medicine, University of California, Irvine, CA 92697, USA
5
Chao Family Comprehensive Cancer Center, Irvine, CA 92697, USA
*
Author to whom correspondence should be addressed.
Received: 18 December 2017 / Revised: 9 January 2018 / Accepted: 12 January 2018 / Published: 14 January 2018
(This article belongs to the Special Issue Chemically-Induced DNA Damage, Mutagenesis, and Cancer)
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Abstract

Recent studies have shown that ultraviolet (UV)-induced chemiexcitation of melanin fragments leads to DNA damage; and chemiexcitation of melanin fragments requires reactive oxygen species (ROS), as ROS excite an electron in the melanin fragments. In addition, ROS also cause DNA damages on their own. We hypothesized that ROS producing and metabolizing enzymes were major contributors in UV-driven melanomas. In this case-control study of 349 participants, we genotyped 23 prioritized single nucleotide polymorphisms (SNPs) in nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4 (NOX1 and NOX4, respectively), CYBA, RAC1, superoxide dismutases (SOD1, SOD2, and SOD3) and catalase (CAT), and analyzed their associated melanoma risk. Five SNPs, namely rs1049255 (CYBA), rs4673 (CYBA), rs10951982 (RAC1), rs8031 (SOD2), and rs2536512 (SOD3), exhibited significant genotypic frequency differences between melanoma cases and healthy controls. In simple logistic regression, RAC1 rs10951982 (odds ratio (OR) 8.98, 95% confidence interval (CI): 5.08 to 16.44; p < 0.001) reached universal significance (p = 0.002) and the minor alleles were associated with increased risk of melanoma. In contrast, minor alleles in SOD2 rs8031 (OR 0.16, 95% CI: 0.06 to 0.39; p < 0.001) and SOD3 rs2536512 (OR 0.08, 95% CI: 0.01 to 0.31; p = 0.001) were associated with reduced risk of melanoma. In multivariate logistic regression, RAC1 rs10951982 (OR 6.15, 95% CI: 2.98 to 13.41; p < 0.001) remained significantly associated with increased risk of melanoma. Our results highlighted the importance of RAC1, SOD2, and SOD3 variants in the risk of melanoma. View Full-Text
Keywords: melanoma; reactive oxygen species; ROS; NADPH oxidase; single nucleotide polymorphisms; SNP; superoxide dismutase; SOD2; SOD3; RAC1 melanoma; reactive oxygen species; ROS; NADPH oxidase; single nucleotide polymorphisms; SNP; superoxide dismutase; SOD2; SOD3; RAC1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yuan, T.-A.; Yourk, V.; Farhat, A.; Ziogas, A.; Meyskens, F.L.; Anton-Culver, H.; Liu-Smith, F. A Case-Control Study of the Genetic Variability in Reactive Oxygen Species—Metabolizing Enzymes in Melanoma Risk. Int. J. Mol. Sci. 2018, 19, 242.

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