Program in Public Health, University of California Irvine, Irvine, CA 92697, USA.
Department of Neurobiology and Behavior, School of Biological Sciences, University of California Irvine, Irvine, CA 92697, USA.
Int J Mol Sci. 2018 Jan 14;19(1):242. doi: 10.3390/ijms19010242.
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 ( and , respectively), , , superoxide dismutases (, , and ) and catalase (), and analyzed their associated melanoma risk. Five SNPs, namely rs1049255 (), rs4673 (), rs10951982 (), rs8031 (), and rs2536512 (), exhibited significant genotypic frequency differences between melanoma cases and healthy controls. In simple logistic regression, rs10951982 (odds ratio (OR) 8.98, 95% confidence interval (CI): 5.08 to 16.44; < 0.001) reached universal significance ( = 0.002) and the minor alleles were associated with increased risk of melanoma. In contrast, minor alleles in rs8031 (OR 0.16, 95% CI: 0.06 to 0.39; < 0.001) and rs2536512 (OR 0.08, 95% CI: 0.01 to 0.31; = 0.001) were associated with reduced risk of melanoma. In multivariate logistic regression, rs10951982 (OR 6.15, 95% CI: 2.98 to 13.41; < 0.001) remained significantly associated with increased risk of melanoma. Our results highlighted the importance of , , and variants in the risk of melanoma.
最近的研究表明，紫外线（UV）诱导的黑色素碎片化学激发会导致 DNA 损伤；而黑色素碎片的化学激发需要活性氧（ROS），因为 ROS 会激发黑色素碎片中的一个电子。此外，ROS 本身也会导致 DNA 损伤。我们假设 ROS 产生和代谢酶是 UV 驱动黑色素瘤的主要贡献者。在这项针对 349 名参与者的病例对照研究中，我们对烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶 1 和 4（和，分别）、、、超氧化物歧化酶（、、和）和过氧化氢酶（）中的 23 个优先单核苷酸多态性（SNP）进行了基因分型，并分析了它们与黑色素瘤风险的相关性。五个 SNP，即 rs1049255（）、rs4673（）、rs10951982（）、rs8031（）和 rs2536512（），在黑色素瘤病例和健康对照组之间表现出显著的基因型频率差异。在简单的逻辑回归中，rs10951982（比值比（OR）8.98，95%置信区间（CI）：5.08 至 16.44；<0.001）达到普遍意义（=0.002），并且次要等位基因与黑色素瘤风险增加相关。相比之下，rs8031（OR 0.16，95%CI：0.06 至 0.39；<0.001）和 rs2536512（OR 0.08，95%CI：0.01 至 0.31；=0.001）中的次要等位基因与黑色素瘤风险降低相关。在多变量逻辑回归中，rs10951982（OR 6.15，95%CI：2.98 至 13.41；<0.001）仍然与黑色素瘤风险增加显著相关。我们的结果强调了、、和变体在黑色素瘤风险中的重要性。
