A Case-Control Study of the Genetic Variability in Reactive Oxygen Species-Metabolizing Enzymes in Melanoma Risk.
A Case-Control Study of the Genetic Variability in Reactive Oxygen Species-Metabolizing Enzymes in Melanoma Risk.
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DOI：
10.3390/ijms19010242
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发表时间：
2018-01-14
影响因子：
5.6
通讯作者：
Liu-Smith F
中科院分区：
文献类型：
--
作者：
Yuan TA;Yourk V;Farhat A;Ziogas A;Meyskens FL;Anton-Culver H;Liu-Smith F
最近的研究表明，紫外线（UV）诱导的黑色素片段的化学激发导致DNA损伤；黑色素片段的化学激发需要活性氧（ROS），因为ROS激发黑色素片段中的电子。此外，ROS本身也会造成DNA损伤。我们假设ROS产生和代谢酶是紫外线驱动的黑色素瘤的主要贡献者。在这项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（分别为NOX1和NOX4）、CYBA、RAC1、超氧化物歧化酶（SOD1、SOD2和SOD3）和过氧化氢酶（CAT）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的相关风险。5个snp分别为rs1049255 （CYBA）、rs4673 （CYBA）、rs10951982 （RAC1）、rs8031 （SOD2）和rs2536512 (SOD3)，在黑色素瘤病例和健康对照中表现出显著的基因型频率差异。在简单逻辑回归中，RAC1 rs10951982(优势比（OR） 8.98, 95%可信区间（CI）： 5.08 ~ 16.44；P < 0.001)达到普遍意义（P = 0.002），次要等位基因与黑色素瘤风险增加相关。相比之下，SOD2 rs8031 （OR 0.16, 95% CI: 0.06至0.39;p < 0.001）和SOD3 rs2536512 （OR 0.08, 95% CI: 0.01至0.31;p = 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logistic回归中，RAC1 rs10951982 （OR 6.15, 95% CI: 2.98 ~ 13.41; p < 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RAC1、SOD2和SOD3变异在黑色素瘤风险中的重要性。
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.
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