Genetic markers of pigmentation are novel risk loci for uveal melanoma
Genetic markers of pigmentation are novel risk loci for uveal melanoma
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DOI：
10.1038/srep31191
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发表时间：
2016-08-08
影响因子：
4.6
通讯作者：
Kirchhoff, Tomas
中科院分区：
文献类型：
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作者：
Ferguson, Robert;Vogelsang, Matjaz;Kirchhoff, Tomas
虽然遗传危险因素在葡萄膜黑色素瘤(UM)病因学中的作用已被强烈建议，但UM的遗传易感性目前仍未得到深入研究。由于皮肤黑色素瘤(CM)和皮肤黑色素瘤(UM)具有共同的流行病学危险因素，在本研究中，我们选择了28个SNPs，这些SNP在之前关于CM或CM相关宿主表型(如色素沉着和眼睛颜色)的全基因组关联研究中被确定为风险变异，并测试它们与UM风险的相关性。通过对272例UM患者和1782例对照的加性模型的Logistic回归分析，我们发现了5个与UM风险显著相关的变异，均通过了多重检验的调整。Rs12913832(OR=0.529，95%CI 0.415-0.673；p=8.47E-08)、rs1129038(OR=0.533，95%CI 0.419-0.678；p=1.19E-07)和rs916977(OR=0.465，95%CI 0.339-0.637；p=3.04E-07)在HERC2/OCA2区域的15q12上相关(r(2)>；0.5)和MAP，这决定了人类群体中的眼睛颜色。我们的数据首次证明，与色素沉着特征相关的遗传因素是UM易感性的危险基因。
While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR=0.529, 95% CI 0.415-0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.