Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma.
Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma.
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DOI：
10.1002/humu.20803
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发表时间：
2008-12
期刊：
影响因子：
3.9
通讯作者：
Wei, Qingyi
中科院分区：
文献类型：
--
作者：
Li, Chunying;Zhao, Hui;Hu, Zhibin;Liu, Zhensheng;Wang, Li-E;Gershenwald, Jeffrey E.;Prieto, Victor G.;Lee, Jeffrey E.;Duvic, Madeleine;Grimm, Elizabeth A.;Wei, Qingyi
Caspase-8（CASP 8）和Caspase-10（CASP 10）在细胞凋亡调控中起重要作用，其功能多态性可能影响细胞凋亡和癌症风险。然而，没有报道的研究已经调查了这种多态性和皮肤黑色素瘤（CM）的风险之间的关联。在一项以医院为基础的研究中，805名非西班牙裔白色CM患者和835名年龄、性别和种族匹配的无癌症对照者，我们对CASP 8和CASP 10的三种报告的肺功能多态性进行了基因分型--CASP 8 D302 H（rs 1045485：G>C）、CASP 8 -652 6 N del（rs3834129：-/CTTACT）和CASP 10 I522 L（rs 13006529：A>T）--并评估了它们与CM风险的相关性以及与已知CM风险因素的相互作用。我们还计算了重大发现的假阳性报告概率（FPRP）。CASP 8 302 H变异基因型（DH：校正比值比[OR]，0.70 [95%置信区间（CI），0.50-0.98]; DH+HH：未校正OR，0.78 [95% CI，0.62-0.98]; FPRP，0.79）和CASP 8 - 652 6 N del变异基因型（ins/del：OR，0.74 [95%CI，0.57-0.97]; ins/del+del/del：OR，0.76 [95%CI，0.61-0.95]; FPRP，0.61）与显著低于ins/ins基因型的CM风险相关。CASP 10 522 L变异基因型与CM风险的显著改变无关。此外，与最常见的单倍型D-ins-I相比，D-del-I单倍型与CM风险显著降低相关（OR，0.52 [95%CI，0.37-0.74]; FPRP，0.116）。多因素Logistic回归分析显示CASP 8 D302 H、CASP 8 - 652 6 N del、CASP 10 I522 L是CM的独立危险因素。因此，这些CASP 8和CASP 10变异多态性可能是CM易感性的生物标志物。
Caspase-8 (CASP8) and caspase-10 (CASP10) play key roles in regulating apoptosis, and functional polymorphisms of them may alter apoptosis and cancer risk. However, no reported studies have investigated the association between such polymorphisms and the risk of cutaneous melanoma (CM). In a hospital-based study of 805 non-Hispanic white patients with CM and 835 cancer-free age- sex- and ethnicity-matched controls, we genotyped three reported putatively functional polymorphisms of CASP8 and CASP10--CASP8 D302H (rs1045485:G>C), CASP8-652 6N del (rs3834129:–/CTTACT), and CASP10 I522L (rs13006529:A>T)--and assessed their associations with risk of CM and interactions with known risk factors for CM. We also calculated the false-positive-report probability (FPRP) for significant findings. CASP8 302H variant genotypes (DH: adjusted odds ratio [OR], 0.70 [95% confidence interval (CI), 0.50-0.98]; DH+HH: unadjusted OR, 0.78 [95% CI, 0.62-0.98]; FPRP, 0.79) and CASP8 -652 6N del variant genotypes (ins/del: OR, 0.74 [95% CI, 0.57-0.97]; ins/del+del/del: OR, 0.76 [95% CI, 0.61-0.95]; FPRP, 0.61) were associated with significantly lower CM risk than were the ins/ins genotypes. The CASP10 522L variant genotypes were not associated with significantly altered CM risk. Also, the D-del-I haplotype was associated with a significantly lower CM risk (OR, 0.52 [95% CI, 0.37-0.74]; FPRP, 0.116) than was the most common haplotype, D-ins-I. Furthermore, multivariate logistic regression analysis revealed that CASP8 D302H, CASP8 -652 6N del, and CASP10 I522L were independent risk factors for CM. Therefore, these CASP8 and CASP10 variant polymorphisms may be biomarkers for susceptibility to CM.
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影响因子：
4.8
作者：
Kischkel, FC;Lawrence, DA;Ashkenazi, A
通讯作者：
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