Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia.
Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia.
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发表时间：
2003-08
期刊：
影响因子：
11.2
通讯作者：
Kathryn Sibley;S. Rollinson;J. Allan;Alexandra G. Smith;G. Law;P. Roddam;C. Skibola;Martyn T. Smith;G. Morgan
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作者：
Kathryn Sibley;S. Rollinson;J. Allan;Alexandra G. Smith;G. Law;P. Roddam;C. Skibola;Martyn T. Smith;G. Morgan
FAS (TNFRSF6/CD95/APO-1) 基因在许多肿瘤类型中被沉默，导致无法响应促凋亡信号。 FAS启动子是多态性的，包括-1377 bp处的G到A替换和-670 bp处的A到G替换，它们分别发生在SP1和转录1转录因子结合位点的信号转导子和激活子内。在成人急性髓系白血病 (AML) 的病例对照研究中，我们发现与 -1377 bp 位置处的杂合子 (GA) 和纯合子变异 (AA) 相关的 AML 风险显着增加（病例中为 32.3%，对照为 22.0%；优势比为 1.69；95% 置信区间为 1.32-2.16）。扩展单倍型分析显示，-1377A/-670A 单倍型与疾病显着相关（3% 与 0.5%；比值比，6.72；95% 置信区间，3.13-14.51）。这些数据表明，FAS 基因启动子的变异可能影响 FAS 基因表达并调节细胞凋亡信号，从而导致 AML 风险增加。
The FAS (TNFRSF6/CD95/APO-1) gene is silenced in many tumor types, resulting in an inability to respond to proapoptotic signals. The FAS promoter is polymorphic, including a G to A substitution at -1377 bp and an A to G substitution at -670 bp, which occur within SP1 and signal transducers and activators of transcription 1 transcription factor binding sites, respectively. In a case-control study of adult acute myeloid leukemia (AML), we show a significantly increased risk of AML associated with heterozygotes (GA) and homozygote variants (AA) at position -1377 bp (32.3% in cases versus 22.0% in controls; odds ratio, 1.69; 95% confidence interval, 1.32-2.16). Extended haplotype analysis revealed that the -1377A/-670A haplotype was significantly associated with disease (3% versus 0.5%; odds ratio, 6.72; 95% confidence interval, 3.13-14.51). These data suggest that variation in the FAS gene promoter may affect FAS gene expression and modulate apoptotic signaling, contributing to an increased risk of AML.