Wiemels Joseph L, Wiencke John K, Kelsey Karl T, Moghadassi Michelle, Rice Terri, Urayama Kevin Y, Miike Rei, Wrensch Margaret
Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94143-0441, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1229-35. doi: 10.1158/1055-9965.EPI-07-0041.
Previous studies have shown that glioma patients report allergies less frequently than controls, harbor lower atopy-associated IgE levels, and harbor different frequencies of polymorphisms in the IL13 and IL4 pathways than controls. We sought to confirm this latter result and extend the analysis to IgE levels. Glioma patients (n = 456) and controls (n = 541) were genotyped for genetic variants in IL4, IL4R, and IL13 and tested for total IgE levels (n = 248 controls and 289 cases). Among Whites, IL4 and IL4R polymorphisms and haplotypes were neither significantly associated with IgE levels in controls nor associated with glioma status. IL13 R110G and C-1112T were associated with increased IgE levels in controls (P < 0.001 and P = 0.04, respectively), and IL13 C-1112T was inversely associated with case-control status (P = 0.05, test for trend in dose model). An IL4R haplotype was borderline associated with increased risk in case-control analysis [odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.0-2.3]. In addition, a rare haplotype for IL4 was associated with decreased risk (OR, 0.23; 95% CI, 0.07-0.83), and a common haplotype in IL13 was associated with decreased risk (OR, 0.73; 95% CI, 0.53-1.00). Our data provide evidence for a role of IL13 polymorphisms on IgE levels and a role for IL4, IL4R, and IL13 haplotypes on case-control status. We did not find any evidence that the interleukin (IL) polymorphisms exerted their effect on glioma risk via their effects on IgE levels. Further exploration of immune susceptibility factors, including genetics, in glioma etiology is advisable.
先前的研究表明，与对照组相比，胶质瘤患者报告过敏的频率更低，特应性相关IgE水平更低，且IL13和IL4途径中多态性的频率与对照组不同。我们试图证实后一个结果，并将分析扩展至IgE水平。对456例胶质瘤患者和541例对照者进行IL4、IL4R和IL13基因变异的基因分型，并检测总IgE水平（248例对照者和289例病例）。在白人中，IL4和IL4R多态性及单倍型在对照组中与IgE水平均无显著关联，也与胶质瘤状态无关。IL13 R110G和C -1112T与对照组IgE水平升高相关（分别为P <0.001和P = 0.04），且IL13 C -1112T与病例对照状态呈负相关（P = 0.05，剂量模型趋势检验）。在病例对照分析中，一种IL4R单倍型与风险增加存在临界关联[比值比（OR），1.5；95%置信区间（95%CI），1.0 - 2.3]。此外，一种罕见的IL4单倍型与风险降低相关（OR，0.23；95%CI，0.07 - 0.83），而IL13中一种常见单倍型与风险降低相关（OR，0.73；95%CI，0.53 - 1.00）。我们的数据为IL13多态性对IgE水平的作用以及IL4、IL4R和IL13单倍型对病例对照状态的作用提供了证据。我们未发现任何证据表明白细胞介素（IL）多态性通过对IgE水平的影响而对胶质瘤风险产生作用。建议进一步探索胶质瘤病因中包括遗传学在内的免疫易感性因素。
