Cytokine polymorphisms in the Tb1/Th2 pathway and susceptibility to non-Hodgkin lymphoma
Cytokine polymorphisms in the Tb1/Th2 pathway and susceptibility to non-Hodgkin lymphoma
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DOI：
10.1182/blood-2005-10-4160
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发表时间：
2006-05-15
期刊：
影响因子：
20.3
通讯作者：
Chanock, Stephen
中科院分区：
文献类型：
--
作者：
Lan, Qing;Zheng, Tongzhang;Chanock, Stephen
研究表明，Th1和Th2细胞因子基因的常见多态性可以改变基因表达，调节Th1/Th2应答之间的平衡，并影响自身免疫性疾病、感染性疾病和癌症的易感性。在康涅狄格州女性非霍奇金淋巴瘤(NHL；n=518例，597例对照)的人群病例对照研究中，我们分析了20个候选Th1/Th2基因的一个或多个单核苷酸多态(SNPs)。关键基因IL4、IL5、IL6和100中的SNP与NHL的风险相关，在某些情况下还与特定的组织亚型相关。对IL10启动子的4个SNP(-3575T>；A、-1082A>；G、-819C>；T和-592C>；A)的分析表明，AGCC单倍型(优势比[OR]=1.54，95%可信区间[CI]=1.21-1.96，P<；001)和TATA单倍型(OR=1.37，95%CI=1.05-1.79，P=.02)都与B细胞淋巴瘤的风险增加相关。相反，IL4-1098G等位基因与T细胞淋巴瘤的风险增加相关(OR=3.84；95%C_1=1.79-8.22；P<；.001)。此外，在对多重比较进行调整后，IL10和IL4 SNP相关性仍然显著。提示Th2细胞因子基因SNPs可能与非霍奇金淋巴瘤的发病风险有关。
Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in critical genes, IL4, IL5, IL6, and 100, were associated with risk for NHL and in some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10 promoter (-3575T > A, -1082A > G, -819C > T, and -592C > A) revealed that both the AGCC haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P < .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% C1 = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained significant after adjusting for multiple comparisons. These results suggest that SNPs in Th2 cytokine genes may be associated with risk of NHL.