Tumor Necrosis Factor (TNF) and Lymphotoxin-α (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium
Tumor Necrosis Factor (TNF) and Lymphotoxin-α (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium
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DOI：
10.1093/aje/kwp383
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发表时间：
2010-02-01
影响因子：
5
通讯作者：
Wang, Sophia S.
中科院分区：
文献类型：
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作者：
Skibola, Christine F.;Bracci, Paige M.;Wang, Sophia S.
在一项国际淋巴瘤流行病学联盟的汇总分析中，肿瘤坏死因子（TNF）和白细胞介素-10 （IL10）这两个免疫系统相关基因的多态性与非霍奇金淋巴瘤（NHL）的风险相关。本研究将8,847名参与者添加到先前的数据中（1989年至2005年在14例病例对照研究中诊断的患者；7,999例病例，8,452例对照），以检测TNF -308G > A （rs1800629）、淋巴素α (LTA) 252A > G （rs909253）、IL10 -3575T > A （rs1800890、rs1800896）和含有2 (NOD2) 3020insC （rs2066847）基因的多态性。使用双侧检验估计非西班牙裔白人和几个种族亚组的优势比。与先前的研究结果一致，“新”参与者TNF -308A携带者的优势比增加(NHL：每等位基因优势比(ORallelic) = 1.10， p趋势= 0.001；弥漫性大b细胞淋巴瘤（DLBCL）： ORallelic = 1.23, P-trend = 0.004。在联合人群中，TNF -308A携带者的优势比增加(NHL: ORallelic = 1.13, P-trend = 0.0001; DLBCL: ORallelic = 1.25, P-trend = 3.7 × 10(-6)；边缘带淋巴瘤：ORallelic = 1.35, P-trend = 0.004)和lta252g携带者（DLBCL: ORallelic = 1.12, P-trend = 0.006；真菌样霉菌病：ORallelic = 1.44, P-trend = 0.015）。含有LTA/TNF变异等位基因的LTA 252A > G/TNF -308G > A单倍型与DLBCL密切相关（P = 2.9 × 10(-8)）。结果提示IL10 - 3575t> A与DLBCL （P-trend = 0.02）、IL10 -1082A > G与套细胞淋巴瘤（P-trend = 0.04）相关。这些发现加强了先前关于DLBCL和LTA 252A > G/TNF -308A位点的研究结果，并提供了强有力的证据，证明这些TNF/LTA基因变异或其他连锁不平衡的基因变异与NHL病因有关。
In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G > A (rs1800629), lymphotoxin-alpha (LTA) 252A > G (rs909253), IL10 -3575T > A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, P-trend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, P-trend = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: ORallelic = 1.13, P-trend = 0.0001; DLBCL: ORallelic = 1.25, P-trend = 3.7 x 10(-6); marginal zone lymphoma: ORallelic = 1.35, P-trend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, P-trend = 0.006; mycosis fungoides: ORallelic = 1.44, P-trend = 0.015). The LTA 252A > G/TNF -308G > A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T > A and DLBCL (P-trend = 0.02) and IL10 -1082A > G and mantle cell lymphoma (P-trend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A > G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.