Wang Sophia S, Cozen Wendy, Cerhan James R, Colt Joanne S, Morton Lindsay M, Engels Eric A, Davis Scott, Severson Richard K, Rothman Nathaniel, Chanock Stephen J, Hartge Patricia
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892-7234, USA.
Cancer Res. 2007 May 15;67(10):5042-54. doi: 10.1158/0008-5472.CAN-06-4752.
Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A, rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors for non-Hodgkin lymphoma (NHL) in a large pooled analysis. We systematically investigated the effects of other established NHL risk factors in relation to the tumor necrosis factor (TNF) G308A or interleukin 10 (IL10) T3575A genotypes. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) from 1,172 cases and 982 population-based controls in a U.S. multicenter study. We investigated NHL overall and two common subtypes [diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma]. NHL risks were increased among those with both an autoimmune condition and the TNF G308A GA/AA (OR(NHL), 2.1; 95% CI, 1.0-4.2) or the IL10 T3575A TA/AA genotype (OR(NHL), 1.6; 95% CI, 0.9-2.6) compared with individuals without an autoimmune condition and with the common TNF G308A GG or IL10 T3575A TT genotype, respectively; results were similar for DLBCL and follicular lymphoma. We found that elevated DLBCL risk associated with last-born status was more pronounced among those with TNF G308A GA/AA (OR(DLBCL), 2.7; 95% CI, 1.1-6.4) or IL10 T3575A TA/AA (OR(DLBCL), 2.9; 95% CI, 1.6-5.2). Similarly, elevated DLBCL risk associated with obesity (body mass index, > or = 35 versus <25 kg/m(2)) was observed only among those with TNF G308A GA/AA (OR(DLBCL), 2.5; 95% CI, 1.1-5.7) or IL10 T3575A TA/AA genotypes (OR(DLBCL), 2.0; 95% CI, 1.1-3.5). These exploratory results require replication but provide evidence that autoimmune conditions, late birth order, and obesity act partly through a common inflammatory pathway, posing a greater risk to individuals with variant TNF and IL10 genotypes than those with wild-type alleles.
免疫调节基因中的两种常见单核苷酸多态性（TNF G308A，rs1800629和IL10 T3575A，rs1800890）最近在一项大型汇总分析中被报告为非霍奇金淋巴瘤（NHL）的风险因素。我们系统地研究了其他已确定的NHL风险因素与肿瘤坏死因子（TNF）G308A或白细胞介素10（IL10）T3575A基因型之间的关系。在美国一项多中心研究中，我们从1172例病例和982例基于人群的对照中计算了优势比（OR）和95%置信区间（95%CI）。我们对NHL总体以及两种常见亚型[弥漫性大B细胞淋巴瘤（DLBCL）和滤泡性淋巴瘤]进行了研究。与没有自身免疫性疾病且具有常见TNF G308A GG或IL10 T3575A TT基因型的个体相比，同时患有自身免疫性疾病且具有TNF G308A GA/AA（OR（NHL），2.1；95%CI，1.0 - 4.2）或IL10 T3575A TA/AA基因型（OR（NHL），1.6；95%CI，0.9 - 2.6）的个体患NHL的风险增加；DLBCL和滤泡性淋巴瘤的结果相似。我们发现，与末胎出生状态相关的DLBCL风险升高在具有TNF G308A GA/AA（OR（DLBCL），2.7；95%CI）的个体中更为明显，1.1 - 6.4）或IL10 T3575A TA/AA（OR（DLBCL），2.9；95%CI，1.6 - 5.2）。同样，仅在具有TNF G308A GA/AA（OR（DLBCL），2.5；95%CI，1.1 - 5.7）或IL10 T3575A TA/AA基因型（OR（DLBCL），2.0；95%CI，1.1 - 3.5）的个体中观察到与肥胖相关的DLBCL风险升高（体重指数，≥35与<25 kg/m²）。这些探索性结果需要重复验证，但提供了证据表明自身免疫性疾病、出生顺序靠后和肥胖部分通过共同的炎症途径起作用，与野生型等位基因个体相比，对具有变异TNF和IL10基因型的个体构成更大风险。
