Kane Eleanor, Skibola Christine F, Bracci Paige M, Cerhan James R, Costas Laura, Smedby Karin Ekström, Holly Elizabeth A, Maynadié Marc, Novak Anne J, Lightfoot Tracy J, Ansell Stephen M, Smith Alex G, Liebow Mark, Melbye Mads, Morton Lindsay, de Sanjosé Silvia, Slager Susan L, Wang Sophia S, Zhang Yawei, Zheng Tongzhang, Roman Eve
Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom.
Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama.
Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1061-70. doi: 10.1158/1055-9965.EPI-14-1355. Epub 2015 May 11.
Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.
Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).
Obesity (BMI ≥ 30 kg/m(2)) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02-1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27-2.94), with a RERI of 0.41 (95% CI, -0.05-0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.
Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.
Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.
肥胖与淋巴瘤发生有关，可能是通过细胞因子产生增加介导，导致慢性炎症状态。本文报道了肥胖、细胞因子多态性与特定成熟B细胞肿瘤之间的关系。
汇总了来自InterLymph联盟9项美国/欧洲研究（1988 - 2008年）的4979例病例和4752例对照的数据。对于弥漫性大B细胞淋巴瘤（DLBCL）、滤泡性淋巴瘤（FL）和慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL），采用无条件逻辑回归研究体重指数（根据自我报告的身高和体重计算）与细胞因子IL1A（rs1800587）、IL1B（rs16944，rs1143627）、IL1RN（rs454078）、IL2（rs2069762）、IL6（rs1800795，rs1800797）、IL10（rs1800890，rs1800896）、TNF（rs1800629）、LTA（rs909253）和CARD15（rs2066847）中的12种多态性的联合关联。使用交互作用引起的相对超额风险（RERI）估计BMI - 多态性交互作用效应。
肥胖（BMI≥30 kg/m²）与DLBCL风险相关[比值比（OR）= 1.33；95%置信区间（CI），1.02 - 1.73]，TNF - 308GA + AA也与DLBCL风险相关（OR = 1.24；95% CI，1.07 - 1.44）。肥胖且携带TNF - 308GA + AA的患者相对于体重正常且携带TNF - 308GG的患者，DLBCL风险增加近2倍（OR = 1.93；95% CI，1.27 - 2.94），RERI为0.41（95% CI， - 0.05 - 0.84；P交互作用 = 0.13）。对于FL和CLL/SLL，未观察到肥胖或TNF - 308GA + AA单独或联合与疾病的关联。未检测到肥胖与其他多态性之间存在交互作用的证据。
我们的结果表明，细胞因子多态性一般不会与BMI相互作用增加淋巴瘤风险，但肥胖与TNF - 308GA + AA可能相互作用增加DLBCL风险。
需要采用更好的肥胖测量方法进行研究，以进一步探究肥胖与TNF - 308G>A在淋巴瘤发病机制中的相互作用。
