Cozen Wendy, Gill Parkash S, Ingles Sue Ann, Masood Rizwan, Martínez-Maza Otoniel, Cockburn Myles G, Gauderman W James, Pike Malcolm C, Bernstein Leslie, Nathwani Bharat N, Salam Muhammad T, Danley Kathleen Lackerdas, Wang Wei, Gage Julia, Gundell-Miller Susan, Mack Thomas M
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Blood. 2004 Apr 15;103(8):3216-21. doi: 10.1182/blood-2003-08-2860. Epub 2003 Dec 30.
Identical twins of young adult Hodgkin lymphoma case subjects are much more likely to develop the disease compared with fraternal twins of case subjects, suggesting a genetic determinant. Interleukin 6 (IL-6) levels are increased in patients with Hodgkin lymphoma and are correlated with a poor prognosis. We hypothesized that a heritable abnormality in IL-6 regulation may predispose to young adult Hodgkin lymphoma. We obtained blood specimens from 88 young adult Hodgkin lymphoma case subjects and their twins as well as from 87 matched control subjects. IL-6 was measured from unstimulated peripheral blood mononuclear cell (PBMC) supernatant with enzyme-linked immunosorbent assays (ELISAs) and compared by using analysis of covariance. Unaffected identical twins of case subjects (surrogate case subjects) had a 87.8% higher IL-6 level compared with matched control subjects (mean difference, +483.7 pg/mL, P =.04). Analysis of the IL-6 174G>C promoter polymorphism genotypes showed that risk decreased with an increasing number of C alleles (P =.01). The CC (low secreting) genotype was associated with a decreased risk of young adult Hodgkin lymphoma relative to the GG (high secreting) genotype (odds ratio [OR] =.29; P =.03). Risk was decreased for both nodular sclerosis and other subtypes. Persons with genetically determined lower IL-6 levels may be less susceptible to young adult Hodgkin lymphoma.
与霍奇金淋巴瘤病例受试者的异卵双胞胎相比，年轻成人霍奇金淋巴瘤病例受试者的同卵双胞胎患该病的可能性要高得多，这表明存在遗传决定因素。霍奇金淋巴瘤患者的白细胞介素6（IL-6）水平升高，且与预后不良相关。我们推测，IL-6调节的遗传性异常可能易导致年轻成人患霍奇金淋巴瘤。我们从88名年轻成人霍奇金淋巴瘤病例受试者及其双胞胎以及87名匹配的对照受试者中获取了血液样本。通过酶联免疫吸附测定（ELISA）从未经刺激的外周血单核细胞（PBMC）上清液中测量IL-6，并使用协方差分析进行比较。病例受试者的未受影响的同卵双胞胎（替代病例受试者）的IL-6水平比匹配的对照受试者高87.8%（平均差异为+483.7 pg/mL，P = 0.04）。对IL-6 174G>C启动子多态性基因型的分析表明，风险随着C等位基因数量的增加而降低（P = 0.01）。与GG（高分泌）基因型相比，CC（低分泌）基因型与年轻成人霍奇金淋巴瘤风险降低相关（优势比[OR]=0.29；P = 0.03）。结节硬化型和其他亚型的风险均降低。遗传决定的IL-6水平较低的人可能对年轻成人霍奇金淋巴瘤的易感性较低。
