Wang Sophia S, Vajdic Claire M, Linet Martha S, Slager Susan L, Voutsinas Jenna, Nieters Alexandra, de Sanjose Silvia, Cozen Wendy, Alarcón Graciela S, Martinez-Maza Otoniel, Brown Elizabeth E, Bracci Paige M, Lightfoot Tracy, Turner Jennifer, Hjalgrim Henrik, Spinelli John J, Zheng Tongzhang, Morton Lindsay M, Birmann Brenda M, Flowers Christopher R, Paltiel Ora, Becker Nikolaus, Holly Elizabeth A, Kane Eleanor, Weisenburger Dennis, Maynadie Marc, Cocco Pierluigi, Foretova Lenka, Staines Anthony, Davis Scott, Severson Richard, Cerhan James R, Breen Elizabeth C, Lan Qing, Brooks-Wilson Angela, De Roos Anneclaire J, Smith Martyn T, Roman Eve, Boffetta Paolo, Kricker Anne, Zhang Yawei, Skibola Christine, Chanock Stephen J, Rothman Nathaniel, Benavente Yolanda, Hartge Patricia, Smedby Karin E
Am J Epidemiol. 2015 Mar 15;181(6):406-21. doi: 10.1093/aje/kwu290. Epub 2015 Feb 23.
Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).
自身免疫性疾病和免疫系统相关的基因变异与非霍奇金淋巴瘤（NHL）的风险相关。在国际淋巴瘤流行病学联盟开展的14项研究（1988 - 2007年）对8692例NHL病例和9260例对照进行的汇总分析中，我们评估了免疫系统基因变异与自身免疫性疾病在NHL风险中的相互作用。我们评估了与免疫相关的单核苷酸多态性rs1800629（肿瘤坏死因子基因（TNF）G308A）、rs1800890（白细胞介素 - 10基因（IL10）T3575A）、rs6457327（人类白细胞抗原基因（HLA）I类）、rs10484561（HLA II类）和rs2647012（HLA II类），并将自身免疫性疾病分类为主要由B细胞或T细胞反应介导。我们构建了无条件逻辑回归模型，以通过基因型分层来衡量自身免疫性疾病与NHL之间的关联。由B细胞反应介导的自身免疫性疾病与NHL风险增加相关，特别是弥漫性大B细胞淋巴瘤（优势比（OR）= 3.11，95%置信区间（CI）：2.25，4.30）和边缘区淋巴瘤（OR = 5.80，95%CI：3.82，8.80）；由T细胞反应介导的自身免疫性疾病与外周T细胞淋巴瘤相关（OR = 2.14，95%CI：1.35，3.38）。在存在rs1800629 AG/AA基因型的情况下，与GG基因型（OR = 1.82，95%CI：1.31，2.53）相比，B细胞介导的自身免疫性疾病增加了NHL风险（OR = 3.27，95%CI：2.07，5.16；P相互作用 = 0.03）。这种相互作用在主要的B细胞NHL亚型中是一致的，包括边缘区淋巴瘤（P相互作用 = 0.02）和滤泡性淋巴瘤（P相互作用 = 0.04）。
