Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project
Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project
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DOI：
10.1093/jncimonographs/lgu013
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发表时间：
2014-01-01
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影响因子：
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通讯作者：
Sampson, Joshua N.
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文献类型：
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作者：
Morton, Lindsay M.;Slager, Susan L.;Sampson, Joshua N.
背景非霍奇金淋巴瘤（NHL）包括生物学和临床异质性亚型。在此之前，研究规模有限的能力，比较和对比这些异质subtype.Methods的风险因素配置文件，我们汇集了个人水平的数据，从17 471 NHL病例和23 096控制在20个病例对照研究，从国际淋巴瘤流行病学联盟（InterLymph）。我们估计了11种NHL亚型与自我报告的病史、恶性血液病家族史、生活方式因素和职业之间的相关性，并测量了比值比。然后，我们通过评估亚型之间给定暴露的估计比值比的变异性（Q值）来评估相关性的异质性。最后，我们将亚型组织成一个层次树，以确定具有相似风险因素特征的组。结果NHL各亚型间病史因素的危险性差异有统计学意义（自身免疫性疾病、丙型肝炎病毒血清阳性、湿疹和输血）、白血病和多发性骨髓瘤家族史、饮酒、吸烟和某些职业，而在NHL家族史、休闲性日光暴露、花粉热、过敏和社会经济地位方面，观察到亚型之间的风险大致相同。总体而言，T细胞和B细胞淋巴瘤之间的风险因素差异最大（P-NODE < 1.0 x 10（-4）），风险增加通常限于湿疹，T细胞活化自身免疫性疾病，多发性骨髓瘤家族史和画家职业的T细胞淋巴瘤。我们进一步观察到B细胞淋巴瘤之间的显著异质性（P-NODE < 1.0 x 10（-4））。B细胞激活性自身免疫性疾病和丙型肝炎病毒血清阳性的风险增加，饮酒和教师职业的风险降低，一般仅限于边缘区淋巴瘤，伯基特/伯基特样淋巴瘤/白血病，弥漫性大B细胞淋巴瘤和/或淋巴浆细胞淋巴瘤/瓦尔登斯特伦巨球蛋白血症。我们确定了亚型之间共同的风险因素以及在个体或少数亚型之间似乎不同的风险因素，这表明亚型特异性和共享的潜在机制。需要进一步的研究来测试假定的机制，调查其他风险因素（例如，其他感染，环境暴露和饮食），并评估与遗传易感性的潜在联合效应。
Background Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.Methods We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P-NODE).Results Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P-NODE < 1.0 x 10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P-NODE < 1.0 x 10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia.Conclusions Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.