Schinasi Leah H, Brown Elizabeth E, Camp Nicola J, Wang Sophia S, Hofmann Jonathan N, Chiu Brian C, Miligi Lucia, Beane Freeman Laura E, de Sanjose Silvia, Bernstein Leslie, Monnereau Alain, Clavel Jacqueline, Tricot Guido J, Atanackovic Djordje, Cocco Pierluigi, Orsi Laurent, Dosman James A, McLaughlin John R, Purdue Mark P, Cozen Wendy, Spinelli John J, de Roos Anneclaire J
Department of Environmental and Occupational Health, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA.
Department of Pathology and Comprehensive Cancer Center, School of Medicine, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.
Br J Haematol. 2016 Oct;175(1):87-101. doi: 10.1111/bjh.14199. Epub 2016 Jun 22.
Family clusters of multiple myeloma (MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case-control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first-degree relative with a history of a lympho-haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first-degree relative with a history of non-Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11 470 controls were included. MM risk was elevated in association with having a first-degree relative with any lympho-haematapoietic cancer (Odds Ratio (OR) = 1·29, 95% Confidence Interval (CI): 1·08-1·55). The association was particularly strong for having a first-degree relative with MM (OR = 1·90, 95% CI: 1·26-2·87), especially among men (OR = 4·13, 95% CI: 2·17-7·85) and African Americans (OR = 5·52, 95% CI: 1·87-16·27).These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures.
多发性骨髓瘤(MM)的家族聚集现象提示该病具有遗传性。然而,MM的遗传模式以及遗传风险因素与环境风险因素在病因学中的重要性仍不明确。我们汇总了国际多发性骨髓瘤协会11项病例对照研究的数据,以确定MM风险与有淋巴造血系统癌症病史的一级亲属之间的关联。使用经研究、性别、年龄和教育水平调整的无条件逻辑回归模型,来估计MM风险与有非霍奇金淋巴瘤、霍奇金淋巴瘤、白血病或MM病史的一级亲属之间的关联。将性别、非裔美国人种族/族裔和年龄作为效应修饰因素进行探讨。共纳入2843例病例和11470例对照。与有任何淋巴造血系统癌症的一级亲属相关联时,MM风险升高(比值比(OR)=1.29,95%置信区间(CI):1.08 - 1.55)。与有MM病史的一级亲属的关联尤为强烈(OR = 1.90,95% CI:1.26 - 2.87),尤其是在男性(OR = 4.13,95% CI:2.17 - 7.85)和非裔美国人中(OR = 5.52,95% CI:1.87 - 16.27)。这些结果支持了遗传继承在MM病因学中起作用的假说。有必要开展进一步研究以确定遗传标记与环境暴露之间的相互作用。