Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
Blood. 2019 Sep 19;134(12):960-969. doi: 10.1182/blood.2019001362. Epub 2019 Aug 8.
Estimating familial cancer risks is clinically important in being able to discriminate between individuals in the population at differing risk for malignancy. To gain insight into the familial risk for the different hematological malignancies and their possible inter-relationship, we analyzed data on more than 16 million individuals from the Swedish Family-Cancer Database. After identifying 153 115 patients diagnosed with a primary hematological malignancy, we quantified familial relative risks (FRRs) by calculating standardized incident ratios (SIRs) in 391 131 of their first-degree relatives. The majority of hematological malignancies showed increased FRRs for the same tumor type, with the highest FRRs being observed for mixed cellularity Hodgkin lymphoma (SIR, 16.7), lymphoplasmacytic lymphoma (SIR, 15.8), and mantle cell lymphoma (SIR, 13.3). There was evidence for pleiotropic relationships; notably, chronic lymphocytic leukemia was associated with an elevated familial risk for other B-cell tumors and myeloproliferative neoplasms. Collectively, these data provide evidence for shared etiological factors for many hematological malignancies and provide information for identifying individuals at increased risk, as well as informing future gene discovery initiatives.
评估家族癌症风险对于能够区分人群中不同恶性肿瘤风险的个体具有重要的临床意义。为了深入了解不同血液系统恶性肿瘤的家族风险及其可能的相互关系，我们分析了来自瑞典家族癌症数据库的超过 1600 万人的数据。在确定了 153115 名原发性血液系统恶性肿瘤患者后，我们通过计算其 391131 名一级亲属的标准化发病比（SIR）来量化家族相对风险（FRR）。大多数血液系统恶性肿瘤显示出相同肿瘤类型的 FRR 增加，其中混合细胞性霍奇金淋巴瘤（SIR 为 16.7）、淋巴浆细胞淋巴瘤（SIR 为 15.8）和套细胞淋巴瘤（SIR 为 13.3）的 FRR 最高。有证据表明存在多效关系；值得注意的是，慢性淋巴细胞白血病与其他 B 细胞肿瘤和骨髓增生性肿瘤的家族性高风险相关。总的来说，这些数据为许多血液系统恶性肿瘤的共同病因提供了证据，并为识别高风险个体提供了信息，同时也为未来的基因发现计划提供了信息。
