Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24 577 first-degree relatives of 11 039 patients with myeloproliferative neoplasms in Sweden
Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24 577 first-degree relatives of 11 039 patients with myeloproliferative neoplasms in Sweden
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DOI：
10.1182/blood-2008-03-143602
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发表时间：
2008-09-15
期刊：
影响因子：
20.3
通讯作者：
Bjorkholm, Magnus
中科院分区：
文献类型：
--
作者：
Landgren, Ola;Goldin, Lynn R.;Bjorkholm, Magnus
以前的小型研究已经报道了骨髓增生性肿瘤(MPN)的家族聚集性，包括真性红细胞增多症(PV)、原发性血小板增多症(ET)和骨髓纤维化(MF)。我们确定了瑞典确诊的6217例PV、2838例ET、1172例MF和812例MPN无法分类(NOS)患者，43550名对照，以及病例(n=24577)和对照(n=99542)的一级亲属。使用边际生存模型，我们计算了相对风险(RR)和95%的可信区间作为家庭聚集性的衡量标准。MPN患者亲属患PV(RR=5.7；3.5~9.1)、ET(RR=7.4；3.7~14.8)和MPN NOS(RR=7.5；2.7~20.8)的风险显著增加。按一级亲属类型分层的分析显示，兄弟姐妹的风险一直较高，符合隐性遗传模型，只有确定易感基因才能证实这一点(S)。MPN患者亲属诊断MPN时的平均年龄(57.5岁)与对照组(60.6岁)无差异(P=0.20)，MPN患者父母与子女的年龄差异无统计学意义(P=0.10)，不支持预期。MPN患者的亲属患慢性髓系白血病的风险略有增加(CML；RR=1.9；0.9-3.8；P=0.09)。我们的发现在MPN患者的一级亲属中MPN的风险增加了5-7倍，支持了这样的假设，即共同的、强大的、共同的易感基因容易患上PV、ET、MF，甚至可能是CML。
Previous small studies have reported familial clustering of myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). We identified 6217 PV, 2838 ET, 1172 MF, and 812 MPN unclassifiable (NOS) patients diagnosed in Sweden, 43 550 controls, and first-degree relatives of cases (n = 24 577) and controls (n = 99 542). Using a marginal survival model, we calculated relative risks (RRs) and 95% confidence intervals as measures of familial aggregation. Relatives of MPN patients had significantly increased risks of PV (RR = 5.7; 3.5-9.1), ET (RR = 7.4; 3.7-14.8), and MPN NOS (RR = 7.5; 2.7-20.8). Analyses stratified by type of first-degree relative revealed consistently higher risks for siblings, compatible with a model of recessive genetic inheritance, which can be confirmed only by identifying the susceptibility gene(s). Mean age at MPN diagnosis was not different (P = .20) for affected relatives of cases (57.5 years) versus controls (60.6 years), and risk of MPN by age was not different for parents versus offspring of MPN cases (P=.10), providing no support for anticipation. Relatives of MPN patients had a borderline increased risk of chronic myeloid leukemia (CML; RR = 1.9; 0.9-3.8; P=.09). Our findings of 5-to 7-fold elevated risk of MPNs among first-degree relatives of MPN patients support the hypothesis that common, strong, shared susceptibility genes predispose to PV, ET, MF, and possibly CML.