Pediatric Clinics, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen, Denmark.
Leukemia. 2012 Apr;26(4):675-81. doi: 10.1038/leu.2011.274. Epub 2011 Oct 18.
Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk of developing ALL. This international collaboration identified 54 sibships with two (N = 51) or more (N = 3) cases of childhood ALL (ages <18 years). The 5-year event-free survival for 61 patients diagnosed after 1 January 1990 was 0.83 ± 0.05. Ages at diagnosis (Spearman correlation coefficient, r(S) = 0.41, P = 0.002) were significantly correlated, but not WBCs (r(S) = 0.23, P = 0.11). In 18 sibships with successful karyotyping in both cases, six were concordant for high-hyperdiploidy (N = 3), t(12;21) [ETV6/RUNX1] (N = 1), MLL rearrangement (N = 1) or t(1;19)(q23/p13) (N = 1). Eleven sibships were ALL-subtype concordant, being T-cell ALL (T-ALL) (N = 5, of a total of six sibships, where the first-born had T-ALL) or B-lineage ALL belonging to the same cytogenetic subset (N = 6), a finding that differs significantly from the expected chance distribution (κ: 0.58; P < 0.0001). These data indicate strong genetic and/or environmental risk factors for childhood ALL that are restricted to specific ALL subtypes, which must be taken into account, when performing epidemiological studies to reveal etiological factors.
多态基因与急性淋巴细胞白血病 (ALL) 的风险有关。儿童期早期感染负担低的替代标志物也与儿童 ALL 发病风险增加有关。目前尚不确定 ALL 患儿的同胞是否具有更高的 ALL 发病风险。本国际合作研究共确定了 54 个同胞家庭，其中有 2 例（N = 51）或 2 例以上（N = 3）儿童 ALL（年龄 <18 岁）。1990 年 1 月 1 日后诊断的 61 例患者的 5 年无事件生存率为 0.83 ± 0.05。诊断时的年龄（Spearman 相关系数 r(S) = 0.41，P = 0.002）显著相关，但白细胞计数（r(S) = 0.23，P = 0.11）无关。在 18 个病例均成功进行核型分析的同胞家庭中，6 个家庭的病例均为高倍体性（N = 3）、t(12;21) [ETV6/RUNX1]（N = 1）、MLL 重排（N = 1）或 t(1;19)(q23/p13)（N = 1）。11 个同胞家庭 ALL 亚型一致，均为 T 细胞 ALL（T-ALL）（N = 5，在总共 6 个同胞家庭中，第一个发病的为 T-ALL）或 B 细胞 ALL，属于同一细胞遗传学亚组（N = 6），这一发现与预期的随机分布显著不同（κ：0.58；P < 0.0001）。这些数据表明，儿童 ALL 存在特定的遗传和/或环境危险因素，且这些危险因素仅限于特定的 ALL 亚型，在进行流行病学研究以揭示病因因素时必须考虑到这些因素。
