Abstract:
Although substantial advances in the identification of cytogenomic subtypes of childhood acute lymphoblastic leukemia (ALL) have been made in recent decades, epidemiologic research characterizing the etiologic heterogeneity of ALL by subtype has not kept pace. The purpose of this review is to summarize the current literature concerning subtype-specific epidemiologic risk factor associations with ALL subtype defined by immunophenotype (e.g., B-cell vs. T-cell) and cytogenomics (including gross chromosomal events characterized by recurring numerical and structural abnormalities, along with cryptic balanced rearrangements, and focal gene deletions). In case-control analyses investigating nongenetic risk factors, home paint exposure is associated with hyperdiploid, MLL-rearranged, and ETV6-RUNX1 subtypes, yet there are few differences in risk factor associations between T- and B-ALL. Although the association between maternal smoking and ALL overall has been null, maternal smoking is associated with an increasing number of gene deletions among cases. GWAS-identified variants in ARID5B have been the most extensively studied and are strongly associated with hyperdiploid B-ALL. GATA3 single nucleotide variant rs3824662 shows a strong association with Ph-like ALL (OR = 3.14). However, there have been relatively few population-based studies of adequate sample size to uncover risk factors that may define etiologic heterogeneity between and within the currently defined cytogenomic ALL subtypes.
摘要:
尽管近几十年来儿童急性淋巴细胞白血病(ALL)的细胞基因组亚型的鉴定取得了重大进展,按亚型划分ALL病因异质性的流行病学研究未能跟上步伐.这篇综述的目的是总结目前有关亚型特异性流行病学危险因素与由免疫表型定义的ALL亚型相关的文献(例如,B细胞vs.T细胞)和细胞基因组学(包括以反复出现的数字和结构异常为特征的总体染色体事件,伴随着神秘的平衡重组,和局灶性基因缺失)。在调查非遗传危险因素的病例对照分析中,家庭油漆暴露与超二倍体有关,MLL-重新排列,和ETV6-RUNX1亚型,然而,T-和B-ALL之间的危险因素关联几乎没有差异。尽管产妇吸烟和ALL总体之间的关联是零的,母亲吸烟与病例中基因缺失数量的增加有关。ARID5B中GWAS鉴定的变体已被最广泛地研究,并且与超二倍体B-ALL密切相关。GATA3单核苷酸变体rs3824662显示与Ph样ALL的强关联(OR=3.14)。然而,相对较少的以人群为基础的研究有足够的样本量来揭示可能定义当前定义的细胞基因组ALL亚型之间和内部的病因异质性的危险因素.