Bolufer Pascual, Barragan Eva, Collado Maria, Cervera José, López José-Antonio, Sanz Miguel A
Laboratory of Molecular Biology, Department of Medical Biopathology, Hospital Universitario La Fe, Valencia, Spain.
Leuk Res. 2006 Dec;30(12):1471-91. doi: 10.1016/j.leukres.2006.01.016. Epub 2006 Oct 4.
Recent studies have provided evidence that common genetic variations with low penetrance could account for a proportion of leukemia and could also influence disease outcome, although the results obtained are still controversial.
We reviewed 54 recent reports focused on the contribution of genetic polymorphisms to the risk of developing leukemia and to disease progression. The polymorphisms of genes encoding drug-metabolising enzymes (CYP family, NQO1, GSTT1, GSTM1, GSTP1), enzymes involved in folate metabolism (MTHFR, TYMS, SHMT1, MTRR), and DNA repair enzymes (XPD, XPG, RAD51, XRCC1, XRCC3, CHEK2, ATM) were considered in the review.
There was a good agreement on the influence of NQO12 polymorphism and those of the enzymes involved in DNA repair with the increased risk of therapy-related leukemia/myelodysplastic syndrome. Most studies found a strong association between the polymorphisms MTHFR, C677T or A1298C, and NQO12 or *3 and the risk of acute lymphoblastic leukemia (ALL). In addition, most of the studies reported an association between GSTT1 deletions and an increased risk of de novo acute myeloid leukemia. In ALL, polymorphisms in the genes of folate metabolism are associated with poor prognosis, and the 3R3R TYMS polymorphism in particular is associated with methotrexate resistance.
The reports reviewed support the hypothesis that several low-penetrance genes with multiplicative effects together with dietary effects, ambient exposition, and individual immune system responses, may account for the risk of leukaemia.
近期研究已提供证据表明，低外显率的常见基因变异可解释一部分白血病病例，并且还可能影响疾病转归，尽管所获结果仍存在争议。
我们回顾了54篇近期报告，这些报告聚焦于基因多态性对白血病发生风险及疾病进展的影响。本综述考虑了编码药物代谢酶（CYP家族、NQO1、GSTT1、GSTM1、GSTP1）、参与叶酸代谢的酶（MTHFR、TYMS、SHMT1、MTRR）以及DNA修复酶（XPD、XPG、RAD51、XRCC1、XRCC3、CHEK2、ATM）的基因多态性。
关于NQO12多态性以及参与DNA修复的酶的多态性与治疗相关白血病/骨髓增生异常综合征风险增加之间的影响，存在较好的一致性。大多数研究发现MTHFR基因多态性（C677T或A1298C）、NQO12或*3与急性淋巴细胞白血病（ALL）风险之间存在强关联。此外，大多数研究报告称GSTT1缺失与初发急性髓系白血病风险增加有关。在ALL中，叶酸代谢基因的多态性与预后不良相关，尤其是3R3R TYMS多态性与甲氨蝶呤耐药有关。
所回顾的报告支持这样一种假说，即几个具有累加效应的低外显率基因，连同饮食影响、环境暴露及个体免疫系统反应，可能解释白血病的发生风险。
