Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Haematologica. 2010 Aug;95(8):1405-14. doi: 10.3324/haematol.2010.022095. Epub 2010 May 29.
To evaluate the contribution of candidate gene association studies to the understanding of genetic susceptibility to childhood acute lymphoblastic leukemia we conducted a systematic review and meta-analysis of published studies (January 1996-July 2009). Studies had to meet the following criteria: be case-control design, be studied by two or more studies, not be focused on HLA antigen genetic markers and be published in English. We identified 47 studies of polymorphic variation in 16 genes and acute lymphoblastic leukemia risk. To clarify the impact of individual polymorphisms on risk, pooled analyses were performed. Of the 25 polymorphic variants studied, significant associations (P<0.05) were seen in pooled analyses for eight variants: GSTM1 (OR =1.16; 95%CI: 1.04-1.30), MTRR A66G (OR=0.73, 95%CI:0.59-0.91), SHMT1 C1420T (OR=0.79, 95%CI: 0.65-0.98), RFC1 G80A (OR=1.37, 95%CI: 1.11-1.69), CYP1A1*2A (OR=1.36, 95%CI:1.11-1.66), CYP2E1*5B (OR=1.99, 95%CI:1.32-3.00) NQO1 C609T (OR=1.24, 95%CI:1.02-1.50) and XRCC1 G28152A (OR=1.78, 95%CI:1.32-2.42). These findings should, however, be interpreted with caution as the estimated false-positive report probabilities (FPRP) for each association were not noteworthy (i.e. FPRP>0.2). While candidate gene analyses are complementary to genome-wide association studies, future analyses should be based on sample sizes commensurate with the detection of small effects and attention needs to be paid to study design.
为了评估候选基因关联研究对儿童急性淋巴细胞白血病遗传易感性的贡献，我们对已发表的研究进行了系统的综述和荟萃分析（1996 年 1 月至 2009 年 7 月）。研究必须符合以下标准：病例对照设计，由两项或更多研究进行，不专注于 HLA 抗原遗传标记，用英文发表。我们共确定了 47 项关于 16 个基因和急性淋巴细胞白血病风险的多态性变异的研究。为了阐明个体多态性对风险的影响，我们进行了合并分析。在所研究的 25 个多态性变异中，有 8 个变异在合并分析中具有显著相关性（P<0.05）：GSTM1（OR=1.16；95%CI：1.04-1.30）、MTRR A66G（OR=0.73，95%CI：0.59-0.91）、SHMT1 C1420T（OR=0.79，95%CI：0.65-0.98）、RFC1 G80A（OR=1.37，95%CI：1.11-1.69）、CYP1A1*2A（OR=1.36，95%CI：1.11-1.66）、CYP2E1*5B（OR=1.99，95%CI：1.32-3.00）、NQO1 C609T（OR=1.24，95%CI：1.02-1.50）和 XRCC1 G28152A（OR=1.78，95%CI：1.32-2.42）。然而，由于每个关联的估计假阳性报告概率（FPRP）并不显著（即 FPRP>0.2），因此应谨慎解释这些发现。虽然候选基因分析是全基因组关联研究的补充，但未来的分析应基于与检测小效应相称的样本量，并且需要注意研究设计。
