Liao Fei, Yin Dandan, Zhang Yan, Hou Qianqian, Zheng Zhaoyue, Yang Li, Shu Yang, Xu Heng, Li Yu
From the Department of Laboratory Medicine (FL, DY, QH, ZZ, LY, YS, HX), National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Thoracic Oncology and Cancer Center (YZ), West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China; and Department of Oncology (YL), The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
Medicine (Baltimore). 2016 May;95(18):e3542. doi: 10.1097/MD.0000000000003542.
Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers in the world. Several single-nucleotide polymorphisms (SNPs) locating at PIP4K2A locus were identified to be associated with ALL susceptibility through genome-wide association studies, however, followed by inconsistent reports in replication studies. In this study, we conducted a meta-analysis to investigate the association status of the top independent SNPs (rs7088318 and rs4748793) with ALL susceptibility by combining the data from 6 independent studies, totally including 3508 cases and 12,446 controls with multiethnic populations. Consistent association with ALL risk of both SNPs were observed (odds ratio [OR] 1.28 and 1.29, 95% confidence interval [CI] 1.20-1.36 and 1.19-1.40, respectively). Considering clinic characteristics, rs7088318 is more related to patients with African ancestry (OR 1.48, 95% CI 1.21-1.80) and hyperdiploid subtype (OR 1.42, 95% CI 1.25-1.61). Moreover, several SNPs (eg, rs45469096) were identified to be in high linage disequilibrium with rs7088318, and affected PIP4K2A expression in lymphocytes probably by altering the binding affinity of some transcriptional factors. In conclusion, we systematically investigated the relationship between SNPs at PIP4K2A locus and ALL susceptibility, and further found potential causal variant candidates, thus better elucidating the role of PIP4K2A gene in leukemogenesis.
急性淋巴细胞白血病（ALL）是全球最常见的儿童癌症之一。通过全基因组关联研究，已确定位于PIP4K2A基因座的几个单核苷酸多态性（SNP）与ALL易感性相关，然而，后续的重复研究报告结果并不一致。在本研究中，我们进行了一项荟萃分析，通过合并6项独立研究的数据，共纳入3508例病例和12446例多民族对照，来调查顶级独立SNP（rs7088318和rs4748793）与ALL易感性的关联状况。观察到这两个SNP与ALL风险均存在一致的关联（优势比[OR]分别为1.28和1.29，95%置信区间[CI]分别为1.20 - 1.36和1.19 - 1.40）。考虑临床特征，rs7088318与非洲血统患者（OR 1.48，95% CI 1.21 - 1.80）和超二倍体亚型（OR 1.42，95% CI 1.25 - 1.61）的相关性更强。此外，还发现几个SNP（如rs45469096）与rs7088318处于高度连锁不平衡状态，并可能通过改变某些转录因子的结合亲和力影响淋巴细胞中PIP4K2A的表达。总之，我们系统地研究了PIP4K2A基因座SNP与ALL易感性之间的关系，并进一步发现了潜在的因果变异候选基因，从而更好地阐明了PIP4K2A基因在白血病发生中的作用。
