Flap Endonuclease 1 基因型与儿童白血病风险的关联。

The Association of Flap Endonuclease 1 Genotypes with the Risk of Childhood Leukemia.

机构信息

Departments of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.

Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.

出版信息

Cancer Genomics Proteomics. 2016 Jan-Feb;13(1):69-74.

PMID:26708601

Abstract

AIM

Flap endonuclease 1 (FEN1) is one of the most important proteins in maintaining genome stability and preventing carcinogenesis. In recent years, the contribution of two variants of FEN1, rs174538 and rs4246215, regarding cancer risk have been investigated in lung, breast, liver, esophageal, gastric, colorectal cancer and glioma. However, it has not been revealed whether rs174538 and rs4246215 are associated with leukemia. Therefore, in the present study we aimed to evaluate the contribution of these genotypic polymorphisms in FEN1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan.

MATERIALS AND METHODS

In total, 266 patients with childhood ALL and an equal number of recruited non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTS

The FEN1 rs174538 genotype, but not rs4246215, was differently distributed between childhood ALL and control groups. The AG and AA of FEN1 rs174538 genotypes were significantly less frequently found in childhood ALL patients than in controls (odds ratio [OR]=0.68 and 0.48, 95%confidence intervals [CI]=0.47-0.98 and 0.24-0.82, respectively). As for gender, boys carrying the FEN1 rs174538 AG or AA genotype conferred lower ORs of 0.55 and 0.36 (95%CI=0.33-0.91 and 0.18-0.73, p=0.0053) for childhood ALL. Regarding age, those equal to or greater than 3.5 years of age at onset carrying the FEN1 rs174538 AG or AA genotype were of lower risk (ORs=0.53 and 0.32, 95%CI=0.31-0.90 and 0.15-0.70, p=0.0042).

CONCLUSION

The FEN1 rs174538 A allele is a protective biomarker for childhood ALL and this association is more significant in males and in patients at onset age of 3.5 years or older.

摘要

目的

核酸内切酶 1（FEN1）是维持基因组稳定性和预防致癌作用的最重要的蛋白质之一。近年来，研究人员研究了 FEN1 的两个变体 rs174538 和 rs4246215 对肺癌、乳腺癌、肝癌、食管癌、胃癌、结直肠癌和神经胶质瘤的癌症风险的贡献。然而，尚未揭示 rs174538 和 rs4246215 是否与白血病有关。因此，在本研究中，我们旨在评估 FEN1 中这些基因型多态性对台湾儿童急性淋巴细胞白血病（ALL）风险的影响。

材料与方法

共 266 例儿童 ALL 患者和相同数量的非癌症对照者通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。

结果

FEN1 rs174538 基因型而非 rs4246215 基因型在儿童 ALL 组和对照组之间的分布不同。FEN1 rs174538 基因型的 AG 和 AA 等位基因在儿童 ALL 患者中明显少于对照组（比值比[OR]为 0.68 和 0.48，95%置信区间[CI]为 0.47-0.98 和 0.24-0.82）。就性别而言，携带 FEN1 rs174538 AG 或 AA 基因型的男孩患儿童 ALL 的比值比（OR）分别为 0.55 和 0.36（95%CI 为 0.33-0.91 和 0.18-0.73，p=0.0053）。就年龄而言，发病年龄等于或大于 3.5 岁的患者携带 FEN1 rs174538 AG 或 AA 基因型的风险较低（ORs 分别为 0.53 和 0.32，95%CI 分别为 0.31-0.90 和 0.15-0.70，p=0.0042）。