Pei Jen-Sheng, Hsu Chin-Mu, Tsai Chia-Wen, Chang Wen-Shin, Ji Hong-Xue, Hsiao Chieh-Lun, Miao Chia-En, Hsu Yuan-Nian, Bau Da-Tian
Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, ROC.
Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, ROC.
PLoS One. 2015 Mar 20;10(3):e0119776. doi: 10.1371/journal.pone.0119776. eCollection 2015.
Acute lymphoblastic leukemia (ALL) is the most prevalent type of pediatric cancer, the causes of which are likely to involve an interaction between genetic and environmental factors. To evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) on childhood ALL risk in Taiwan, two well-known polymorphic genotypes of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed to examine the extent of their associations with childhood ALL susceptibility and to discuss the MTHFR genotypic contribution to childhood ALL risk among different populations.
METHODOLOGY/PRINCIPAL FINDINGS: In total, 266 patients with childhood ALL and an equal number of non-cancer controls recruited were genotyped utilizing PCR-RFLP methodology. The MTHFR C677T genotype, but not the A1298C, was differently distributed between childhood ALL and control groups. The CT and TT of MTHFR C677T genotypes were significantly more frequently found in controls than in childhood ALL patients (odds ratios=0.60 and 0.48, 95% confidence intervals=0.42-0.87 and 0.24-0.97, respectively). As for gender, the boys carrying the MTHFR C677T CT or TT genotype conferred a lower odds ratio of 0.51 (95% confidence interval=0.32-0.81, P=0.0113) for childhood ALL. As for age, those equal to or greater than 3.5 years of age at onset of disease carrying the MTHFR C677T CT or TT genotype were of lower risk (odds ratio= 0.43 and 95% confidence interval=0.26-0.71, P=0.0016).
Our results indicated that the MTHFR C677T T allele was a protective biomarker for childhood ALL in Taiwan, and the association was more significant in male patients and in patients 3.5 years of age or older at onset of disease.
急性淋巴细胞白血病(ALL)是最常见的儿童癌症类型,其病因可能涉及遗传和环境因素之间的相互作用。为了评估亚甲基四氢叶酸还原酶(MTHFR)基因多态性对台湾儿童ALL风险的影响,分析了两种著名的MTHFR基因多态性基因型,即C677T(rs1801133)和A1298C(rs1801131),以研究它们与儿童ALL易感性的关联程度,并探讨MTHFR基因多态性对不同人群中儿童ALL风险的贡献。
方法/主要发现:总共对266例儿童ALL患者和数量相等的非癌症对照者采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行基因分型。MTHFR C677T基因型,而非A1298C基因型,在儿童ALL组和对照组之间的分布存在差异。MTHFR C677T基因型的CT和TT在对照组中的出现频率显著高于儿童ALL患者(优势比分别为0.60和0.48,95%置信区间分别为0.42 - 0.87和0.24 - 0.97)。就性别而言,携带MTHFR C677T CT或TT基因型的男孩患儿童ALL的优势比为0.51(95%置信区间 = 0.32 - 0.81,P = 0.0113)。就年龄而言,疾病发病时年龄等于或大于3.5岁且携带MTHFR C677T CT或TT基因型的患者风险较低(优势比 = 0.43,95%置信区间 = 0.26 - 0.71,P = 0.0016)。
我们的结果表明,MTHFR C677T的T等位基因是台湾儿童ALL的一种保护性生物标志物,且这种关联在男性患者以及疾病发病时年龄为3.5岁或以上的患者中更为显著。