Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China.
Cancer Med. 2019 May;8(5):2553-2560. doi: 10.1002/cam4.2082. Epub 2019 Mar 7.
In the past decade, miR-100, miR-146a, and miR-210 were reported to be dysregulated in childhood acute lymphoblastic leukemia (ALL). However, effects of genetic variants in these three microRNAs have not been investigated in Chinese population.
In this study, we conducted a case-control study to evaluate the relationship between genetic variants in miR-100, miR-146a, and miR-210 and the risk of childhood ALL in Chinese population. Subsequently, plasma expression level of miR-100 was also detected.
We found that subjects carrying mutant homozygous TT genotype of miR-100 rs543412 had a statistically significantly decreased risk of childhood ALL (adjusted odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.55-0.97, P = 0.029). This protective effect was also observed among subjects whose parents were ever drinkers (adjusted OR = 0.53, 95% CI = 0.29-0.94), or whose living house were ever painted (adjusted OR = 0.57, 95% CI = 0.34-0.94). Besides, rs543412 variant homozygous TT had a significantly protective role in patients with childhood B-ALL. Finally, we found that expression level of miR-100 in plasma of childhood ALL cases was significantly higher than that of noncancer controls.
Our study suggested that there was significant association between the polymorphisms in miR-100 (rs543412) and decreased susceptibility to childhood ALL.
过去十年中,miR-100、miR-146a 和 miR-210 被报道在儿童急性淋巴细胞白血病(ALL)中失调。然而,这些 microRNA 中的遗传变异的影响尚未在中国人中进行研究。
在这项研究中,我们进行了病例对照研究,以评估 miR-100、miR-146a 和 miR-210 中的遗传变异与中国人群儿童 ALL 风险之间的关系。随后,还检测了 miR-100 的血浆表达水平。
我们发现,携带 miR-100 rs543412 突变纯合 TT 基因型的个体患儿童 ALL 的风险具有统计学显著降低(调整后的优势比 [OR] = 0.73,95%置信区间 [CI] = 0.55-0.97,P = 0.029)。这种保护作用也在父母曾饮酒(调整后的 OR = 0.53,95% CI = 0.29-0.94)或居住房屋曾油漆(调整后的 OR = 0.57,95% CI = 0.34-0.94)的个体中观察到。此外,rs543412 变异纯合 TT 在儿童 B-ALL 患者中具有显著的保护作用。最后,我们发现儿童 ALL 病例的血浆 miR-100 表达水平明显高于非癌症对照。
我们的研究表明,miR-100(rs543412)中的多态性与儿童 ALL 易感性降低之间存在显著关联。