MiR-196a-2 Genotypes Determine the Susceptibility and Early Onset of Childhood Acute Lymphoblastic Leukemia

Abstract

Background/Aim: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. Materials and Methods: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reactionrestriction fragment length polymorphism methodology. Results: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. Conclusion: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.Acute lymphoblastic leukemia (ALL) occurs at all ages, and is the most common type of malignancy among children worldwide. The contribution of inherited factors to ALL are largely unknown. Epidemiological casecontrol studies have revealed several biomarkers that can be used for the prediction of childhood ALL (1-10). MicroRNAs (miRNAs) are endogenous non-coding RNAs that are capable of down-regulating protein-coding genes via targeting their mRNAs, degrading mRNAs or suppressing translation (11). In 2005, Lu and his colleagues analyzed the expression profiles of 217 miRNAs in a panel of human cancers (12). The downregulation of these miRNAs was correlated with cancer developmental lineage and differentiation status (12). The differential expression of circulating miRNAs between cancer patients and healthy individuals is useful for cancer diagnosis, prognosis, and therapeutic outcomes, however, studies on the genomic levels of miRNAs are very few.In recent years, mounting evidence has shown that rs11614913 (T>C), a common variant of miR-196a-2, may play a role in the development of several cancer types, including lung (13), breast (14), gastric (15), colorectal (16) and prostate cancer (17). As for childhood ALL, there are only two published studies, showing that variant C allele contributes to an increased risk of childhood ALL in Thailand (18), and China (19). Based on this information, we firstly aimed at genotyping the miR-196a-2 rs11614913 profiles among Taiwanese children and analyzing the possibility the genotypes of miR-196a-2 rs11614913 to serve as childhood ALL predictors.

Effect of miR-196a2 rs11614913 Polymorphism on Cancer Susceptibility: Evidence From an Updated Meta-Analysis

“…From the initial search in online databases, we identified a total of 1819 initial records for miR-196a2 rs11614913 polymorphism, from which 152 articles 13 – 41 , 48 …”

Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia

“…Findings in Non-Hodgkin's lymphoma suggest that the miR-196a-2 polymorphism may increase the risk of the disease by altering the expression of mature miR-196a (48). In ALL, two studies have published that rs11614913C allele contributes to an increased risk of this disease in Thailand, and China, but another one found no association results in Taiwanese ALL cases (13,24,49). Comparing the minimum free energy for optimal secondary structures of the SNP rs11614913 in pre-miR196a-2 found no dramatic effect on its secondary structure (47).…”

Impacts of mir146a genotypes to bladder cancer risk in Taiwan

“…In recent years, investigating the expression of miRNAs, and their association with risk for various types of cancer, has become a research interest for many scientists [25][26][27][28][29][30] . Although con icting and inconsistent results were obtained, the differences in the association among studies may be due to different dietary, habits, environmental exposures, and most of all, different genetic background among the various study populations.…”

“…The genotyping of mir196a rs11614913 polymorphism was done with forward and reverse primers of 5'-CCCCTTCCCTTCTCCTCCAGATA-3' and reverse primer 5'-CGAAAACCGACTGATGTAACTCCG-3', respectively. Then, the PCR cycle was performed in a PCR Thermocycler (Bio-RAD, Hercules, CA, USA) using the following conditions: initial denaturation 94 o C for 5 min, followed by denaturation at 94 o C for bp for the heterozygous variant CT genotype, respectively 25 .…”