Dataset Information

Carriage of NBN polymorphisms and acute leukemia risk.

ABSTRACT: BACKGROUND:Recent reports revealed a significant association of NBN polymorphisms with risk of acute leukemia among Chinese, but not among Europeans. The objective of this study was to obtain a more precise measure of acute leukemia risk associated with NBN rs1805794, rs2735383, rs709816 polymorphisms. METHODS:Using PubMed, Embase, ISI Web of Science, and the Cochrane Library databases, we undertook a systematic literature search up to September 1, 2014. Eligible studies were singled out from 31 possibly related publications by two investigators. Based on the extracted NBN genotypes, we calculated pooled odds ratios (ORs) and 95% confidence intervals (95% CI) by use of the random effects model proposed by DerSimonian and Laird. RESULTS:We finally derived 3,065 subjects for meta-analysis of rs1805794, and found that carriage of the CC genotype was associated with approximately 1.70-fold increased risk of acute leukemia (OR 1.66, 95% CI 1.17-2.36; OR 1.77, 95% CI 1.23-2.54). A 25% higher risk was also identified among the individuals with the C allele (OR 1.25, 95% CI 1.03-1.51). Among 1,553 subjects for rs2735383, no significant association was indicated in the investigated comparison models. Nor did the analysis of 1,485 samples for rs709816 suggest any noteworthy connection. CONCLUSIONS:Carriage of rs1805794 polymorphism in the NBN gene may be associated with the occurrence of acute leukemia. New clinical studies are needed to identify the genetic associations and thus facilitates an increased understanding of the molecular mechanisms of this malignancy.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4443107 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Carriage of NBN polymorphisms and acute leukemia risk.

Wang Yan Y Sun Zhongliang Z Xu Yuan Y

International journal of clinical and experimental medicine 20150315 3

<h4>Background</h4>Recent reports revealed a significant association of NBN polymorphisms with risk of acute leukemia among Chinese, but not among Europeans. The objective of this study was to obtain a more precise measure of acute leukemia risk associated with NBN rs1805794, rs2735383, rs709816 polymorphisms.<h4>Methods</h4>Using PubMed, Embase, ISI Web of Science, and the Cochrane Library databases, we undertook a systematic literature search up to September 1, 2014. Eligible studies were sing ...[more]

PMID: 26064273

Similar Datasets

Project description:BackgroundThe MRE11, RAD50, and NBN genes encode proteins of the MRE11-RAD50-NBN (MRN) complex involved in cellular response to DNA damage and the maintenance of genome stability. In our previous study we showed that the germline p.I171V mutation in NBN may be considered as a risk factor in the development of childhood acute lymphoblastic leukemia (ALL) and some specific haplotypes of that gene may be associated with childhood leukemia. These findings raise important questions about the role of mutations in others genes of the MRN complex in childhood leukemia. The aim of this study was to answer the question whether MRE11 and RAD50 alterations may be associated with childhood ALL or AML.MethodsWe estimated the frequency of constitutional mutations and polymorphisms in selected regions of MRE11, RAD50, and NBN in the group of 220 children diagnosed with childhood leukemias and controls (n=504/2200). The analysis was performed by specific amplification of region of interest by PCR and followed by multi-temperature single-strand conformation polymorphism (PCR-MSSCP) technique. We performed two molecular tests to examine any potential function of the detected the c.551+19G>A SNP in RAD50 gene. To our knowledge, this is the first analysis of the MRE11, RAD50 and NBN genes in childhood leukemia.ResultsThe frequency of either the AA genotype or A allele of RAD50_rs17166050 were significantly different in controls compared to leukemia group (ALL+AML) (p<0.0019 and p<0.0019, respectively). The cDNA analysis of AA or GA genotypes carriers has not revealed evidence of splicing abnormality of RAD50 pre-mRNA. We measured the allelic-specific expression of G and A alleles at c.551+19G>A and the statistically significant overexpression of the G allele has been observed. Additionally we confirmed the higher incidence of the p.I171V mutation in the leukemia group (7/220) than among controls (12/2400) (p<0.0001).ConclusionThe formerly reported sequence variants in the RAD50 and MRE11 gene may not constitute a risk factor of childhood ALL in Polish population. The RAD50_rs17166050 variant allele is linked to decreased ALL risk (p<0.0009, OR=0.6358 (95%CI: 0.4854-0.8327)). Despite the fact that there is no splicing abnormality in carriers of the variant allele but an excess of the G over the A allele was consistently observed. This data demonstrate that some specific alternations of the RAD50 gene may be associated with childhood ALL.

Dataset Information

Carriage of NBN polymorphisms and acute leukemia risk.

Publications

Carriage of NBN polymorphisms and acute leukemia risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets