The rs1550117 A>G variant in DNMT3A gene promoter significantly increases non-small cell lung cancer susceptibility in a Han Chinese population

Abstract

In this study, we conducted a case-control study to explore the association between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of rs1550117 A>G variant was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA genotype carriers. Further stratified analysis showed that rs1550117 A>G was significantly related to age (> 60 years), male, smoking and drinking. In vivo detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays consistently showed that the allele G significantly decreased DNMT3A transcription. Additional functional analysis revealed that the increased binding affinity of transcription repressor SP1, which was associated with allele G of rs1550117, led to the significant decreased expression of DNMT3A. Collectively, our results propose a suppression role of DNMT3A in NSCLC development and emphasize the dual roles of DNMT3A in tumorigenesis.

A meta-analysis on the susceptibility to the development of bladder cancer in the presence of DNMT3A, DNMT3B, and MTHFR gene polymorphisms

“…There was no association between these two polymorphisms with the risk of bladder carcinogenesis. This result is in contrast to what has been reported on the DNMT3A rs1550117 variant, which showed a significantly increased risk of developing non-small cell lung cancer (NSCLC) in the Han Chinese population [55]. While Wang et al found that the rs1550117 AG/AA genotype was significantly associated with an increased mortality rate compared with individuals carrying the GG genotype, suggesting that DNMT3a rs1550117 may be a relevant prognostic element for gastric cancer [56].…”

Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non–small-cell lung cancer

“…In contrast to the widely reported high-frequency mutated genes mentioned above, CREBBP (23.1%), KMT2C (16.9%), MUC2 (16.6%), DNMT3A (15.5%), LRP1B (15.5%), MUC4 (15.5%), and CDC27 (15.2%) are currently reported less in the Chinese population, although mutations in DNMT3A and KMT2C have been identified in some studies [ 20 , 33–35 ]. Our results suggest some aspects of the mutational characteristics of these genes in Chinese NSCLC, suggesting functions of these genes in the etiology and treatment of NSCLC.…”

“…In some reports, it is described that the frequency of conversion of KRAS in the Chinese is approximately 8% [ 25 , 32 ]. Here, we report a mutation rate of the KRAS gene of 12.8% [ 33 ].…”

Aberrations of DNA methylation in cancer

“…Однако в другом исследовании было показано, что у женщин из популяции Хань, проживающих на юге Китая, генотип DNMT1-290 CT (rs16999593) ассоциирован с повышенным риском развития рака молочной железы [55]. Также для китайской популяции Хань было выявлено, что генотип DNMT3a-786 GG (rs1550117) ассоциирован с предрасположенностью к немелкоклеточному раку легкого [56].…”