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

// Jingdong Wang 1, * , Chade Li 1, * , Fengting Wan 1 , Zhou Li 1 , Jingli Zhang 1 , Jiankun Zhang 1 , Xianhong Feng 2 , Liang Tang 3 , Bifeng Chen 1 1 Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China 2 Clinical Laboratory, Wuhan Xinzhou District People's Hospital, Wuhan, China 3 Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, China * These authors contributed equally to this work Correspondence to: Bifeng Chen, email: cbifeng@whut.edu.cn Liang Tang, email: tlcool318@163.com Keywords: non-small cell lung cancer, DNMT3A, rs1550117, Han Chinese population Received: September 20, 2016      Accepted: February 14, 2017      Published: February 22, 2017 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.