Evaluation of genetic variants in nucleosome remodeling and deacetylase (NuRD) complex subunits encoding genes and gastric cancer susceptibility.

ABSTRACT

Epigenetic complex NuRD (nucleosome remodeling and deacetylase) engages in a range of basic cellular processes, including chromatin modification. Changes in the activity of NuRD complex can influence gastric cancer progression. Multivariate logistic regression analyses were used to estimate the association between single-nucleotide polymorphisms (SNPs) and gastric cancer risk. Expression quantitative trait loci (eQTL) analysis was used to analyze the relationship between the genotypes and gene expression levels using data from the genotype tissue expression project (GTEx). Gene expression was calculated using databases from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO). Kaplan-Meier plotter was used to evaluate the association between gene expression and survival. SNP rs11064275 T allele in CHD4, rs892022 A allele and rs2033481 A allele in GATAD2A were found to contribute to the decreased risk of gastric cancer. The increase in the number of favorable alleles of these three SNPs was associated with a lower risk of gastric cancer. rs2033481 and rs892022 were substantially correlated with GATAD2A mRNA expression levels. Meanwhile, we detected that the CHD4 and GATAD2A mRNA expression was increased in gastric cancer tissues compared with the adjacent normal tissues. Furthermore, we found that patients with higher CHD4 or GATAD2A mRNA expression level had more advantageous overall survival. Our findings indicated that genetic variants in NuRD complex subunits encoding genes may be promising predictors of gastric cancer risk.