Oncotarget

Research Papers:

Identification of a synonymous variant in TRIM59 gene for gastric cancer risk in a Chinese population

Dakui Luo _, Younan Wang, Xiangkun Huan, Chi Huang, Chao Yang, Hao Fan, Zekuan Xu and Li Yang

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Oncotarget. 2017; 8:11507-11516. https://doi.org/10.18632/oncotarget.14075

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Abstract

Dakui Luo1,*, Younan Wang1,*, Xiangkun Huan1,*, Chi Huang1,*, Chao Yang2, Hao Fan1, Zekuan Xu1, Li Yang1

1Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

2Liver Transplantation Center of the First Affiliated Hospital and Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu, China

*These authors have contributed equally to this work

Correspondence to:

Li Yang, email: [email protected]

Keywords: gastric cancer, TRIM59, synonymous variant, genotype, Chinese population

Received: July 13, 2016     Accepted: November 22, 2016     Published: December 21, 2016

ABSTRACT

Tripartite motif 59 (TRIM59) is a novel oncogenic driver in gastric cancer (GC) that is implicated in disease progression as well as dismal survival. Genetic variants in peculiar gene are likely candidates for conferring hereditary susceptibility. The role of TRIM59 polymorphism in predicting the risk of malignant diseases and its relevance to TRIM59 expression have not been discussed. Using a HapMap tagSNPs approach, we screened three tag TRIM59 single nucleotide polymorphisms (SNPs) (rs1141023G>A, rs7629A>G, rs11706810T>C) which were genotyped in 602 GC patients and 868 healthy controls. Our study provided convincing result that carries of variant rs1141023A allele markedly increased GC risk (P=0.006). In comparison with the GG homozygotes, the variant GA heterozygotes demonstrated 1.50-fold elevated risk of GC (p=0.014, 95% confidence interval [CI] = 1.09–2.08). Subjects who carried the (GA+AA) genotypes of rs1141023 were associated with remarkable increased GC risk compared with the common genotype (P = 0.013, adjusted OR = 1.50, 95% CI = 1.09–2.05). Further stratified analyses displayed that the relationship between mutant genotype of rs1141023 and GC risk was more profound in male individuals. Intriguingly, there is no significant distinction of TRIM59 mRNA expression between rs1141023GA genotype and GG genotype in 44 normal gastric tissues. Taken together, our results suggest that rs1141023 polymorphism contributes to increased predisposition to GC and thus may be responsible for predicting early GC.


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