Association between the SNPs of the TOB1 gene and gastric cancer risk in the Chinese Han population of northeast China

Abstract

The TOB1 (ErbB-2,1) gene is an anti-proliferative factor that has the potential to regulate cell growth and encodes a member of the transducer of erbB-2/B-cell translocation gene protein. The association between the polymorphisms of the TOB1 gene and gastric cancer (GC) risk is still unclear. In this study, 506 GC cases and 548 healthy controls (HCs) were collected to evaluate the association between the eleven SNPs (rs35220381, rs12950561, rs7221352, rs61482741, rs9303568, rs34700818, rs12949115, rs9903822, rs12601477, rs11656976 and rs4626) of the TOB1 gene and GC risk in the population of northeast China. The results showed that there were significant associations of haplotype GCCTTGC, haplotype ATCTTGG, and haplotype GCCACGC with GC risk (P < 0.05, P < 0.001, and P <0.001, respectively). The association between rs12601477 GA+AA genotypes and GC risk was significant among individuals older than 58 (adjusted OR=1.53, 95% CI=1.05-2.22, P< 0.05). The association between rs4626 AG+GG genotypes and GC risk was significant among individuals older than 58 (adjusted OR=1.54, 95% CI = 1.03-2.28, P<0.05). The rs34700818 CT+TT genotypes were associated with a significantly increased risk of T3-T4 (CT+TT vs CC, adjusted OR=1.71, 95% CI= 1.01-2.88, P<0.05) and TNM stage II (CT+TT vs CC, adjusted OR=2.40, 95% CI =1.27-4.52, P<0.01). The rs61482741 CG+GG genotypes were also associated with a significantly increased risk of T3-T4 (CG+GG vs CC, adjusted OR=1.71, 95% CI = 1.01-2.88, P<0.05) and TNM stage II (CG+GG vs CC, adjusted OR=2.40, 95% CI=1.27-4.52, P<0.01). The results suggest that four SNPs (rs12601477, rs4626, rs34700818 and rs61482741) of the TOB1 gene play an important role in the occurrence and development of GC in the Chinese Han population of northeast China.

Involvement of TOB1 on autophagy in gastric cancer AGS cells via decreasing the activation of AKT/mTOR signaling pathway

“…Both effects involve complex regulatory networks, such as those mediated by p53, PI3K/AKT/mTOR, Ras, and microRNA ( Zhou et al, 2016 ). Our group has demonstrated that TOB1 is a tumor suppressor in gastric cancer ( Guan et al, 2017 ; Guo et al, 2019 ; Wang et al, 2019 ; Wang et al, 2018 ; Yu et al, 2011 ; Yu et al, 2008a ; Yu et al, 2008b ). Experimental data from our study indicated that TOB1 may induce autophagy in gastric cancer cells.…”

The rs9953490 polymorphism of DAL-1 gene is associated with gastric cancer risk in the Han population in Northeast China

“…The candidate SNPs were selected using the dbSNP database ( http://www.ncbi.nlm.nih.gov/snp ) and the 1000 Genomes database ( https://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/ ). These SNPs were selected based on the criterion of the minor allele frequency (MAF) greater than 0.05 in the Chinese Han population [ 21 ]. Ultimately, six SNPs (rs7240736, rs73937194, rs3817466, rs8082898, rs73381527 and rs9953490) of DAL-1 gene met the requirement and were included in our study in Table 1 .…”

“…Continuous variables with a normal distribution were described as mean ± SD and compared with the Student’s t-test [ 21 ]. Discrete variables we re described as frequency (percentage) and compared using the Chi-square (χ 2 ) test [ 21 ].…”

“…Continuous variables with a normal distribution were described as mean ± SD and compared with the Student’s t-test [ 21 ]. Discrete variables we re described as frequency (percentage) and compared using the Chi-square (χ 2 ) test [ 21 ]. Genotype frequencies for each polymorphism in the control group were tested by Hardy–Weinberg equilibrium using the χ 2 test.…”

“…Xu et al [ 20 ] found that SNP rs4880 of SOD2 gene and SNP rs1695 of GSTP1 gene may increase cancer progression and tumor aggressiveness. Recently, we found that two SNPs (rs34700818 and rs61482741) of TOB1 gene were significant associated with increased GC progression [ 21 ]. Therefore, we investigated the association between six SNPs of DAL-1 gene and GC risk in a cohort of 505 GC patients and 544 healthy controls (HCs).…”