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PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

ABSTRACT: The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population. We found that the rs2294008T variant genotypes were associated with an increased GCa risk in this study population (CT vs CC, OR=1.59, 95% CI=1.33-1.89 and CT+TT vs CC, OR=1.38, 95% CI=1.17-1.62). For SNP rs2976392, the variant A genotypes were also associated with an increased GCa risk (AG vs GG, OR=1.61, 95% CI=1.35-1.91 and AG+AA vs GG, OR=1.47, 95% CI=1.25-1.74). The results were further validated by a meta-analysis. In conclusion, the results indicated that the PSCA rs2294008 T and rs2976392 A alleles were low-penetrate risk factors for GCa in this study population. However, large and well-designed studies are warranted to validate our findings.

SUBMITTER: Qiu LX

PROVIDER: S-EPMC4891049 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

Qiu Li-Xin LX Cheng Lei L He Jing J Zhou Zhi-Rui ZR Wang Meng-Yun MY Zhou Fei F Guo Wei-Jian WJ Li Jin J Sun Meng-Hong MH Zhou Xiao-Yan XY Wang Ya-Nong YN Yang Ya-Jun YJ Wang Jiu-Cun JC Jin Li L Zhu Xiao-Dong XD Wei Qing-Yi QY

Oncotarget 20160201 8

The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population. We found that t ...[more]

PMID: 26848528

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Project description:IntroductionGenetic factors play an important role in the development of gastric cancer (GC), a prevalent malignancy in Central Asia. Recent studies have shown that single-nucleotide polymorphisms (SNPs) in several genes are associated with increased GC risk, indicating that genetic variation contributes to gastric carcinogenesis. Located on chromosome 8q24.2, the prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein related to the cell-proliferation inhibition and cell-death induction activity. SNPs in PSCA gene have been found to be associated with gastric cancer risk in a genome-wide association study, but results were not conclusive. This study aimed to investigate the association between two polymorphic variants of PSCA gene (rs2294008 and rs9297976) and the susceptibility to gastric cancer in Uzbekistan.MethodsTwo hundred sixty eight patients with gastric cancer and a control group of 248 healthy individuals were included in this study. DNA samples isolated from these groups were genotyped using PCR-RFLP method. Comparative analysis of resulting genotypes showed a statistically significant association between CT genotype and gastric cancer (p=0.03, additive model of inheritance, Cochran-Armitage trend test).ResultsComparative analysis of the distribution of genotypes of rs2976392 polymorphism did not show a statistically significant difference; however, analysis of the distribution of the rs2976392 genotypes in a subgroup of young women revealed a statistically significant (p = 0.04, additive model of inheritance, Cochran-Armitage trend test) increase in the incidence of AA (38%) and AG (56%) genotypes in patients with GC, compared to the controls (20% and 40%).ConclusionOur findings support that PSCA rs2294008 and rs9297976 polymorphism may contribute to the susceptibility to gastric cancer. Genotyping of these polymorphisms can potentially be recommended as one of the criteria for identification of high risk groups for gastric cancer development in Uzbekistan.

Project description:PurposePrevious studies showed that peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPARγ, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC).Patients and methodsWe performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPARγ rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscantm Kit.ResultsThe PPARγ rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42-0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42-0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPARγ rs1801282 SNV was correlated with the risk of GC in subgroups of age ≥ 61, no smoking, and no alcohol consuming. We also confirmed that the PPARγ rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI ≥ 24 kg/m2. The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI ≥ 24 kg/m2.ConclusionThis study indicates that the PPARγ, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.

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PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

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PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

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