PSCA and MUC1 Gene Polymorphisms Are Linked with Gastric Cancer and Pre-malignant Gastric Conditions (original) (raw)

2014, Anticancer Research

Background/Aim: Genome-wide association studies revealed a link between gastric cancer (GC) and single nucleotide polymorphisms (SNPs) of prostate stem cell antigen (PSCA), phospholipase C epsilon-1 (PLCE1) and mucin-1 (MUC1) genes. Herein, we aimed to evaluate associations between PSCA (C>T, rs2294008; G>A, rs2976392), MUC1 (C>T, rs4072037) and PLCE1 (A>G, rs2274223) SNPs and GC or high-risk gastritis (HRAG). Materials and Methods: Using TaqMan system, SNPs were genotyped in 252 patients with GC, 136 patients with HRAG and 246 controls. Results: PSCA rs2294008 allele T was linked with risk of GC (odds ratio (OR)=1.88, p<0.001) and HRAG (OR=1.49, p=0.009). Allele A of PSCA rs2976392 was associated with development of GC (OR=1.88, p<0.001) and HRAG (OR=1.56, p<0.01). MUC1 rs4072037 allele G was protective against development of GC (OR=0.64, p=0.0005), while no differences were found for PLCE1 rs2274223. Conclusion: Polymorphisms of PSCA (rs2976392, rs2294008) and MUC1 (rs4072037) genes are linked with GC and HRAG. Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide (1). Most recent reports on cancer reveal a declining incidence of GC in Western countries; nevertheless, the mortality associated with GC remains very high (1). The pathways of GC pathogenesis have merged into a complex picture, which involves Helicobacter pylori infection as well as genetic, epigenetic and other co-founding factors (2). A genome-wide association study (GWAS) approach has been applied in various diseases including cancer. The first GWAS on GC was published in 2008 and identified an association with a single nucleotide polymorphism (SNP) of prostate stem cell antigen (PSCA) gene (3). A few GWAS studies confirmed this association and revealed new susceptibility loci at mucin-1 (MUC1) and phospholipase C epsilon-1 (PLCE1) genes (3, 4). Gene SNPs detected in the aforementioned GWAS studies have been implicated in various cancer-related molecular pathways. PSCA gene encodes a cell membrane glycoprotein responsible for cellular activation (3). PSCA gene is expressed in the epithelium of the stomach and it is particularly down-regulated in gastric tissue with intestinal metaplasia (3). MUC1 gene encodes a cell membrane protein that plays a role in forming protective mucous barriers on stomach epithelial surfaces and is essential in intracellular signaling (5). Different studies have shown that MUC1 is involved in the regulation of H. pylori-induced chronic gastritis (5). PLCE1 gene encodes an enzyme that catalyzes hydrolysis which generates second messengers affecting the cell cycle (6). The PLCE1-related signaling network has an impact on several critical carcinogenetic processes, including proliferation, cell survival, metabolism, and tumor growth (6). The changes of encoding sequences of these genes have functional roles and may influence the process of carcinogenesis.