rs2976392

This case-control study of 1,115 gastric cancer cases and 1,172 Eastern Chinese controls identified six SNPs (rs13361707, rs2294008, rs4072037, rs3762272, rs2274223, rs80142782) associated with increased gastric cancer risk with ORs ranging from 1.19–1.47. A predictive model combining these genetic variants with BMI achieved an AUC of 0.684 compared to 0.653 for BMI alone, and revealed a gene-environment interaction between low BMI and genetic risk variants.

This fine-mapping association study in 1926 European gastric cancer (GC) patients and 2012 controls confirmed associations at chromosome 5p13 (rs6872282, P=2.53×10⁻⁴, OR=1.22) and 8q24 (rs2585176, P=1.09×10⁻⁹, OR=1.34) and characterized them through eQTL analysis. The study found cis-eQTL effects for PTGER4 upregulation (5p13, P=9.27×10⁻¹¹) and PSCA upregulation (8q24, P=2.17×10⁻⁴⁷), plus trans-eQTL effects for MBOAT7 downregulation (8q24, P=1.99×10⁻⁹) in GC risk allele carriers.

Pathway analysis of a gastric cancer GWAS dataset using ICSNPathway identified 7 candidate SNPs (rs4745, rs12904, rs1801019, rs364897, rs11187870, rs2274223, rs3765524) in 4 genes (EFNA1, UMPS, GBA, PLCE1) and 12 biological pathways. Four hypothetical mechanisms were proposed: ephrin receptor binding via EFNA1, pyrimidine metabolism via UMPS, cyanoamino acid metabolism via GBA, and cell growth/lipid biosynthesis via PLCE1.

Case-control study of PSCA rs2294008 C/T polymorphism in 107 South Indian urothelial bladder cancer patients and 105 controls. The CT heterozygous genotype conferred 2.77-fold increased risk (p<0.0001), and the T allele showed 3.35-fold risk (OR=3.349, p<0.0001). Risk was significantly elevated in smokers (OR CT/TT=2.374) and inversive tumors (OR CT/TT=2.658), suggesting rs2294008 as a susceptibility marker for bladder carcinogenesis.

A meta-analysis of 9 case-control studies (10,746 cases, 9,158 controls) found that PSCA rs2294008 C>T and rs2976392 G>A polymorphisms are significantly associated with increased gastric cancer risk, with ORs of 1.61 (95% CI 1.35-1.91) and 1.69 (95% CI 1.24-2.31) respectively. The association was particularly strong for non-cardia and diffuse-type gastric cancer subtypes in both Asian and European populations.

Case-control study of 692 stomach cancer cases and 774 controls in a Chinese population found significant associations between four GWAS-identified SNPs and gastric cancer susceptibility: PSCA rs2294008 (OR=1.37, 95% CI=1.07-1.74), PSCA rs2976392 (OR=1.30, 95% CI=1.02-1.65), and PLCE1 rs2274223 (OR=1.48, 95% CI=1.15-1.90) increased risk, while MUC1 rs4072037 (OR=0.77, 95% CI=0.60-0.98) was protective. Subjects carrying 2-4 risk genotypes had significantly increased stomach cancer risk (OR=1.30, 95% CI=1.03-1.64).

A case-control study of 692 stomach cancer cases and 774 controls in a Han Chinese population examined associations of four GWAS-identified SNPs with gastric cancer susceptibility. PSCA rs2294008 (CT: OR=1.37, 95% CI=1.07-1.74), PSCA rs2976392 (AG: OR=1.30, 95% CI=1.02-1.65), and PLCE1 rs2274223 (AG: OR=1.48, 95% CI=1.15-1.90) were all significantly associated with increased stomach cancer risk, while MUC1 rs4072037 (CT: OR=0.77, 95% CI=0.60-0.98) was protective. Carriers of multiple risk genotypes had significantly elevated cancer risk.

Letter to the editor discussing peritoneal carcinomatosis from gastric cancer management and genetic susceptibility. Authors discuss GWAS findings including PSCA variants rs2976392 and rs2294008 at 8q24 associated with diffuse-type gastric cancer in Asian populations, and SNPs at 1q22 (rs4072037) and 10q23 (rs2274223) associated with gastric cancer risk in Chinese populations. The letter emphasizes the need for prospective randomized trials and future GWAS studies to identify novel genetic loci for peritoneal metastasis susceptibility.

Case-control study of 692 stomach cancer cases and 774 controls in Han Chinese examining associations between four GWAS-identified SNPs and gastric cancer risk. PSCA rs2294008 (OR=1.37), rs2976392 (OR=1.30), and PLCE1 rs2274223 (OR=1.48) showed increased risk, while MUC1 rs4072037 was protective (OR=0.77). Combined risk genotypes increased cancer susceptibility.

Case-control study of 1020 NCGC patients, 716 CGC patients, and 1020 controls in Chinese population examined associations of two PSCA SNPs with gastric cancer risk. rs2294008T allele was associated with increased noncardia gastric carcinoma (NCGC) risk (OR=1.35, 95% CI=1.13-1.61), and rs2976392A allele showed borderline increased risk (OR=1.20, 95% CI=1.01-1.43). The increased risk was restricted to female subjects, and both SNPs were associated with poorly differentiated and high-stage NCGC at diagnosis. No associations were detected for cardia gastric carcinoma (CGC).

Case-control study (692 cases, 774 controls) in Han Chinese population examining associations of four GWAS-identified SNPs with stomach cancer risk. PSCA rs2294008 (CT vs CC: OR=1.37, 95% CI=1.07-1.74), PSCA rs2976392 (AG vs GG: OR=1.30, 95% CI=1.02-1.65), and PLCE1 rs2274223 (AG vs AA: OR=1.48, 95% CI=1.15-1.90) were associated with increased stomach cancer risk, while MUC1 rs4072037 (CT vs TT: OR=0.77, 95% CI=0.60-0.98) was protective.