The functional variant in promoter of OVCA1 was associated with the risk of gastric cancer in the northeast Chinese Han population

We previously found allelic deletions on chromosomes 17 in primary gastric cancers (GC) using microsatellite markers for loss of hetemzygosity (LOH). OVCA1 lies in one of these regions (17q21.33). The association between single nucleotide polymorphism (SNP) of OVCA1 gene and risk of gastric cancer is not yet clear. In this study, the peripheral blood of 505 gastric cancer patients and 544 healthy controls were genotyped for six SNPs (rs2273981, rs1131600, rs3752963, rs3803806, rs2236375, and rs1051322) of OVCA1, to evaluate the association of these SNPs with the risk of gastric cancer in the Han population in northeast China. The effect of rs2273981 located in the promoter region of OVCA1 on the transcription activity was determined using dual luciferase reporter assay. We found that the association between the AA + AG genotype of rs2273981 and the risk of gastric cancer was significant in smokers (AA + AG vs. GG, OR = 2.47, 95% CI = 1.04 - 5.87, P < 0.05). Stratified analysis of the clinicopathological parameters revealed that rs1131600 AG + GG genotype were significantly associated with increased gastric tumor volume (AG + GG vs. AA, OR = 1.81, 95% CI = 1.00 - 3.29, P < 0.05). The rs2236375 CT + TT genotype was also significantly associated with increased gastric tumor volume (CT + TT vs. CC, OR = 2.65, 95% CI = 1.38 - 5.10, P < 0.05). Additionally, by interacting with the transcription factor AP2A, the GG genotype the rs2273981 increased the transcription activity of OVCA1 compared with AA genotype, thus involved in gastric cancer development.

Automated summary

In this study, the association between six single nucleotide polymorphisms (SNPs) of the OVCA1 gene and the risk of gastric cancer in the Han population of northeast China was evaluated. The study found that the AA + AG genotype of rs2273981 was significantly associated with an increased risk of gastric cancer in smokers, while the AG + GG genotype of rs1131600 and the CT + TT genotype of rs2236375 were significantly associated with increased gastric tumor volume. Furthermore, the rs2273981 GG genotype increased the transcription activity of OVCA1, potentially contributing to gastric cancer development.