Abstract

BackgroundGastric cancer is one of the four most common cancer that causing death worldwide. Genome-Wide Association Studies (GWAS) have shown that genetic diversities MUC1 (Mucin 1) and PSCA (Prostate Stem Cell Antigen) genes are involved in gastric cancer. The aim of this study was avaluating the association of rs4072037G > A polymorphism in MUC1 and rs2294008 C > T in PSCA gene with risk of gastric cancer in northern Iran.MethodsDNA was extracted from 99 formalin fixed paraffin-embedded (FFPE) tissue samples of gastric cancer and 96 peripheral blood samples from healthy individuals (sex matched) as controls. Two desired polymorphisms, 5640G > A and 5057C > T for MUC1 and PSCA genes were genotyped using PCR-RFLP method.ResultsThe G allele at rs4072037 of MUC1 gene was associated with a significant decreased gastric cancer risk (OR = 0.507, 95% CI: 0.322–0.799, p = 0.003). A significant decreased risk of gastric cancer was observed in people with either AG vs. AA, AG + AA vs. GG and AA+GG vs. AG genotypes of MUC1 polymorphism (OR = 4.296, 95% CI: 1.190–15.517, p = 0.026), (OR = 3.726, 95% CI: 2.033–6.830, p = 0.0001) and (OR = 0.223, 95% CI: 0.120–0.413, p = 0.0001) respectively. Finally, there was no significant association between the PSCA 5057C > T polymorphism and risk of gastric cancer in all genetic models.ConclusionResults indicated that the MUC1 5640G > A polymorphism may have protective effect for gastric cancer in the Northern Iran population and could be considered as a potential molecular marker in gastric cancer.

Highlights

  • Gastric cancer is one of the four most common cancer that causing death worldwide

  • Mucin 1 (MUC1) rs4072037 polymorphism is associated with significant decreased gastric cancer risk in four genetic models: G vs. A (OR = 0.507, 95% confidence interval (CI): 0.322–0.799, p = 0.003); heterozygous AG compared with AA (OR = 4.296, 95% CI: 1.190–15.517, p = 0.026); dominant model AG + AA vs. GG (OR = 3.726, 95% CI: 2.033–6.830, p = 0.0001); and over-dominant model AA+GG vs. G (OR = 0.223, 95% CI: 0.120–0.413, p = 0.0001) (Table 4)

  • No significant association was observed between the Prostate Stem Cell Antigen (PSCA) 5057C > T polymorphism and risk of gastric cancer in all genetic models (T vs. C (OR = 1.050, 95% CI: 0.652–1.693, p = 0.840); homozygous TT vs. CC (OR = 0.903, 95% CI: 0.327–2.492, p = 0.533); heterozygous CT vs. CC (OR = 1.228, 95% CI: 0.644–2.339, p = 0.533); dominant model CT + CC vs. TT (OR = 1.137, 95% CI: 0.420–3.080, p = 0.800); and recessive model CC vs. CT + TT (OR = 0.904, 95% CI: 0.505–1.620, p = 0.735))

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Summary

Introduction

Gastric cancer is one of the four most common cancer that causing death worldwide. Genome-Wide Association Studies (GWAS) have shown that genetic diversities MUC1 (Mucin 1) and PSCA (Prostate Stem Cell Antigen) genes are involved in gastric cancer. The aim of this study was avaluating the association of rs4072037G > A polymorphism in MUC1 and rs2294008 C > T in PSCA gene with risk of gastric cancer in northern Iran. Gastric cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death [1]. Northern and northwestern regions of Iran are at high risk for gastric cancer [2]. The mortality rate from stomach cancer is the first cause of death due to cancer in both sexes in Iran [5, 6]. From 2000 to 2005, the incidence rate was highest in northern

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