Upstream stimulating factor 1 (USF1) -202 G/A polymorphism and serum levels of USF1 and USF2 are associated with gastric cancer risk: a case control study

Abstract

Abstract Purpose Gastric cancer is an inflammation-driven disease often associated with a bad prognosis. Upstream stimulatory factors USF1 and USF2 are pleiotropic transcription factors, with tumor suppressor function. Low expression of USF1 is associated with low survival in gastric cancer patients. USF1 genetic polymorphism -202G > A has been associated with cancer susceptibility. Our aim was to investigate USF1 gene polymorphism and serum level with the risk of gastric cancer. Methods USF1-202 G/A polymorphism was analyzed by sanger sequencing, with the measure of USF1/USF2 serum levels by ELISA in H. pylori-positive patients with chronic gastritis, gastric precancerous lesions, gastric cancer and in healthy controls. Results Our results show that the presence of the USF1-202 A allele increased the risk of gastric cancer compared to G (OR = 2; 95% CI 1.07–3.9; P = 0.02). Genotypically and under the dominant mutation model, the combined USF1- GA/AA -202 genotypes corresponded to higher risk of gastric cancer (OR = 3.5; 95% CI 1.4–8.2; p-value = 0.005) than the GG genotype. Moreover, the G/A transition at USF1-202 was associated with lower USF1 serum level, and mostly observed in gastric cancer patients where the average serological level of USF1 were 2.3 and twofold lower for the AA and GA genotypes, respectively, compared to GG. Conclusion USF1-202 G/A polymorphism constitutes a gastric cancer genetic risk factor. Together with USF1/USF2 serum level, they can be proposed as promising biomarkers for gastric cancer detection/prevention.

Keywords

• Gastric cancer
• Genetic polymorphism
• Genetic risk factor
• Biomarkers
• Serum