The Importance of STAT3 Genetic Variation in Gastric Cancer Susceptibility

Gastric cancer is the second most common cause of cancer related deaths, and nearly 1 million new cases are diagnosed worldwide each year. STAT3 is a key transcription factor for many cytokines and growth factors and plays a critical role in maintaining intracellular homeostasisin many aspects involving the regulation of cell proliferation, apoptosis, angiogenesis, metastasis, malignant transformation, immune evasion and invasion, all of which are hallmarks of cancer. An obvious association between STAT3 gene polymorphisms and risk of cancers has been confirmed in different studies.
Given the prevalence of gastric cancer in Iran and the central role of STAT3 in different cancers including gastric cancer, the aim of this study was to investigate the association between STAT3 gene polymorphism (rs1053023) and gastric cancer.
This case-control study comprised of two groups: 120 patients and 150 healthy controls from Guilan province. After genomic DNA extraction from leukocytes, genotyping was carried out by tetra primers amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). MedCalc software (version 12.2) was applied for statistical analysis.
Among the cases, the proportions of STAT3 (rs1053023) AA, AG and GG were 75%, 19% and 6%, respectively. In the controls; these proportions were 22%, 60% and 18%. Allele frequencies of the STAT3 gene A and G were 84.5% and 15.5% in patients, while in the controls were 52% and 48%, respectively. Significant differences were found between cases and controls in Allele and genotype distributions of the STAT3 rs1053023 (p= 0.0007 and p=0.0001, respectively). The risk for gastric cancer associated with the A allele increased by five-folds [95% confidence interval (CI): 3.33-7.68]. Carriers of the AA genotype exhibited 10.5-fold (95% CI: 4.18-26.45) increased risk of gastric cancer, compared with the carriers of AG and GG genotype.
In conclusion, the results of the present study indicate that STAT3 rs1053023 polymorphism is associated with the risk of gastric cancer in Guilan province. However, further research is required to clarify the role of STAT3 polymorphism in gastric cancer.