P-0027 Genetic Analysis of 5A/6A Promotor Polymorphism of MMP-3 Gene in Gastric Cancer

ABSTRACT Introduction Gastric cancer is a multifactorial disease which is ranked as second degree as the cause of death due to cancer in the world. Diet type, environmental factors, cigarette, excessive alcohol consumption and Helicobacter pylori (H. pylori) infection are the main risk factors of the gastric cancer. During gastric carcinogenesis, basal membranes of the tumor cells are disrupted by matrix metalloproteinase (MMP) enzyme family in an uncontrolled manner. Matrix metalloproteinases are zinc-dependent enzymes and MMP-3 has the largest substrate range in this family. 5A/6A polymorphism of MMP-3 promoter has been studied especially in lung, ovary, breast, and colon cancers and has been accepted as a risk factor. In this study we aimed to analyze the insertion deletion 5A/6A polymorphism at the -1171 position of MMP-3 gene in the tumor and normal tissues obtained from gastric cancer patients and then compare the genotype groups with the expression patterns of MMP-3 gene, and the pathological data of the patients. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping of 41 tumor and normal tissue obtained from gastric cancer patients. The RNA expression levels of MMP-3 gene were determined by reverse transcription- polymerase chain reaction (RT-PCR). Observed genotype groups are compared according to H. pylori infection, RNA expression, invasion depth, and tumor grade and tumor necrosis. Results Normal and tumor tissues of patients displayed the same genotype. 22 of 41 tumor tissues showed 5A/6A genotype with a frequency of 0.537, while 19 out of 41 tissues displayed 6A/6A genotype with a frequency of 0.463. There was no 5A/5A polymorphism among the tested samples. There was a significant difference among the genotype groups when RNA expressions were compared (p=0.035) and there was a cut-off level of significance when the genotypes were compared according to the invasion depth (p=0.064). On the other hand, no association between the genotype groups and tumor necrosis, H. pylori infection, and tumor stage was observed. Conclusion Our data reveals that -1171 MMP-3 5A/6A polymorphism might play an important role in the regulation of expression of MMP-3 gene at the transcriptional level and association of invasion in gastric cancers and consequently might be a biomarker in gastric cancers.