The Association of rs5745687 Polymorphism Located at HGF Gene with Risk of Gastric and Breast Cancer in the Helicobacter Positive Patients of Isfahan Population

Hepatocyte growth factor (HGF) protein regulates cell growth, motility, and morphogenesis in a variety of cells and tissues by binding to the HGF receptor. The rs5745687 SNPs in the introns of the HGF gene could affect the splicing and expression of HGF mRNA.

In this study, the genotype frequency of rs5745687 in breast cancer (BC) and gastric cancer (GC) (positive helicobacter) patients has been investigated and compared with the healthy controls in the Isfahan population.

Firstly, initial bioinformatics studies were done. Then, according to the results, bioinformatics High-Resolution Melt (HRM) and Real-Time PCR were recruited to determine genotypes rs5745678 for 432 participants in the case-control analysis (84 GC with 126 healthy control samples, as well as 111 BC cases with 111 normal controls). The conditional logistic regression model was used to measure odds ratios (OR) and 95% confidence intervals (CI) to produce these cancers based on genotype frequency.

The homozygote genotype of the mutant (G) allele of rs5745678 has a significant association with the lower risk of gastric cancer (P-value < 0.0001) and this allele can increase the risk of GC in a co-dominant model (OR: 5.541, P-value < 0.0001). Also, the rs5745678 SNP had a significant association with the clinicopathological features (age, smoking, H. Pylori infection) in GC patients.

The presence of a single G allele in rs5745678 heterozygote (AG/AA) and co-dominant (AG/AA+GG) models could significantly impact GC pathogenicity in different ways. There was no significant correlation between the rs5745678 polymorphism and BC (P-value: 0.671) in the studied sample size.