Association of COL4A2 indel polymorphism with the development of stomach adenocarcinoma in Chinese populations

The objective of the study was to assess the potential association between the indel polymorphism (rs34802628) located within the intron of the collagen type ⅳ alpha 2 gene (<i>COL4A2</i>) and the susceptibility to stomach adenocarcinoma (STAD) within a Chinese population. Peripheral venous blood samples were collected from a total of 497 STAD patients and 804 healthy control individuals to extract genomic DNA. The genotyping of the <i>COL4A2</i> rs34802628 polymorphism was carried out using a polymerase chain reaction assay. Additionally, statistical analyses were conducted on the expression levels of COL4A2 mRNA using the GEPIA database. Meanwhile, the expression of COL4A2 mRNA was also validated by Real-time PCR using STAD tissue samples. Then, based on an analysis of patient tumor RNA seq data available from the Cancer Genome Atlas (TCGA), we assessed the prognostic value of mRNA expression of the <i>COL4A2</i> gene in STAD patients using K–M plotter. The study presented compelling evidence supporting an association between the rs34802628 polymorphism in the <i>COL4A2</i> gene and susceptibility to STAD. Logistic regression analysis revealed that both the heterozygote and homozygote 4-bp del/del genotypes were significantly associated with a decreased risk of STAD, even after controlling for other variables (adjusted odds ratio [OR] = 0.663, 95% confidence interval [CI] 0.519–0.848, <i>p</i> = 0.037; OR = 0.422, 95% CI 0.290–0.614, <i>p</i> = 0.000005, respectively). Importantly, individuals carrying the 4-bp deletion allele demonstrated a notably lower risk of developing the disease (OR = 0.696, 95% CI 0.591–0.820, <i>p</i> = 0.000014). Furthermore, Genotype-phenotype correlation studies in human STAD tissue samples demonstrated that the higher mRNA expression levels of COL4A2 were associated with the ins allele of rs34802628. Bioinformatics analysis revealed that higher expression of the <i>COL4A2</i> gene was significant with development and poor prognosis of STAD. The results of our study provide strong evidence indicating a potential involvement of genetic variants in the <i>COL4A2</i> gene in the development of STAD. Nonetheless, to validate and consolidate these findings, additional investigations incorporating larger sample sizes and functional experiments are necessary.