Abstract
TGF‐β1 is involved in tumour growth. Four TGFB1 SNPs and TGF‐β1 production by stimulated PBMC were determined in seventy‐eight gastric adenocarcinoma patients. In addition, TGF‐β1 levels were measured in the plasma of further thirty patients. rs1800471‐G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP‐G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP‐T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469‐C/rs1800470‐T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five‐year life expectancy (P = .03). TGF‐β1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF‐β1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF‐β1 levels serves to identify patients at risk of developing a more aggressive disease.
Highlights
Gastric cancer is the fifth most common type of malignancy in the world and the third leading cause of cancer-related deaths worldwide (783 000 deaths in 2018).[1]
One-hundred and eight patients with gastric adenocarcinoma undergoing surgery were involved. This cohort was split as follows: seventy-eight patients were subjected to DNA extraction and subsequent TGFB1 single nucleotide polymorphisms (SNPs) analysis and measurement of TGF-β1 production by purified Peripheral blood mononuclear cell (PBMC), and thirty patients were used to measure plasma TGF-β1 levels
Once the genetic profile of the TGFB1 gene was studied in our group of patients, we decided to test whether the polymorphisms analysed related to the amount of TGF-β1 produced by PBMC upon stimulation with PMA and ionomycin (Figure 3), as described in Materials and Methods
Summary
Gastric cancer is the fifth most common type of malignancy in the world (over one million cases in 2018) and the third leading cause of cancer-related deaths worldwide (783 000 deaths in 2018).[1]. Once the genetic profile of the TGFB1 gene was studied in our group of patients, we decided to test whether the polymorphisms analysed related to the amount of TGF-β1 produced by PBMC upon stimulation with PMA and ionomycin (Figure 3), as described in Materials and Methods.
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