Differential Impact of VNTR Polymorphism in the CBS Gene on Gastric and Breast Cancers Risk

The cystathionine beta-synthase (CBS) gene plays a critical role in numerous physiological processes, including cellular proliferation, bioenergetics, and redox balance, and has been implicated in many cancers, including breast and gastric cancers. Previous studies have suggested that VNTR polymorphism in intron 13 of the CBS gene may influence enzyme activity, as an increase in the number of repeats in this VNTR leads to a reduction in the activity of the CBS enzyme. In this case-control study, for the first time, we genotyped 107 patients with gastric cancer (and 111 healthy controls) and 138 patients with breast cancer (and 124 healthy controls) for the CBS VNTR polymorphism using PCR. Our results showed that individuals with the 18/18 or 19/19 genotypes had a significantly higher risk of developing gastric cancer compared to those with the 17/17 genotype (OR = 2.14, 95% CI 1.12-4.09, p = 0.021). Similarly, the 20/20 or 21/21 genotypes were associated with a significantly increased risk of gastric cancer compared to the 17/17 genotype (OR = 7.93, 95% CI 2.13-29.51, p = 0.002). In contrast, the 18/18 or 19/19 genotypes were found to be significantly associated with a decreased risk of breast cancer compared to the 17/17 genotype (OR = 0.36, 95% CI 0.17-0.75, p = 0.006). In conclusion, our study provides evidence that a higher number of VNTR repeats in intron 13 of the CBS gene is associated with an increased risk of gastric cancer, while a lower number of VNTR repeats is associated with an increased risk of breast cancer.