Gene polymorphisms of cyclin-dependent kinase inhibitor and matrix metalloproteinase-9 in Sudanese patients with esophageal squamous cell carcinoma.

BACKGROUND

The polymorphisms of the cyclin-dependent kinase inhibitor (CDKN1A) gene and matrix metalloproteinase-9 (MMP9) gene may increase one's susceptibility to malignancies. In this study, the association of the single nucleotide polymorphisms (SNPs) CDKN1A rs1059234 c.70C>T at the 3' untranslated region and MMP9 rs17576 (c.836A>G, p.Gln279Arg) with esophageal squamous cell carcinoma (ESCC) in Sudanese individuals were investigated.

MATERIALS AND METHODS

A case-control study involving age- and gender-matched groups were conducted in a cancer center in eastern Sudan (Gadarif) between April and October 2020. The case group consisted of ESCC patients, whereas the control group comprised healthy subjects. Polymerase chain reaction-restriction fragment length polymorphism was performed for the genotyping of the CDKN1A rs1059234 and MMP9 rs17576 SNPs. The genotyping results were confirmed by Sanger sequencing.

RESULTS

The genotype distributions for CDKN1A rs1059234 and MMP9 rs17576 were in agreement with the Hardy-Weinberg equilibrium. The variant allele T in CDKN1 rs1059234 c.70C>T was significantly more prevalent in the ESCC patients than in the healthy controls [51.3% vs. 19.2%; OR = 4.4; 95% CI (2.6-7.4); p < 0.001]. Moreover, in CDKN1A rs1059234, the genotype TC + TT [76.9% vs. 38.4%; OR = 5.3; 95% CI (2.6-10.7); p < 0.001] was more frequent in the cases than in the controls, and it was significantly associated with ESCC risk. In MMP9 rs17576, the variant allele G was also significantly prevalent in the cases relative to the controls, and it was significantly associated with increased ESCC risk in the cases compared with the controls [27.5% vs. 1.9%; OR = 19.4; 95%CI (5.8-64.1); p < 0.001]. Both genotypes containing the allele G (AG + GG) were the most common genotypes in the cases [48.7% vs. 3.8%; OR = 23.7; 95%CI (6.8-81.7); p < 0.001], and they significantly increased the risk of ESCC.

CONCLUSION

A significant increase in ESCC risk is associated with the SNPs CDKN1A rs1059234 and MMP9 rs17576.