Faculty of Medicine, Bahri University, Khartoum, Sudan.
Faculty of Medicine, Gadarif University, Gadarif, Sudan.
Mol Genet Genomic Med. 2022 Dec;10(12):e2074. doi: 10.1002/mgg3.2074. Epub 2022 Oct 19.
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.
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.
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.
A significant increase in ESCC risk is associated with the SNPs CDKN1A rs1059234 and MMP9 rs17576.
细胞周期蛋白依赖性激酶抑制剂 (CDKN1A) 基因和基质金属蛋白酶-9 (MMP9) 基因的多态性可能会增加恶性肿瘤的易感性。在这项研究中，研究了苏丹个体中 CDKN1A 基因 rs1059234 c.70C>T 位于 3'非翻译区和 MMP9 rs17576 (c.836A>G, p.Gln279Arg) 的单核苷酸多态性 (SNP) 与食管鳞状细胞癌 (ESCC) 的相关性。
2020 年 4 月至 10 月在苏丹东部加达里夫的癌症中心进行了一项病例对照研究，纳入了年龄和性别匹配的两组人群。病例组为 ESCC 患者，对照组为健康受试者。采用聚合酶链反应-限制性片段长度多态性方法对 CDKN1A rs1059234 和 MMP9 rs17576 进行基因分型。Sanger 测序法对基因分型结果进行了验证。
CDKN1A rs1059234 和 MMP9 rs17576 的基因型分布符合 Hardy-Weinberg 平衡。CDKN1 rs1059234 c.70C>T 的变异等位基因 T 在 ESCC 患者中明显比健康对照组更为常见[51.3% vs. 19.2%；OR=4.4；95%CI（2.6-7.4）；p<0.001]。此外，在 CDKN1A rs1059234 中，TC+TT 基因型[76.9% vs. 38.4%；OR=5.3；95%CI（2.6-10.7）；p<0.001]在病例组中比对照组更为常见，且与 ESCC 风险显著相关。在 MMP9 rs17576 中，变异等位基因 G 在病例组中也明显比对照组更为常见，与病例组 ESCC 风险增加显著相关[27.5% vs. 1.9%；OR=19.4；95%CI（5.8-64.1）；p<0.001]。在病例组中，含有等位基因 G 的两种基因型 (AG+GG) 是最常见的基因型[48.7% vs. 3.8%；OR=23.7；95%CI（6.8-81.7）；p<0.001]，且它们显著增加了 ESCC 的风险。
CDKN1A rs1059234 和 MMP9 rs17576 的 SNP 与 ESCC 风险显著相关。
