Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin’s lymphoma in Egyptians

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of extracellular matrix degradation. MMP2 is the key molecule that control invasion, tumor growth, and metastasis, and has been associated with poor prognosis in several tumors. Several epidemiological studies have focused on the associations between MMP2 promoter polymorphisms and cancer susceptibility; however, little is known about their role in hematological malignancies. The present study aimed to investigate the association of MMP2 -735C/T and -1306C/T promoter polymorphisms with B-NHL susceptibility and their clinicopathological characteristics. The study included 100 B-NHL patients and 100 healthy controls. Genotyping of MMP2 -735C/T and MMP2 -1306C/T was done by polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique. MMP2 -735C/T heteromutant genotype (CT) was detected in 23 % of patients, and the homomutant genotype (TT) was detected in 7 % of patients. The polymorphic allele, T allele, was associated with susceptibility to B-NHL (OR = 2.8:95 %CI = 1.48-5.28). For MMP2 -1306C/T, the frequencies of the polymorphic variants were 5 % for the heteromutant genotype (CT) and 3 % for the homomutant genotype (TT). The polymorphic allele, T allele, conferred almost fourfold increased risk of B-NHL (OR = 3.8, 95 %CI = 1.05-13.9), and the risk elevated to be almost eight folds when confined to diffuse large B-cell lymphoma (DLBCL) (OR = 7.9, 95 %CI = 1.67-32.27). MMP2 -735C/T polymorphic genotypes were correlated with advanced clinical stages of the disease (stages III and IV). In conclusion, the study revealed that the variant alleles of MMP2 -735C/T and MMP2 -1306C/T can be considered as molecular risk factors for B-NHL among Egyptians.

Matrix Metalloproteinase-2 Single Nucleotide Polymorphism in Egyptian Non-Hodgkin Lymphoma Patients: Correlation with Clinicopathological Characteristics and Outcome

“…Here in our NHL patients, 80% of patients were homozygous wild genotype (CC), 14% of them were heterozygous genotype (CT), while 6% had the homozygous mutated genotype (TT). These results are close to what reported by Gouda et al [22] who found that 23% of cases had the heterozygous genotype (CT), while 7% had the homozygous mutated genotype (TT). In another study of Diao et al on Chinese, it was reported that 30% were heterozygous, and 5.9% were homozygous mutated.…”

“…TT genotypes and treatment response including complete or partial remission or those had no response to treatment with P value 0.053. In contrast to Gouda et al [22] who found no statistical significance regarding the disease outcome which may be explained in the previous study by the relatively high percentage (34%) of inaccessible information's during the follow up period.…”

“…This was in agreement with the study of Diao et al [21] as in his study the polymorphic variants were significantly associated with greater tumor cell invasion (stages III and IV). Another former study reported similar results where the polymorphic variants of MMP-2 were more frequent in patients with advanced clinical stages (III, IV) (22].On the other hand Zhou et al [24] noted that genotype CC of -735C/T was associated with increased MMP-2 expression and greater risk of invasion and metastasis of esophageal and lung cancer. On the other hand, Rollin et al [25] exhibited that in cancer lung MMP-2 gene expression was less in the CC genotype compared to other genotypes (CT/TT).…”

Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells

“…MMP-2 and MMP-9 are the unique types of proteinase that hydrolyze the bone structure of excellular matrix (type IV collagen). Thereby, they are particularly correlated with tumor metastasis [ 39 - 41 ]. Here, we found that resistin increased MMP-2 expression, however, resistin only slightly enhanced MMP-9 production (data not shown).…”

Securin promotes migration and invasion via matrix metalloproteinases in glioma cells

“…Under physiological conditions, MMP expression is low in the majority of normal cells. By contrast, MMP expression is markedly increased in a number of different cancers (15,16) and is directly associated with tumor invasiveness (17), which contributes to poor patient outcomes. As two important members of the MMP family, MMP2 and MMP9 have been identified to be involved in colon cancer progression, hepatic metastasis (18), the promotion of lung cancer invasion (19), and hepatocellular carcinoma cell migration and invasion (20).…”