MMP 9 Gene Promoter Polymorphism in Gastric Cancer

Abstract

Matrix metalloproteinase-9 (gelatinase B) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C) > thymidine (T) single nucleotide polymorphism (SNP) at position -1562 in the MMP-9 promoter is reported to influence the expression of the gene. Genotyping of MMP-9 -1562 C→T promoter polymorphism in 140 gastric cancer patients and 132 healthy control subjects was carried out in order to evaluate its association with progression and development of gastric cancer. The SNP was genotyped by tetra-primer amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. Statistical methods were adopted to test for the significance of the results. Risk factor profile of the patients revealed age above 50 years, smoking, alcoholism as the factors associated with the disease. The distribution of genotype frequencies in gastric cancer patients were 28.7 % of CC, 45.5 % of CT and 25.7 % of TT, whereas in control subjects 31.8 % of CC, 53.03 % of CT and 15.15 % of TT, respectively. The allelic frequencies were 51.51 % of C and 48.48 % of T in patient group and 58.33 % of C and 41.66 % of T in controls respectively. The present study shows the possible association of epidemiological risk factors with gastric cancer. There is an increased frequency of T allele in the disease compared to control subjects. However, there is no association of the MMP-9 -1562 C→T promoter polymorphism in the development of gastric cancer.

Genetic variation of MMP‐2(‐735 C>T) and MMP‐9(‐1562 C>T) gene in risk of development of HAND and severity of HAND

“…In the present study, the frequencies of MMP‐2 ‐735C > T polymorphisms of healthy controls were comparable with those from a previous study in North India, although they differed from those of another study in North India . The frequencies of the MMP‐9 ‐1562C > T polymorphism of healthy controls were comparable with a North Indian study and differed from those in a South Indiam study …”

“…32 The frequencies of the MMP-9-1562C > T polymorphism of healthy controls were comparable with a North Indian study 33 and differed from those in a South Indiam study. 34 In the present study, individuals with CT genotypes and the T allele of MMP-2 had a reduced risk of severe HAND. A C > T transition of the -735C/T polymorphism disrupts the core recognition sequence of the Sp1 site (CCACC box), which displays lower promoter activity for the T allele.…”

Matrix metalloproteinase 9 gene polymorphisms are associated with a multiple family history of gastric cancer

“…The T allele of MMP9 -1562 is associated with elevated MMP-9 plasma concentration [32] in accordance with the increased promoter activity of the -1562T allele [33]. As a result, MMP9 C-1562T is associated with susceptibility to GC [34]. On the other hand, MMP9 R668Q is located in the hemopexin-like domain, which is necessary for the collagenase activity of MMP-9 [35], and is associated with survival in lung cancer [36] and melanoma [37].…”

The association of matrix metalloproteinase-9 promoter polymorphisms with gastric cancer risk: a meta-analysis

“…In addition, these Chinese researchers [ 4 ] found that the genotype of MMP-9 is correlated with TNM classification and lymph node metastasis and plays an important role in the progression and metastasis of gastric cancer. In contrast to the abovementioned investigation, two additional studies published by Chinese researchers [ 6 , 7 ], one additional study published by Indian researchers [ 8 ], and one study published by Turkish researchers [ 9 ] suggest no relevant association of MMP-9 with gastric cancer. Therefore, we conducted this meta-analysis to verify the association of MMP-9 SNPs with the risk of GC.…”

“…The best possible score of this scale is 9 points. In this meta-analysis, two studies [ 3 , 13 ] scored 8 points; six studies [ 4 – 6 , 8 , 9 , 14 ] scored 7 points; and one study [ 7 ] scored 6 points.…”