Dataset Information

Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley.

ABSTRACT: BACKGROUND/AIM: Degradation of the basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with a broad substrate specificity, and its expression has been shown to be associated with tumor invasion and metastasis for various cancers. PATIENTS AND METHODS: To document the role of MMP-7 polymorphism in esophageal carcinogenesis, a case-control study was performed comprising 135 patients with esophageal cancer (EC) and 195 healthy controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were statistically analyzed using ?2 - test and logistic regression models. RESULTS: Carriers for the MMP-7 (-181A>G) GG were associated with an increased risk for EC [odds ratio (OR = 2.17; 95% confidence interval (CI) = 1.21-3.92; P = 0.010; P-trend = 0.04]. Also, in a recessive model, our results showed that MMP-7 (-181A>G) GG allele conferred significantly higher risk for EC (OR =2.16; 95% CI = 1.31-3.54; P = 0.003). The high risk due to MMP-7 (-181GG) genotype was limited to squamous cell histology of EC (OR = 2.41; 95% CI = 1.27-4.56; P = 0.007). Although smoking (Hukka) and high consumption of salted tea are independent risk factors for EC, the interaction of MMP-7 (-181A>G) genotypes with these factors did not further modulate the risk of EC. CONCLUSIONS: In conclusion, our results show that MMP-7 (-181A>G) GG carriers are at a higher risk of esophageal squamous cell carcinoma in Kashmir valley.

SUBMITTER: Malik MA

PROVIDER: S-EPMC3178916 | biostudies-literature | 2011 Sep-Oct

REPOSITORIES: biostudies-literature

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Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley.

Malik Manzoor A MA Sharma Kiran L KL Zargar Showket A SA Mittal Balraj B

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 20110901 5

<h4>Background/aim</h4>Degradation of the basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with a broad substrate specificity, and its expression has been shown to be associated with tumor invasion and metastasis for various cancers.<h4>Patients and methods</h4>To document the role of MMP-7 polymorphism ...[more]

PMID: 21912055

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Project description:BackgroundThe 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 methodsA 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.ResultsThe 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.ConclusionA significant increase in ESCC risk is associated with the SNPs CDKN1A rs1059234 and MMP9 rs17576.

Project description:ContextThe exact factors that determine the biological behavior of odontogenic lesions have not been thoroughly established yet. The influence of the matrix metalloproteinases (MMPs) on the clinical behavior of these lesions was recently brought to light.AimsWe did a pioneer study to investigate the association of MMP9 (rs3918242 [-1562 C/T] and rs17576) and MMP2 (rs243865 [-1306 C/T] and rs865094) gene polymorphisms and aggressiveness of ameloblastomas, keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC).Settings and designA case-control study conducted in the Department of Oral Pathology and Microbiology, Government Dental College, Trivandrum and Human Molecular Genetics Laboratory, Rajiv Gandhi Institute of Biotechnology and Poojappura, Trivandrum, Kerala.Subjects and methodsDNA from the blood samples of histopathologically proven ameloblastoma (n = 15), KCOT (n = 11) and DC (n = 13) patients were extracted using standard protocols. Primers were designed based on the functionality and relevance for polymerase chain reaction (PCR). PCR products were analyzed by PCR-restriction fragment length polymorphism and sequencing.Statistical analysis usedChi-square analysis was done to assess the association of gene polymorphisms among the cases and controls.ResultsAmeloblastomas showed a higher frequency of mutant allele (T = 0.43; P = 0.05) of MMP9 rs3918242 (-1562C/T) compared to the control population. All the cases showed a statistically significant difference in the distribution of genotype (P = 0.046) and allele (P = 0.03; odds ratio [OR] = 2.06 [1.08-3.95]) frequency of MMP2 rs2438659 (-1306C/T). KCOT samples also showed a significant association in distribution of both genotype (P = 0.01) and allele (P = 0.01 with an OR at 3.42 [1.31-8.92]) frequency, on comparison with control population.ConclusionsMMP2 rs243865 polymorphism has a plausible role in increasing the aggressiveness of ameloblastomas and KCOT compared to that of the control population. Furthermore, MMP9 rs3918242 polymorphism may contribute to the aggressive behavior of ameloblastomas.

Dataset Information

Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley.

Publications

Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley.

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