Saudi Journal of Gastroenterology
Home About us Instructions Submission Subscribe Advertise Contact Login    Print this page  Email this page Small font sizeDefault font sizeIncrease font size 
Users Online: 713 

Table of Contents   
Year : 2011  |  Volume : 17  |  Issue : 5  |  Page : 301-306
Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley

1 Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
2 Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India

Click here for correspondence address and email

Date of Submission13-Dec-2010
Date of Acceptance11-Feb-2011
Date of Web Publication6-Sep-2011


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 χ2 - 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.

Keywords: Esophageal cancer, Kashmir valley, MMP-7 (−181A>G) polymorphism

How to cite this article:
Malik MA, Sharma KL, Zargar SA, Mittal B. Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley. Saudi J Gastroenterol 2011;17:301-6

How to cite this URL:
Malik MA, Sharma KL, Zargar SA, Mittal B. Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley. Saudi J Gastroenterol [serial online] 2011 [cited 2022 Dec 8];17:301-6. Available from:

Esophageal cancer (EC) is the most aggressive malignant tumor of the gastrointestinal tract. EC is the eighth most commonly occurring cancer in the world. [1] Within the Indian subcontinent, the valley of Kashmir presents a strikingly different picture where the incidence of EC has been reported to exceed 40% of all cancers and is 3-6 times higher than various metropolis cancer registries in India. [2] Some of the genetic and environment factors have been reported to be associated with an increased risk of EC in Kashmir valley. [3],[4],[5]

Matrix metalloproteinases (MMPs) are a family of enzymes responsible for the breakdown of connective tissue proteins. These enzymes play an important role in tissue remodelling associated with growth, development, and repair. In these physiological processes, MMP activity is tightly regulated. However, it is clear that aberrant MMP expression can contribute to the pathogenesis of several diseases including rheumatoid arthritis, multiple sclerosis, cerebral hemorrhage, and inflammatory bowel disease. Matrix metalloproteinase-7 (MMP-7) is one of the MMP family members and consists of a primordial form of these members. [6] It can degrade laminin, type IV collagen, and entactin, [7],[8],[9] which are the main components of the basement membrane, and activate other important MMPs (eg, MMP-1, MMP-2, and MMP-9). [10],[11] It can also inactivate α1-antitrypsin, which augments the serine protease activity, and thus indirectly activates MMPs. [12]

The gene encoding MMP-7 is localized on chromosome 11q21-q22. Two polymorphisms exist in the MMP-7 promoter region, -181A>G and −153C>T, which are known to modify the gene transcription activity. [13],[14] Previous studies have shown association of MMP-7 (-181A>G) (rs11568818) polymorphisms with esophageal gastric and other malignancies. [15],[16],[17],[18],[19],[20],[21] However, till date, no study has been carried out to evaluate the role of MMP7 -181A>G polymorphism in relation to higher prevalence of EC in Kashmir valley, a high-risk population bordering the EC belt, known for high incidence of EC. Therefore, the aim of the present study was to investigate the role of MMP-7 (−181A>G) (rs11568818) in conferring genetic susceptibility to EC in the Kashmir valley.

   Patients and Methods Top

Study population

The present case/control study comprised untreated histopathologically confirmed cases with EC (135) and healthy controls (195). The sample size of the present study was adequate to provide 80% power. All subjects were unrelated permanent residents of Kashmir and were referred from the departments of gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, from May 2006 to December 2008. Patients and controls were matched by ethnicity, mean age, and gender. Patients were excluded if they had non-malignant conditions such as corrosive esophageal injury, achalasia injury, Barrett's esophagus, gastro-esophageal reflux disease (GERD), and non-ulcer dyspepsia. Controls were also recruited from Sher-i-Kashmir Institute of Medical Sciences, Srinagar. Healthy controls were individuals who came for their routine health checkups or minor illness such as fever, common headache, or minor surgery. They were ethnicity matched with cases, free from any chronic disease, unrelated to patients, and having similar socioeconomic background. All individuals were personally interviewed about their age, occupational history, medical history of other diseases, demographic features, family history of cancer, use of hot noon chai (salted tea), drinking alcohol, and smoking habits. Tobacco use included smoking cigarettes or Hukka (water pipe). Written informed consent was obtained from all study participants. The research protocol was approved by the ethics committee of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow (project number: 5/13/48/2002-NCDIII).

Sample collection and preparation

Sample collection, storage, and transport were in compliance with committee guidelines. Blood samples were collected in ethylenediaminetetraacetic acid (EDTA) and genomic DNA was extracted from peripheral blood leukocyte pellet using the standard salting-out method. [22] The quality and quantity of DNA were checked by gel electrophoresis and spectrophotometry using Nanodrop Analyser (ND-1000) spectrophotometer (Nano Drop Technologies, Inc., Wilmington, DE, USA). The ratio of absorbance at 260 and 280 nm of DNA was approximately 1.7-1.9. The isolated DNA was stored at −70°C.


The MMP-7 polymorphism (−181A>G) was genotyped in subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Primers for amplification of MMP-7 (−181A>G) were taken as described. [14] PCR products were digested by the restriction endonuclease EcoR1 (Bangalore Genei) at 37°C overnight. The amplified fragments were separated on 15% polyacrylamide gel and visualized by ethidium bromide staining. Briefly, genotypes of MMP-7 were assigned as follows: 120 bp and 30 bp for −181GG; 150 bp, 120 bp, and 30 bp for −181AG; and 150 bp for −181AA genotype. More than 15% of the samples from patients and controls including samples of each genotype were re-genotyped by other laboratory personnel, but no discrepancy was found and the results were 100% concordant.

Statistical analysis

Demographic characteristics of patients and controls were described as frequencies and percentages, whereas descriptive statistics of patients and controls were presented as mean and standard deviations for continuous measures. Statistical significance of frequency differences between patients and control groups was evaluated using the χ2 test. Deviation from the Hardy-Weinberg equilibrium (HWE) in controls was assessed using the χ2 test; P value was considered significant at <0.05 level. Risk estimates were calculated for dominant and recessive genetic models using the most common homozygous genotype as reference. Observed genotype frequencies for MMP-7 (-181A>G) polymorphism (rs17878362) in controls were examined for deviation from HWE by using a goodness-of-fit χ2 -test with one degree of freedom. The single control group was used for analyzing two sets of cancer cases, ie, esophageal and gastric cancer. Binary logistic regression analysis was used to fit statistical models to predict the association of MMP-7 (-181A>G) genotypes with susceptibility to EC. Association was expressed as odds ratio (OR) for risk estimation with 95% confidence interval (95% CI). Bonferroni correction was applied in case of multiple comparisons using the formula pc = p Χ n (where, pc represents corrected value, and n is the number of comparisons performed). All analyses were performed using the SPSS statistical analysis software, version 15.0 (SPSS, Chicago, IL, USA).

   Results Top

Population characteristics

The mean age of healthy subjects (controls) and patients with EC was 57.98 ± 12.67 and 60.38 ± 8.41 years, respectively (t test P = ns). EC was highly prevalent in males (68.1%) than in females. In patients with EC, squamous cell carcinoma (SCC) histopathology was common (76.3%). Smoking habit (Hukka) showed a significantly higher risk in EC (OR =21.45; 95% CI =11.63-39.55; P = 0.0001) patients. Individuals consumed salted-tea in a range of 2-8 cups per day; and median consumption of tea was 4 cups per day. So, we grouped individuals in to ≤4 cups or >4 cups per day and individuals consumed salted tea >4 cups per day were regarded as high salted tea consumers. Higher consumption of salted tea was also found to be associated with increased risk of EC (OR =14.86; 95% CI =8.42-26.25; P = 0.0001) [Table 1]. None of the patients or controls reported consumption of alcohol, so interaction of alcohol intake with genetic variations could not be analyzed.
Table 1: Demographic characteristics of study subjects

Click here to view

Association of genetic variant of MMP-7 (-181A>G) polymorphism with susceptibility to EC

The genotype frequencies of the MMP-7 (-181A>G) polymorphism among cases and controls are shown in [Table 2]. The observed genotype frequencies among the control subjects were in agreement with the HWE (P = 0.55; χ2 = 0.37). In the present study, when we used the MMP 7 (-181A>G) AA genotype as reference, we found that individuals with MMP-7 (-181A>G) GG genotype were significantly associated with more than twofold increased risk of EC (OR =2.17; 95% CI =1.21-3.92; P = 0.010; P-trend = 0.04) as compared with the control group. Moreover, in the recessive model, our results showed that MMP-7 (-181A>G) GG genotype conferred significantly increased risk for EC (OR =2.16; 95% CI =1.31-3.54; P = 0.003) [Table 2].
Table 2: Frequency distribution of genotypes and of MMP-7 (−181A>G) genotypes with risk of esophageal cancer

Click here to view

Association of MMP-7 (-181A>G) genotypes with tumor histopathology

When tumor histopathologies were analyzed, MMP-7 (-181A>G) GG genotype was found to be significantly associated with an increased risk for esophageal SCC (ESCC) (OR =2.41; 95% CI =1.27-4.56; P = 0.007) [Table 3]. However, we did not find a significant association in adenocarcinomas of esophagus cancer.
Table 3: Association of MMP-7 (−181A>G) genotypes with tumor histopathology and risk of esophageal cancer

Click here to view

Interaction of MMP-7 (-181A>G) genotypes with environmental factors

Our results show significant association of high consumption of salted tea and smoking with EC [Table 1]. However, in gene-environment interaction, we did not find any significant modulation of cancer risk by MMP-7 (-181A>G) genotypes with salted tea and smoking [Table 4] and [Table 5].
Table 4: Interaction of MMP-7 (−181A>G) genotypes with salted tea

Click here to view
Table 5: Interaction of MMP-7 (−181A>G) genotypes with smoking

Click here to view

   Discussion Top

MMPs are a class of proteases that contribute significantly and uniquely to the tumor microenvironment, which provides the elements needed for advanced tumor growth (i.e., cytokines, loss of contact inhibition, angiogenesis, and invasion). Overexpression of matrilysin (MMP-7) is predominantly associated with epithelial pre-malignant cells. [23]

In the present study, we looked for the effect of MMP- 7 (-181A>G) promoter polymorphism on the genetic susceptibility to EC. Based on the presented results, we report an association of MMP-7 (-181A>G) GG genotype with increased EC risk at genotype level as well as in the recessive model, suggesting that this polymorphism contributes to enhanced susceptibility for EC in Kashmir valley. Our results are supported by previously reported studies suggesting an association of MMP-7 (-181A>G) GG genotypes with an increased risk of various cancers with controversies. [17],[18],[19],[20],[21],[24],[25],[26],[27],[28],[29],[30],[31],[32] i.e.

in some populations GG genotypes are associated with the diease while in others no associations was found. The association of MMP-7 (-181A>G) polymorphism with cancer has been observed in Asians and not in Europeans. [19] Thus, there may be ethnic and geographical differences in the influence of MMP-7 (-181A>G) on the susceptibility of various cancers.

Previous reports have shown different etiologies and genetic risk factors for two histological types of EC. In the present study, MMP-7 (-181A>G) GG genotype was significantly associated with an increased risk for only squamous-type EC. Some other studies have also shown positive association of MMP-7 (-181A>G) GG with SCC. [15],[16],[17],[24] Wu et al.[33] have reported that MMP-7 is highly expressed in metastatic cervical SCC, and may serve as a marker in estimating the invasive and metastatic potential of cervical SCC.

The underlying mechanism of this association may be related to the promoter activity variation of the −181G alleles. Functional analysis has shown that MMP-7-181G alleles can increase gene transcription activity. [14] The expression and promoter activity of the MMP-7-181G allele is twofold to threefold higher than the −181A allele due to presence of a putative binding site (NGAAN) for a heat-shock transcription factor. [14] The presence of high-expression MMP-7-181G allele may alter the cell surface signaling including cellular proliferation, invasion, and apoptosis processes. [34] Therefore, individuals with excess MMP-7 activity by harboring the −181G allele may be predisposed to malignant transformation. Although in vitro studies have suggested that the −153C/T polymorphism (another polymorphism in the promoter region) may also modify promoter activity of the MMP-7 gene, we did not evaluate its role in EC development because of low frequency of the −153T allele in the study population. The higher promoter activity of the −181G allele may induce elevation of the MMP-7 mRNA and, subsequently, increase protein expression. Individuals with excess MMP-7 activity by harboring the −181G allele may predispose to malignant transformation through the 'sheddase' activity of MMP-7 protein via recently described substrates such as tumor necrosis factor A, E-cadherin, and Fas ligands. These substrates have been known to play important roles in signal transduction, cell-cell adhesion, and apoptosis [35],[36],[37],[38] In addition, elevated expression of MMP-7 induced by the −181G allele may lead to increased activation of other members of the MMP family such as MMP-2. [39] The latter may therefore modulate tumor development via regulating cancer cell growth, angiogenesis, and immune surveillance. [40]

Gu et al.[41] reported that the high expression of MMPs in the invasive margin may help degrade the extracellular matrix surrounding ESCC cells, thereby facilitating the invasion or metastasis of this malignancy.

The people residing in the Kashmir valley have several unique dietary features, which are different from the rest of the world. Salted tea used by people is prepared by using baking soda (sodium bicarbonate) along with common salt (sodium chloride) and boiled for few hours before consuming. It is suspected that the salts might cause thermal injury to the esophageal and gastric epithelia. [2] In the present study, high consumption of salted tea (>4 cups a day) was independently associated with an increased risk for EC (OR =14.86; P = 0.0001). Similarly, significant association of smoking (Hukka) with EC (OR =21.45; P = 0.0001). An association between drinking large amounts of hot salted tea and enhanced risk of EC has been reported in other studies, which have been attributed to thermal irritation of the oesophageal and gastric mucosa by the hot drink. [42],[43] However, based on our gene-environment interactions, after Bonferroni correction, we did not find any significant modulation of cancer risk due to interaction of MMP-7 (-181A>G) genotypes with smoking or salted tea consumption.

The sample size of the present study was adequate to provide 80% power for overall association. Because the sample size became smaller in subgroup analyses, we applied Bonferroni correction for multiple comparisons. Moreover, this is the first report of genetic susceptibility of EC due to MMP-7 (-181A>G) gene polymorphism in the Kashmir valley. In conclusion, our data suggest that the MMP-7 (-181A>G) gene polymorphism may influence the susceptibility to ESCC. Determination of MMP-7 (−181A>G) genotype may provide a useful genetic marker in predicating high-risk individuals for the development of EC. However, it may be worthwhile to conduct additional population-based studies including a large subject group before its clinical application.

   Acknowledgments Top

The study was supported by a research grant from the Indian Council of Medical Research, New Delhi. The authors thank all faculty members of the Gastroenterology Department, SKIMS, Srinagar, for their help in sample collection.

   References Top

1.Parkin DM. The role of cancer registries in cancer control. Int J Clin Oncol 2008;13:102-11.  Back to cited text no. 1
2.Khuroo MS, Zargar SA, Mahajan R, Banday MA. High incidence of oesophageal and gastric cancer in Kashmir in a population with special personal and dietary habits. Gut 1992;33:11-5.  Back to cited text no. 2
3.Siddiqi M, Kumar R, Fazili Z, Spiegelhalder B, Preussmann R. Increased exposure to dietary amines and nitrate in a population at high risk of oesophageal and gastric cancer in Kashmir (India). Carcinogenesis 1992;13:1331-5.  Back to cited text no. 3
4.Malik MA, Upadhyay R, Mittal RD, Zargar SA, Modi DR, Mittal B. Role of xenobiotic-metabolizing enzyme gene polymorphisms and interactions with environmental factors in susceptibility to gastric cancer in Kashmir Valley. J Gastrointest Cancer 2009a;40:26-32.  Back to cited text no. 4
5.Malik MA, Upadhyay R, Modi DR, Zargar SA, Mittal B. Association of NAT2 gene polymorphisms with susceptibility to esophageal and gastric cancers in the Kashmir Valley. Arch Med Res 2009b;40:416-23.  Back to cited text no. 5
6.Brown PD. Matrix metalloproteinases in gastrointestinal cancer. Gut 1998;43:161-3.  Back to cited text no. 6
7.Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Noboru N, et al. Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymatic properties. J Biol Chem 1995;270:6691-7.  Back to cited text no. 7
8.Murphy G, Cocket M, Ward R, Docherty AJ. Matrix metalloproteinase degradation of elastin, type IV collagen, and proteoglycan: A quantitative comparison of the activities of 95 kDa and 72 kDa gelatinases, stromelysin-1 and −2 and punctuated metalloproteinase (PUMP). Biochem J 1991;277:277-9.  Back to cited text no. 8
9.Sires UI, Griffin GL, Broekelmann TJ, Mecham RP, Murphy G, Chung AE, et al. Degradation of entactin by matrix metalloproteinases. Susceptibility to matrilysin and identification of cleavage sites. J Biol Chem 1993;268:2069-74.  Back to cited text no. 9
10.Crabbe T, Smith B, O'Connell J, Docherty A. Human progelatinase A can be activated by matrilysin. FEBS Lett 1994;345:14-6.  Back to cited text no. 10
11.Sang QA, Bodden MK, Windsor LJ. Activation of human progelatinase A by collagenase and matrilysin: Activation of procollagenase by matrilysin. J Protein Chem 1996;15:243-53.  Back to cited text no. 11
12.Sires UI, Murphy G, Baragi VM, Fliszar C, Welgus HG, Senior RM. Matrilysin is much more efficient than other matrix metalloproteinases in the proteolytic inactivation of a1-antitrypsin. Biochem Biophys Res Commun 1994;204:613-20.  Back to cited text no. 12
13.Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: Increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res 2004;10:2832-45.  Back to cited text no. 13
14.Jormsjö S, Whatling C, Walter DH, Zeiher AM, Hamsten A, Eriksson P. Allelespecific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2001;21:1834-9.  Back to cited text no. 14
15.Murray GI, Duncan ME, O'Neil P, McKay JA, Melvin WT, Fothergill JE. Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer. J Pathol 1998;185:256-61.  Back to cited text no. 15
16.Etoh T, Inoue H, Yoshikawa Y, Barnard GF, Kitano S, Mori M. Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness. Gut 2000;47:50-6.  Back to cited text no. 16
17.Zhang J, Jin X, fang S, Wang R, Li Y, Wang N, et al. The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma. Carcinogenesis 2005;26:1748-53.  Back to cited text no. 17
18.Yeh YC, Sheu BS, Cheng HC, Wang YL, Yang HB, Wu JJ. Elevated serum matrix metalloproteinase-3 and −7 in H. pylori-related gastric cancer can be biomarkers correlating with a poor survival. Dig Dis Sci 2010;55:1649-57.  Back to cited text no. 18
19.Peng B, Cao L, Ma X, Wang W, Wang D, Yu L. Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk. Mutagenesis 2010;25:371-9.  Back to cited text no. 19
20.Hellmig S, Ott S, Rosenstiel P, Robert UF, Hampe J, Schreiber S. Genetic variants in matrixmetalloproteinase genes are associated with development of gastric ulcer in H. pylori infection. Am J Gastroenterol 2006;101:29-35.  Back to cited text no. 20
21.Vairaktaris E, Serefoglou Z, Yapijakis C, Vylliotis A, Nkenke E, Derka S, et al. High gene expression of matrix metalloproteinase-7 is associated with early stages of oral cancer. Anticancer Res 2007;27:2493-8.  Back to cited text no. 21
22.Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.  Back to cited text no. 22
23.Bjorklund M, Koivunen E. Gelatinasemediated migration and invasion of cancer cells. Biochim Biophys Acta 2005;1755:37-69.  Back to cited text no. 23
24.Yamashita K, Mori M, Shiraishi T, Shibuta K, Sugimachi K. Clinical significance of matrix metalloproteinase-7 in esophageal carcinoma. Clin Cancer Res 2000;6:1169-74.  Back to cited text no. 24
25.Li Y, Jin X, Kang S, Wang Y, Du H, Zhang J, et al. Polymorphisms in the promoter regions of the matrix metalloproteinases-1, -3, -7, and −9 and the risk of epithelial ovarian cancer in China. Gynecol Oncol 2006;101:92-6.  Back to cited text no. 25
26.Ghilardi G, Biondi ML, Erario M, Guagnellini E, Scorza1 R. Colorectal carcinoma susceptibility and metastases are associated with matrix metalloproteinase-7 promoter polymorphisms. Clin Chem 2003;49:1940-2.  Back to cited text no. 26
27.Singh H, Jain M, Mittal B. MMP-7 (-181A>G) promoter polymorphisms and risk for cervical cancer. Gynecol Oncol. 2008;110:71-5.  Back to cited text no. 27
28.Srivastava P, Gangwar R, Kapoor R, Mittal RD. Bladder cancer risk associated with genotypic polymorphism of the matrix metalloproteinase-1 and 7 in North Indian population. Dis Markers. 2010;29:37-46.  Back to cited text no. 28
29.Beeghly-Fadiel A, Shu XO, Long J, Li C, Cai Q, Cai H, et al. Genetic polymorphisms in the MMP-7 gene and breast cancer survival. Int J Cancer 2009;124:208-14.  Back to cited text no. 29
30.Lièvre A, Milet J, Carayol J, Le Corre D, Milan C, Pariente A, et al. Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma. BMC Cancer 2006;6:270.  Back to cited text no. 30
31.Beeghly-Fadiel A, Long JR, Gao YT, Li C, Qu S, Cai Q, et al. Common MMP-7 polymorphisms and breast cancer susceptibility: A multistage study of association and functionality. Cancer Res 2008;68:6453-9.  Back to cited text no. 31
32.Dos Reis ST, Pontes J Jr, Villanova FE, Borra PM, Antunes AA, Dall'oglio MF, et al. Genetic polymorphisms of matrix metalloproteinases: Susceptibility and prognostic implications for prostate cancer. J Urol 2009;181:2320-5.  Back to cited text no. 32
33.Wu SH, Zhang J, Li Y, Li JM. Expression of ETV5 and MMP-7 in early stage cervical squamous cell carcinoma and its role in lymphatic metastasis. Ai Zheng 2006;25:315-9.  Back to cited text no. 33
34.Yu WH, Woessner JF, McNeish JD, Stamenkovic I. CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 2002;16:307-23.  Back to cited text no. 34
35.Noe V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, et al. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci 2001;114:111-8.  Back to cited text no. 35
36.Powell WC, Fingleton B, Wilson CL, Boothby M, Matrisian LM. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr Biol 1999;9:1441-7.  Back to cited text no. 36
37.Gumbiner BM. Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 1996;84:345-57.  Back to cited text no. 37
38.Vargo-Gogola T, Fingleton B, Crawford HC, Matrisian LM. Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo. Cancer Res 2002;62:5559-63.  Back to cited text no. 38
39.Barille S, Bataille R, Rapp MJ, Harousseau JL, Amiot M. Production of metalloproteinase-7 (matrilysin) by human myeloma cells and its potential involvement in metalloproteinase-2 activation. J Immunol 1999;163:5723-8.  Back to cited text no. 39
40.Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002;2:161-74.  Back to cited text no. 40
41.Gu ZD, Li JY, Li M, Gu J, Shi XT, Ke Y, et al. Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma. Am J Gastroenterol 2005;100:1835-43.  Back to cited text no. 41
42.Islami F, Boffetta P, Ren JS, Pedoeim L, Khatib D, Kamangar F. High-temperature beverages and foods and esophageal cancer risk - a systematic review. Int J Cancer 2009;125:491-524.  Back to cited text no. 42
43.Correa P. Modulation of gastric carcinogenesis: Updated model based on intragastric nitrosation. IARC Sci Publ 1987;84:485-91.  Back to cited text no. 43

Correspondence Address:
Balraj Mittal
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow - 226 014
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-3767.84480

Rights and Permissions


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

This article has been cited by
1 Polymorphisms of matrix metalloproteinases affect the susceptibility of esophageal cancer
Hai Chen, Xianquan Xu, Congshu Hua, Heng Zhang, Junling Jian, Tengfei Ge, Jianfeng Xie, Zaicheng Yu
Medicine. 2021; 100(38): e27229
[Pubmed] | [DOI]
2 Association of MMP7 -181A?G Promoter Polymorphism with Gastric Cancer Risk
Kousik Kesh, Lakshmi Subramanian, Nillu Ghosh, Vinayak Gupta, Arnab Gupta, Samir Bhattacharya, Nitish R. Mahapatra, Snehasikta Swarnakar
Journal of Biological Chemistry. 2015; 290(23): 14391
[Pubmed] | [DOI]
3 Reply: False positive result in study on hookah smoking and cancer in Kashmir: measuring risk of poor hygiene is not the same as measuring risk of inhaling water-filtered tobacco smoke all over the world
N A Dar,F Islami,P Boffetta
British Journal of Cancer. 2013; 108(6): 1391
[Pubmed] | [DOI]
4 Socioeconomic status and esophageal squamous cell carcinoma risk in Kashmir, India
Nazir A. Dar,Idrees A. Shah,Gulzar A. Bhat,Muzamil A. Makhdoomi,Beenish Iqbal,Rumaisa Rafiq,Iqra Nisar,Arshid B. Bhat,Sumaiya Nabi,Akbar Masood,Sajad A. Shah,Mohd M. Lone,Showkat A. Zargar,Farhad Islami,Paolo Boffetta
Cancer Science. 2013; 104(9): 1231
[Pubmed] | [DOI]
5 Matrix metalloproteinase7 -181A/G polymorphism is associated with increased cancer risk among high-quality studies: Evidence from a meta-analysis
Jing Wu,Xuan Guan,Ya-Ting Li,Peng Bai,Jin Wu
Clinical Biochemistry. 2013; 46(16-17): 1649
[Pubmed] | [DOI]
6 Update meta-analysis on MMP-7 -181A>G polymorphism and cancer risk: Evidence from 25 studies
Xueling Yang,Ya Liu,Yufeng Yang,Bo Li
Gene. 2013; 521(2): 252
[Pubmed] | [DOI]
7 Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: An overview
Ajay Kumar Chaudhary,Shruti Pandya,Kanjaksha Ghosh,Anita Nadkarni
Mutation Research/Reviews in Mutation Research. 2013; 753(1): 7
[Pubmed] | [DOI]
8 Current evidence on associations between the MMP-7 (-181A>G) polymorphism and digestive system cancer risk
Ke, P. and Wu, Z.-D. and Wen, H.-S. and Ying, M.-X. and Long, H.-C. and Qing, L.-G.
Asian Pacific Journal of Cancer Prevention. 2013; 14(4): 2269-2272
9 Update meta-analysis on MMP-7 -181A>G polymorphism and cancer risk: Evidence from 25 studies
Yang, X. and Liu, Y. and Yang, Y. and Li, B.
Gene. 2013; 521(2): 252-258
10 Reply: False positive result in study on hookah smoking and cancer in Kashmir: Measuring risk of poor hygiene is not the same as measuring risk of inhaling water-filtered tobacco smoke all over the world
Dar, N.A. and Islami, F. and Boffetta, P.
British Journal of Cancer. 2013; 108(6): 1391-1392
11 Association between promoters polymorphisms of matrix metalloproteinases and risk of digestive cancers: a meta-analysis
Xiaoying Li,Lianxi Qu,Yu Zhong,Yingjie Zhao,Hongyan Chen,Lu Daru
Journal of Cancer Research and Clinical Oncology. 2013; 139(9): 1433
[Pubmed] | [DOI]
12 Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk
Pan Ke,Zhong-De Wu,Hua-Song Wen,Miao-Xiong Ying,Huo-Cheng Long,Liu-Guo Qing
Asian Pacific Journal of Cancer Prevention. 2013; 14(4): 2269
[Pubmed] | [DOI]
13 Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients
Avshesh Mishra,Anshika Srivastava,T. Mittal,N. Garg,B. Mittal
Clinica Chimica Acta. 2012; 413(19-20): 1668
[Pubmed] | [DOI]
14 Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India
Dar, N.A. and Bhat, G.A. and Shah, I.A. and Iqbal, B. and Kakhdoomi, M.A. and Nisar, I. and Rafiq, R. and Iqbal, S.T. and Bhat, A.B. and Nabi, S. and Shah, S.A. and Shafi, R. and Masood, A. and Lone, M.M. and Zargar, S.A. and Najar, M.S. and Islami, F. and Boffetta, P.
British Journal of Cancer. 2012; 107(9): 1618-1623
15 The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: Possible genetic and cell-signaling mechanisms
Quốc Luong, K.V. and Nguyên, L.T.H.
Cancer Management and Research. 2012; 4(1): 431-445
16 Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients
Mishra, A. and Srivastava, A. and Mittal, T. and Garg, N. and Mittal, B.
Clinica Chimica Acta. 2012; 413(19-20): 1668-1674
17 Higher risk of matrix metalloproteinase (MMP-2, 7, 9) and tissue inhibitor of metalloproteinase (TIMP-2) genetic variants to gallbladder cancer
Sharma, K.L. and Misra, S. and Kumar, A. and Mittal, B.
Liver International. 2012; 32(8): 1278-1286
18 Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India
N A Dar,G A Bhat,I A Shah,B Iqbal,M A Kakhdoomi,I Nisar,R Rafiq,S T Iqbal,A B Bhat,S Nabi,S A Shah,R Shafi,A Masood,M M Lone,S A Zargar,M S Najar,F Islami,P Boffetta
British Journal of Cancer. 2012; 107(9): 1618
[Pubmed] | [DOI]
19 Higher risk of matrix metalloproteinase (MMP-2, 7, 9) and tissue inhibitor of metalloproteinase (TIMP-2) genetic variants to gallbladder cancer
Kiran L. Sharma,Sanjeev Misra,Ashok Kumar,Balraj Mittal
Liver International. 2012; 32(8): 1278
[Pubmed] | [DOI]
20 MMP7 polymorphisms - A new tool in molecular pathology to understand esophageal cancer
Bavi, P., Bu, R., Uddin, S., Al-Kuraya, K.
Saudi Journal of Gastroenterology. 2011; 17(5): 299-300


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Patients and Methods
    Article Tables

 Article Access Statistics
    PDF Downloaded747    
    Comments [Add]    
    Cited by others 20    

Recommend this journal