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Nascimento GJFD, Silva LPD, Matos FRD, Silva TAD, Medeiros SRBD, Souza LBD, Freitas RDA. Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma. Braz Oral Res 2020; 35:e019. [PMID: 33237244 DOI: 10.1590/1807-3107bor-2021.vol35.0019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 06/08/2020] [Indexed: 01/25/2023] Open
Abstract
Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.
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Affiliation(s)
| | - Leorik Pereira da Silva
- Universidade Federal do Amazonas - UFAM, Health and Biotechnology Institute, Coari, AM, Brazil
| | | | | | | | - Lélia Batista de Souza
- Universidade Federal do Rio Grande do Norte - UFRN, Postgraduate Program in Oral Pathology, Natal, RN, Brazil
| | - Roseana de Almeida Freitas
- Universidade Federal do Rio Grande do Norte - UFRN, Postgraduate Program in Oral Pathology, Natal, RN, Brazil
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Vohra M, Sharma AR, Prabhu B N, Rai PS. SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review. Public Health Genomics 2020; 23:155-170. [PMID: 32966991 DOI: 10.1159/000510253] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 07/16/2020] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population migrations, genetic drift, and selection. Although there are a plethora of DNA sequence variations identified through genome-wide association studies (GWAS), the challenge remains to explain the mechanisms underlying interindividual phenotypic disparity accounting for disease susceptibility. Single nucleotide polymorphisms (SNPs) present in the sites for DNA methylation, transcription factor (TF) binding, or miRNA targets can alter the gene expression. The systematic review aimed to evaluate the complex crosstalk among SNPs, miRNAs, DNA methylation, and TFs for complex multifactorial disease risk. METHODS PubMed and Scopus databases were used from inception until May 15, 2019. Initially, screening of articles involved studies assessing the interaction of SNPs with TFs, DNA methylation, or miRNAs resulting in allele-specific gene expression in complex multifactorial diseases. We also included the studies which provided experimental validation of the interaction of SNPs with each of these factors. The results from various studies on multifactorial diseases were assessed. RESULTS A total of 11 articles for SNPs interacting with DNA methylation, 30 articles for SNPs interacting with TFs, and 11 articles for SNPs in miRNA binding sites were selected. The interactions of SNPs with epigenetic factors were found to be implicated in different types of cancers, autoimmune diseases, cardiovascular diseases, diabetes, and asthma. CONCLUSION The systematic review provides evidence for the interplay between genetic and epigenetic risk factors through allele-specific gene expression in various complex multifactorial diseases.
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Affiliation(s)
- Manik Vohra
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Anu Radha Sharma
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Navya Prabhu B
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Padmalatha S Rai
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India,
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Białkowska K, Marciniak W, Muszyńska M, Baszuk P, Gupta S, Jaworska-Bieniek K, Sukiennicki G, Durda K, Gromowski T, Lener M, Prajzendanc K, Łukomska A, Cybulski C, Huzarski T, Gronwald J, Dębniak T, Lubiński J, Jakubowska A. Polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13 and MT2A do not contribute to breast, lung and colon cancer risk in polish population. Hered Cancer Clin Pract 2020; 18:16. [PMID: 32765800 PMCID: PMC7395404 DOI: 10.1186/s13053-020-00147-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022] Open
Abstract
Background Matrix metalloproteinases (MMPs) and metallothioneins (MTs) are Zinc-related proteins which are involved in processes crucial for carcinogenesis such as angiogenesis, proliferation and apoptosis. Several single nucleotide polymorphisms (SNPs) in MMPs and MTs that affect genes expression have been associated with cancer risk, including breast, lung and colon. Methods The study group consisted of 648 unselected patients (299 with breast cancer, 199 with lung cancer, 150 with colon cancer) and 648 unaffected individuals. Five SNPs, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A were genotyped and serum zinc (Zn) level was measured. The cancer risk was calculated using multivariable logistic regression with respect to Zn. Results None of the 5 tested polymorphisms showed a correlation with cancer risk in studied groups, although for MMP-2, MMP-7 and MT2A non-significant differences in genotypes frequencies among cases and controls were observed. Conclusions Analyses of polymorphisms, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A in relation to serum Zn level did not show significant association with breast, lung and colon cancer risk among polish patients. Further studies are needed to verify this observation.
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Affiliation(s)
- Katarzyna Białkowska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | | | | | - Piotr Baszuk
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Satish Gupta
- Strand Life Sciences, Bangalore, Karnataka India
| | - Katarzyna Jaworska-Bieniek
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Grzegorz Sukiennicki
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Katarzyna Durda
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Tomasz Gromowski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Marcin Lener
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Karolina Prajzendanc
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Alicja Łukomska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Cezary Cybulski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Tomasz Huzarski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Jacek Gronwald
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Tadeusz Dębniak
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Jan Lubiński
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.,Read-Gene S.A., Grzepnica, Poland
| | - Anna Jakubowska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.,Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland
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Zare M, Jafari-Nedooshan J, Aghili K, Ahrar H, Jarahzadeh MH, Seifi-Shalamzari N, Zare-Shehneh M, Neamatzadeh H. ASSOCIATION OF MMP-7 -181A>G POLYMORPHISM WITH COLORECTAL CANCER AND GASTRIC CANCER SUSCEPTIBILITY: A SYSTEMATIC REVIEW AND META-ANALYSIS. ACTA ACUST UNITED AC 2019; 32:e1449. [PMID: 31644669 PMCID: PMC6812146 DOI: 10.1590/0102-672020190001e1449] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 01/16/2019] [Indexed: 02/06/2023]
Abstract
Introduction:
The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been
reported to be associated with colorectal cancer (CRC) and gastric cancer
(GC) susceptibility, yet the results of these previous results have been
inconsistent or controversial.
Aim:
To elaborate a meta-analysis to assess the association of -181A>G
polymorphism of MMP-7 with CRC and GC risk.
Methods:
Published literature evaluating the association from PubMed, Web of Science,
Google Scholar and other databases were retrieved up to April 25, 2018.
Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated
using random- or fixed-effects model.
Results:
A total of 19 case-control studies, which included eleven studies on CRC
(2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases
and 2,366 controls) were identified. There was a significant association
between MMP-7 -181A>G polymorphism and GC risk under the homozygote model
(GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model
(GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By
subgroup analysis based on ethnicity, an increased risk of CRC and GC was
found only among Asians.
Conclusions:
This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated
with GC risk, but not with CRC. However, our results clearly showed that the
MMP-7 -181A>G polymorphism significantly increased the risk of CRC only
in Asians.
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Affiliation(s)
- Mohammad Zare
- Shahid Sadoughi University of Medical Sciences, General Surgery
| | | | - Kazem Aghili
- Shahid Sadoughi University of Medical Sciences, Radiology
| | - Hossein Ahrar
- Shahid Sadoughi University of Medical Sciences, Radiology
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Tafrihi M, Golbabaei M, Shokrzadeh M. Association of the −181 G→A polymorphism in the MMP-7 gene promoter and gastric cancer: A case-control study. Meta Gene 2019. [DOI: 10.1016/j.mgene.2019.100594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Białkowska K, Marciniak W, Muszyńska M, Baszuk P, Gupta S, Jaworska-Bieniek K, Sukiennicki G, Durda K, Gromowski T, Prajzendanc K, Cybulski C, Huzarski T, Gronwald J, Dębniak T, Scott RJ, Lubiński J, Jakubowska A. Association of zinc level and polymorphism in MMP-7 gene with prostate cancer in Polish population. PLoS One 2018; 13:e0201065. [PMID: 30036379 PMCID: PMC6056054 DOI: 10.1371/journal.pone.0201065] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 07/07/2018] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Prostate cancer is one of the most commonly diagnosed malignancies among men in Western populations. Evidence reported in the literature suggests that zinc may be related to prostate cancer. In this study we evaluated the association of serum zinc levels and polymorphisms in genes encoding zinc-dependent proteins with prostate cancer in Poland. METHODS The study group consisted of 197 men affected with prostate cancer and 197 healthy men. Serum zinc levels were measured and 5 single nucleotide polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13, MT2A genes were genotyped. RESULTS The mean serum zinc level was higher in prostate cancer patients than in healthy controls (898.9±12.01 μg/l vs. 856.6±13.05 μg/l, p<0.01). When compared in quartiles a significant association of higher zinc concentration with the incidence of prostate cancer was observed. The highest OR (OR = 4.41, 95%CI 2.07-9.37, p<0.01) was observed in 3rd quartile (>853.0-973.9 μg/l). Among five analyzed genetic variants, rs11568818 in MMP-7 appeared to be correlated with 2-fold increased prostate cancer risk (OR = 2.39, 95% CI = 1.19-4.82, p = 0.015). CONCLUSION Our results suggest a significant correlation of higher serum zinc levels with the diagnosis of prostate cancer. The polymorphism rs11568818 in MMP-7 gene was also associated with an increased prostate cancer risk in Poland.
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Affiliation(s)
- Katarzyna Białkowska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | | | | | - Piotr Baszuk
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Satish Gupta
- Strand Life Sciences, Bangalore, Karnataka, India
| | - Katarzyna Jaworska-Bieniek
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Grzegorz Sukiennicki
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Katarzyna Durda
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Tomasz Gromowski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Karolina Prajzendanc
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Cezary Cybulski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Tomasz Huzarski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Jacek Gronwald
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Tadeusz Dębniak
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
| | - Rodney J Scott
- School of Biomedical Sciences, University of Newcastle, Newcastle, Australia.,Division of Molecular Medicine, NSW Health Pathology, Newcastle, Australia
| | - Jan Lubiński
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.,Read-Gene S.A., Grzepnica, Poland
| | - Anna Jakubowska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.,Independent laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland
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de Lima JM, de Souza LG, da Silva IDCG, Forones NM. E-Cadherin and Metalloproteinase-1 and -7 Polymorphisms in Colorectal Cancer. Int J Biol Markers 2018; 24:99-106. [DOI: 10.1177/172460080902400206] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Purpose E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC). Experimental design A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results Patients with the 1G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95%CI: 2.02–20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95%CI: 1.27–9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95%CI: 0.93–9.47, p=0.098). Conclusions The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis.
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Affiliation(s)
- Jacqueline Miranda de Lima
- Oncology Group, Gastroenterology Division, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo - Brazil
| | - Lessileia Gomes de Souza
- Oncology Group, Gastroenterology Division, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo - Brazil
| | | | - Nora Manoukian Forones
- Oncology Group, Gastroenterology Division, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo - Brazil
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Banday MZ, Sameer AS, Mir AH, Mokhdomi TA, Chowdri NA, Haq E. Matrix metalloproteinase (MMP) -2, -7 and -9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population - A case-control study and a mini review. Gene 2016; 589:81-89. [PMID: 27222481 DOI: 10.1016/j.gene.2016.05.028] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Revised: 04/12/2016] [Accepted: 05/17/2016] [Indexed: 12/11/2022]
Abstract
Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a pivotal role in the transformation and progression of tumors at all stages, especially during the invasion and metastasis. The aim of this study was to determine the genetic association of MMP2, MMP7 and MMP9 promoter polymorphisms with colorectal cancer (CRC) susceptibility and development risk in ethnic Kashmiri population. The genotype frequencies of MMP2-1306C/T, MMP7-181A/G and MMP9-1562C/T SNPs were compared between 142 CRC patients and 184 healthy controls by using PCR-RFLP method. The association between all the three MMP promoter polymorphisms and the modulation of risk of CRC was found to be significant (p≤0.05). The heterozygous genotype (CT) of MMP2-1306C/T SNP and variant genotype (GG) of MMP7-181A/G SNP showed a significant association with decreased risk for the development of CRC [OR, 0.61 (95%CI, 0.37-1.01); p=0.05 and OR, 0.43 (95%CI, 0.20-0.90); p=0.02, respectively] whereas the heterozygous genotype (CT) of MMP9-1562C/T SNP showed a significant association with increased risk for the development of colorectal cancer [OR, 1.88 (95%CI, 1.11-3.18); p=0.02]. Further, the less common MMP9-1562T allele was found to be significantly associated with an increased risk of colorectal cancer [OR, 1.74 (95%CI, 1.15-2.62); p=0.007]. Our results suggest that these MMP2, MMP7 and MMP9 promoter polymorphisms play a role as one of the key modulators of the risk of developing colorectal cancer in Kashmiri population.
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Affiliation(s)
- Mujeeb Zafar Banday
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India
| | - Aga Syed Sameer
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Ashaq Hussain Mir
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India
| | - Taseem A Mokhdomi
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India
| | - Nissar A Chowdri
- Department of Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Ehtishamul Haq
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India.
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Yari K, Rahimi Z, Payandeh M, Rahimi Z. MMP-7 A-181G Polymorphism in Breast Cancer Patients from Western Iran. Breast Care (Basel) 2015; 10:398-402. [PMID: 26989359 PMCID: PMC4789881 DOI: 10.1159/000442231] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) are upregulated in tumors. The MMP-7 A-181G polymorphism is associated with increased expression of the MMP-7 gene. Aim of the present study was to investigate the association between the MMP-7 A-181G polymorphism and susceptibility to breast cancer. PATIENTS AND METHODS The MMP-7 A-181G variants were studied in a cohort of 251 subjects consisting of 100 breast cancer patients and 151 healthy controls; all were from Western Iran. The MMP-7 A-181G genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS The frequencies of the MMP-7 AA, AG, and GG genotypes in healthy individuals were 34.4, 50.4, and 15.2%, respectively. In breast cancer patients, the frequencies of AA (34%), AG (52%), and GG (14%) genotypes (p = 0.95) were similar to those in the controls. There was a trend toward an increased frequency of the combined genotype of MMP-7 AG+GG in patients with lymph node metastasis (70.4%) compared to those without metastasis (66.7%). Also, in patients with invasive lobular carcinoma, the frequency of the MMP-7 AG+GG genotype tended to be higher (71.4%) compared to that in patients with invasive ductal carcinoma (66.2%) (p = 0.78). CONCLUSION Our findings indicate that the MMP-7 A-181G polymorphism may not be correlated with susceptibility to breast cancer in our population.
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Affiliation(s)
- Kheirollah Yari
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ziba Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehrdad Payandeh
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zohreh Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Kesh K, Subramanian L, Ghosh N, Gupta V, Gupta A, Bhattacharya S, Mahapatra NR, Swarnakar S. Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB). J Biol Chem 2015; 290:14391-406. [PMID: 25847246 DOI: 10.1074/jbc.m114.630129] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Indexed: 01/27/2023] Open
Abstract
Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520). The GG genotype as compared with the AA genotype was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p = 0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis revealed that tobacco enhanced the risk for cancer more markedly in AG and GG carriers. Activity and expression of MMP7 were significantly higher in GG than in AA carriers. In support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine-induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the -181G than the -181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer.
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Affiliation(s)
- Kousik Kesh
- From the Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata 700032
| | - Lakshmi Subramanian
- the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, and
| | - Nillu Ghosh
- From the Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata 700032
| | - Vinayak Gupta
- the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, and
| | - Arnab Gupta
- the Saroj Gupta Cancer Center and Research Institute, Kolkata 700104, India
| | - Samir Bhattacharya
- the Saroj Gupta Cancer Center and Research Institute, Kolkata 700104, India
| | - Nitish R Mahapatra
- the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, and
| | - Snehasikta Swarnakar
- From the Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata 700032,
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Rahimi Z, Rahimi Z, Mohammadi F, Razazian N, Najafi F. Association of matrix metalloproteinase-7A-181G variants with the risk of multiple sclerosis. Per Med 2014; 11:727-733. [DOI: 10.2217/pme.14.42] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Aim: To investigate the influence of matrix metalloproteinase-7 (MMP-7) A-181G on the risk of multiple sclerosis (MS) and neurological disability. Patients & methods: The variants of MMP-7 were studied in 126 MS patients and 190 healthy controls. Results: The MMP-7 G allele and AG+GG genotype significantly increased the risk of MS in females (odds ratio: 1.59; p = 0.011) and patients with the age at disease onset of ≤19 years (odds ratio: 8.77; p = 0.038), respectively. Patients with clinical course of secondary progressive MS carriers of AG genotype had higher mean Expanded Disability Status Scale (4.9 ± 0.85; p = 0.01) compared with carriers of AA genotype (3.75 ± 0.41). Conclusion: The MMP-7 A-181G polymorphism might be associated with susceptibility to MS in females and individuals with the age at disease onset of ≤19 years and with neurological disability in secondary progressive MS.
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Affiliation(s)
- Ziba Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zohreh Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fatemeh Mohammadi
- Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Nazanin Razazian
- Department of Neuroscience, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farid Najafi
- Research Center for Environmental Determinants of Health, School of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem 2014; 5:355-376. [PMID: 25225603 PMCID: PMC4160529 DOI: 10.4331/wjbc.v5.i3.355] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
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Matrix metalloproteinase7 -181A/G polymorphism is associated with increased cancer risk among high-quality studies: Evidence from a meta-analysis. Clin Biochem 2013; 46:1649-54. [DOI: 10.1016/j.clinbiochem.2013.07.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Revised: 06/15/2013] [Accepted: 07/15/2013] [Indexed: 01/15/2023]
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Wu J, Guan X, Zhang K, Li YT, Bai P, Wu J. A/G polymorphism of matrix metalloproteinase 7 gene promoter region and cancer risk: A meta-analysis. Biomed Rep 2013; 1:792-796. [PMID: 24649030 DOI: 10.3892/br.2013.131] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Accepted: 07/08/2013] [Indexed: 01/10/2023] Open
Abstract
This meta-analysis was conducted to evaluate the effect of the matrix metalloproteinase 7 (MMP7)-181A/G polymorphism on cancer risk. Twenty-seven case-control studies were identified via a literature search through PubMed, Web of Science and China National Knowledge Infrastructure databases. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the association between MMP7-181A/G polymorphism and cancer risk. The 27 studies were further assessed according to Hardy-Weinberg equilibrium (HWE) and Hardy-Weinberg disequilibrium (HWD), with 24 case-control studies found to be under HWE. A significant association was observed between MMP7-181A/G polymorphism and increased cancer risk (cervical and other types of cancer) in Asian, but not in European populations.
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Affiliation(s)
- Jing Wu
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Xuan Guan
- School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
| | - Kui Zhang
- Laboratory of Molecular Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Ya-Ting Li
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Peng Bai
- Laboratory of Molecular Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Jin Wu
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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15
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Yang X, Liu Y, Yang Y, Li B. Update meta-analysis on MMP-7 −181A>G polymorphism and cancer risk: Evidence from 25 studies. Gene 2013; 521:252-8. [DOI: 10.1016/j.gene.2013.03.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2012] [Revised: 02/25/2013] [Accepted: 03/15/2013] [Indexed: 11/30/2022]
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16
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Ke P, Wu ZD, Wen HS, Ying MX, Long HC, Qing LG. Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk. Asian Pac J Cancer Prev 2013; 14:2269-72. [DOI: 10.7314/apjcp.2013.14.4.2269] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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17
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Mercer PF, Chambers RC. New tale for an old fox in IPF? Am J Physiol Lung Cell Mol Physiol 2013; 304:L466-8. [PMID: 23316070 DOI: 10.1152/ajplung.00286.2012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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18
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The relationship of metalloproteinase gene polymorphisms and lung cancer. J Surg Res 2013; 183:517-23. [PMID: 23465389 DOI: 10.1016/j.jss.2013.01.045] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Revised: 12/27/2012] [Accepted: 01/22/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND We analyzed the relationship between matrix metalloproteinase (MMP)-2, -7, and -13 gene expression and polymorphisms and disease susceptibility and prognosis in patients who had undergone surgery for non-small-cell lung cancers. MATERIALS AND METHODS The study group consisted of 132 patients who had undergone radical surgery for non-small-cell lung cancers. The control group consisted of 80 healthy volunteers. We isolated deoxyribonuclease samples for use in analyzing gene polymorphisms from pathology blocks for the patient group and from blood samples for the control group. We identified MMP gene polymorphisms with polymerase chain reaction and restriction fragment length polymorphisms. Results were compared with those of the control group to evaluate disease susceptibility, correlation with other clinical parameters, and with survival and prognosis by using appropriate statistical methods. RESULTS When we compared polymorphisms pertaining to MMP genes in healthy controls and lung tumor DNA, we observed a decrease in the MMP-2 (-735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes (P = 0.008, P = 0.047, and P = 0.047, respectively). For the MMP-7 (-181) polymorphism, the genotype did not differ significantly for disease susceptibility. Median overall survival time was 25.5 mo in the MMP-13 AA/AG genotypes and 9.3 mo in the GG genotype. CONCLUSIONS Decreases in the MMP-2 (-735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes increase the risk for lung cancer. Furthermore, the presence of the MMP-13 (A77G) polymorphism GG genotype is an unfavorable prognostic factor.
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Richards TJ, Park C, Chen Y, Gibson KF, Peter Di Y, Pardo A, Watkins SC, Choi AMK, Selman M, Pilewski J, Kaminski N, Zhang Y. Allele-specific transactivation of matrix metalloproteinase 7 by FOXA2 and correlation with plasma levels in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012; 302:L746-54. [PMID: 22268124 PMCID: PMC3331579 DOI: 10.1152/ajplung.00319.2011] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2011] [Accepted: 01/06/2012] [Indexed: 01/18/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a complex disease with poorly understood etiology. Previously, we reported upregulation of matrix metalloproteinase 7 (MMP7) in both lung and peripheral blood of IPF patients. Here we report evidence for genetic correlation of plasma levels and promoter polymorphisms (rs11568818 and rs11568819) of MMP7 in a well-characterized IPF cohort. Both the AA genotype of rs11568818 and the CT genotype of rs11568819 were found to be significantly associated with higher MMP7 plasma levels. These associations were observed only in IPF patients and not in healthy controls. The G-to-A transition of rs11568818 resulted in a novel binding site for the forkhead box A2 (FOXA2) transcription factor, a key regulator of embryonic lung development and proper function of the mature lung. In vitro, this transition led to increased sensitivity of the MMP7 promoter to FOXA2. In IPF lungs, FOXA2 was localized in the nucleus of epithelial cells that expressed MMP7 in the cytoplasm. These results suggest that increased sensitivity of the polymorphic MMP7 promoter to FOXA2 provides one of the genetic bases for the upregulation of MMP7 in IPF.
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Affiliation(s)
- Thomas J Richards
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, PA 15213, USA
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20
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Mogulkoc U, Coskunpinar E, Aynaci E, Cağlar E, Ortakoylu MG, Ozkan G, Oltulu YM, Eraltan IY. Is MMP-7 gene polymorphism a possible risk factor for chronic obstructive pulmonary disease in Turkish patients. Genet Test Mol Biomarkers 2012; 16:519-23. [PMID: 22417142 DOI: 10.1089/gtmb.2011.0271] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This study was performed to test the association between MMP-7 (rs155668818) and MMP-12 (rs56184183) polymorphisms in the MMP-7 gene and COPD risk and its severity in the Turkish population. MMP-7 and MMP-12 polymorphisms were genotyped in 85 patients with COPD and 73 healthy control subjects using real-time polymerase chain reaction analysis. There were significant differences in the distribution of MMP-7 genotypes but not in the frequencies of these alleles between COPD patients and controls (p=0.009, p=0.102, respectively). The MMP-7 AA genotype was found to be associated with an increased risk of COPD (p=0.004; odds ratio: 2.576; confidence interval: 1.297-5.119). The lowest values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC in patients with GG homozygosity were determined and these values were statistically significant compared to the control subjects (p<0.001, p<0.001, p<0.001). When the present study groups were analyzed for MMP-12 polymorphism, it was found that all the subjects had wild-type genotype for this polymorphism. These findings have suggested that MMP-7 polymorphism might be associated with the risk and progression of COPD in the Turkish population.
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Affiliation(s)
- Umit Mogulkoc
- Yedikule Chest Diseases and Chest Surgery, Training and Research Hospital, Istanbul, Turkey
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21
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Bavi PP, Bu R, Uddin S, Al-Kuraya KS. MMP7 Polymorphisms - A new tool in molecular pathology to understand esophageal cancer. Saudi J Gastroenterol 2011; 17:299-300. [PMID: 21912054 PMCID: PMC3178915 DOI: 10.4103/1319-3767.84479] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Prashant P. Bavi
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. E-mail:
| | - Rong Bu
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. E-mail:
| | - Shahab Uddin
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. E-mail:
| | - Khawla S. Al-Kuraya
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. E-mail:
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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; 17:301-306. [PMID: 21912055 PMCID: PMC3178916 DOI: 10.4103/1319-3767.84480] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2010] [Accepted: 02/11/2011] [Indexed: 01/20/2023] Open
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 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.
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Affiliation(s)
- Manzoor A. Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Kiran L. Sharma
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Showket A. Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
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Langers AM, Verspaget HW, Hommes DW, Sier CF. Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer. World J Gastrointest Oncol 2011; 3:79-98. [PMID: 21731908 PMCID: PMC3124635 DOI: 10.4251/wjgo.v3.i6.79] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Revised: 05/27/2011] [Accepted: 06/03/2011] [Indexed: 02/05/2023] Open
Abstract
Matrix metalloproteinases (MMPs) are implicated in cancer development and progression and are associated with prognosis. Single-nucleotide polymorphisms (SNPs) of MMPs, most frequently located in the promoter region of the genes, have been shown to influence cancer susceptibility and/or progression. SNPs of MMP-1, -2, -3, -7, -8, -9, -12, -13 and -21 and of the tissue inhibitor of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors. The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.
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Affiliation(s)
- Alexandra Mj Langers
- Alexandra MJ Langers, Hein W Verspaget, Daniel W Hommes, Cornelis FM Sier, Department of Gastroenterology and Hepatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
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24
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Fang WL, Liang WB, He H, Zhu Y, Li SL, Gao LB, Zhang L. Association of matrix metalloproteinases 1, 7, and 9 gene polymorphisms with genetic susceptibility to colorectal carcinoma in a Han Chinese population. DNA Cell Biol 2010; 29:657-61. [PMID: 20662554 DOI: 10.1089/dna.2010.1017] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Matrix metalloproteinases (MMPs) play an important role in colorectal cancer (CRC). Accumulated evidence suggests an association between MMP-1, MMP-7, and MMP-9 functional gene polymorphisms with several tumors. The aim of this study was to investigate the association of single-nucleotide polymorphism (SNP) at MMP-1 16071G/2G, MMP-7 181A/G, and MMP-9 279R/Q genes with CRC in the southwest Chinese Han population. The study used 237 CRC patients and 252 normal control matched by age and sex from Sichuan province in China. Samples were genotyped using both polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. We found significant differences in the genotype and allele frequency of MMP-9 279 R/Q between the case and control group. Individuals who carried MMP-9 279 R allele were more susceptible to CRC (odds ratio = 1.737, 95% confidence interval = 1.323-2.281, p < 0.001). Moreover, the RR genotype of MMP-9 279 R/Q was associated with an increased risk of CRC compared with the QQ genotype (odds ratio = 2.213, 95% confidence interval = 1.248-3.926, p = 0.006). However, there were no significant differences in the genotype and allele frequency of the MMP-1 16071G/2G and MMP-7 181 A/G between the case and control group, and the latter may be due to lower minor allele frequency. The MMP-9 279R/Q alleles and genotypes may be associated with the risk of CRC in Han Chinese.
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Affiliation(s)
- Wen-Liang Fang
- Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, PR China
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25
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Jaboin JJ, Hwang M, Lopater Z, Chen H, Ray GL, Perez C, Cai Q, Wills ML, Lu B. The matrix metalloproteinase-7 polymorphism rs10895304 is associated with increased recurrence risk in patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2010; 79:1330-5. [PMID: 20605361 DOI: 10.1016/j.ijrobp.2010.01.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2009] [Revised: 11/08/2009] [Accepted: 01/04/2010] [Indexed: 01/02/2023]
Abstract
PURPOSE To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer. METHODS AND MATERIALS Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years. Genotyping was performed using hybridization with custom-designed allele-specific probes. Three single nucleotide polymorphisms within the matrix metalloproteinase-7 gene were assessed with respect to age at diagnosis, margin status, extracapsular extension, lymph node involvement, recurrence-free survival, and overall survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer who underwent radical prostatectomy. RESULTS Rs10895304 was the sole significant polymorphism. The A/G genotype of rs10895304 had a statistically significant association with recurrence-free survival in postprostatectomy patients (p = 0.0061, log-rank test). The frequency of the risk-reducing genotype (A/A) was 74%, whereas that of the risk-enhancing genotypes (A/G and G/G) were 20% and 6%, respectively. Multivariable Cox regression analyses detected a significant association between rs10895304 and recurrences after adjustment for known prognostic factors. The G allele of this polymorphism was associated with increased risk of prostate cancer recurrence (adjusted hazards ratio, 3.375; 95% confidence interval 1.567-7.269; p < 0.001). The other assayed polymorphisms were not significant, and no correlations were made to other clinical variables. CONCLUSIONS The A/G genotype of rs10895304 is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer. Our data suggest that for this subset of patients, prostatectomy alone may not be adequate for local control. This is a novel and relevant marker that should be evaluated for improved risk stratification of patients who may be candidates for adjuvant radiation therapy to improve local control.
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Affiliation(s)
- Jerry J Jaboin
- Department of Radiation Oncology, Vanderbilt University, Nashville, TN, USA
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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. [PMID: 20360147 DOI: 10.1093/mutage/geq015] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Matrix metalloproteinase (MMP) 2, MMP7 and MMP9 are important members of the MMP family. Four polymorphisms in the promoter region of these MMPs, which are MMP2 -1306 C>T, MMP2 -735 C>T, MMP7 -181 A>G and MMP9 -1562 C>T, have been reported to be functional and may contribute to genetic susceptibility to cancers. However, the associations between these polymorphisms and cancer risk remain inconclusive due to conflicting results from different case-control studies. To better evaluate the role of these polymorphisms in cancer development, we conducted a meta-analysis that included 51 studies, with more than 40,000 subjects. The results showed that under dominant genetic model, MMP2 -1306 T was associated with lower susceptibility to lung cancer [odds ratio (OR) = 0.50, 95% confidence interval (CI) 0.43-0.59, P(heterogeneity) = 0.147, I(2) = 44.1%], head and neck cancer (OR = 0.53, 95% CI 0.41-0.69, P(heterogeneity) = 0.974, I(2) = 0.0%) and oesophageal cancer (OR = 0.67, 95% CI 0.55-0.80, P(heterogeneity) = 0.593, I(2) = 0.0%); MMP2-735T was associated with lower risk in lung cancer (OR = 0.65, 95%CI 0.53-0.79, P(heterogeneity) = 0.42, I(2) = 0.0%) and oesophageal cancer (OR = 0.84, 95% CI 0.70-0.99, P(heterogeneity) = 0.206, I(2) = 37.4%); MMP7 -181 AG and GG genotype carriers had an increased gastric cancer risk (OR = 1.90, 95% CI 1.43-2.51, P(heterogeneity) = 0.992, I(2) = 0.0%) and MMP9 -1562 C>T was not associated with cancer risk in the whole group analysis (OR = 0.99, 95% CI 0.91-1.08, P(heterogeneity) = 0.419, I(2) = 3.0%) and subgroup analyses. In all, our meta-analysis suggests that MMP2 -1306 C>T, MMP2 -735 C>T and MMP7 -181 A>G may play allele-specific roles in cancer development, while MMP9 -1562 C>T may not be a major risk factor for most cancer types. Large case-control studies should be performed to clarify the possible roles of these four polymorphisms in different kinds of cancer in more detail.
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Affiliation(s)
- Bo Peng
- State Key Laboratory of Genetic Engineering, Department of Genetics, Institute of Genetics, School of Life Science, Fudan University, Shanghai, People's Republic of China
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Beeghly-Fadiel A, Shu XO, Long J, Li C, Cai Q, Cai H, Gao YT, Zheng W. Genetic polymorphisms in the MMP-7 gene and breast cancer survival. Int J Cancer 2009; 124:208-14. [PMID: 18798254 PMCID: PMC2597698 DOI: 10.1002/ijc.23859] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression has been shown to be associated with tumor invasion, metastasis and survival for a variety of cancers. We systematically evaluated single nucleotide polymorphisms (SNPs) in MMP-7 in relation to breast cancer survival in a large follow-up study. Included were 1,079 breast cancer cases that were recruited from 1996 to 1998 and followed for a median of 7.1 years as part of the Shanghai Breast Cancer Study (SBCS). Eleven SNPs, including 2 known functional promoter SNPs, were analyzed using the Affymetrix Targeted Genotyping System. Associations with survival were evaluated by Cox proportional hazards regression and Kaplan-Meier functions. Statistically significant associations with disease-free and/or overall survival (OS) were found for 5 polymorphisms; these associations were explained primarily by 2 SNPs (rs11568818 and rs11225297) that were in high linkage disequilibrium (LD) with the others. Patients homozygous for the rs11568818 rare allele (G) had a significantly worse prognosis (OS HR: 6.7, 95% CI: 2.4-18.6) than patients homozygous for the common allele (A). Significantly improved survival was seen for patients with the rs11225297 T allele, and this association occurred in a dose-response manner; patients with AT (OS HR: 0.7, 95% CI: 0.5-0.9) and TT (OS HR: 0.3, 95% CI: 0.1-0.8) fared better than patients with AA (p-value for trend: 0.001). Thus, common MMP-7 genetic polymorphisms were found to be significant determinants of survival among Chinese women with breast cancer.
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Affiliation(s)
- Alicia Beeghly-Fadiel
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Xiao-ou Shu
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Jirong Long
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Chun Li
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Qiuyin Cai
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Hui Cai
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Wei Zheng
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
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Sugimoto M, Furuta T, Kodaira C, Nishino M, Yamade M, Ikuma M, Sugimura H, Hishida A. Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan. J Gastroenterol 2008; 43:751-761. [PMID: 18958543 DOI: 10.1007/s00535-008-2221-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2007] [Accepted: 05/17/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most macromolecules making up the extracellular matrix. MMPs are involved in not only the gastric mucosal inflammatory response but also the pathogenesis of Helicobacter pylori-associated diseases. In the renin-angiotensin system, chymase (CMA) is related to gastric carcinogenesis and angiogenesis in H. pylori-infected patients. We aimed to clarify the association of MMP-7-181 and CMA/B polymorphisms with susceptibility to gastric cancer and cancer progression in H. pylori-infected patients. METHODS We assessed the MMP-7-181 and CMA/B polymorphisms in H. pylori-positive patients with gastric cancer (n = 160), gastric ulcer (n = 157), duodenal ulcer (n = 121), and H. pylori-positive gastritis alone as controls (n = 156). RESULTS For gastric cancer risk, the age-and sex-adjusted odds ratio (OR) of the MMP-7-181 G allele carrier relative to the A/A genotype was significantly increased [OR, 2.32; 95% confidence interval (CI), 1.24-4.35], especially in patients with noncardia cancer (OR, 2.31; 95% CI, 1.22-4.36) and those with clinical stage III or IV cancer (OR, 3.66; 95% CI, 1.54-8.73). Carriage of the CMA/B A allele was significantly associated with gastric cancer development (OR, 1.73; 95% CI, 1.10-2.71). Simultaneous carriage of both the MMP-7-181 G allele and the CMA/B A allele dramatically increased the gastric cancer risk (OR, 8.18; 95% CI, 2.79-23.93). CONCLUSIONS In Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. MMP-7-181 and CMA/B genotyping tests might be useful tools for screening for individuals with higher gastric cancer risk.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Qiu W, Zhou G, Zhai Y, Zhang X, Xie W, Zhang H, Yang H, Zhi L, Yuan X, Zhang X, He F. No association of MMP-7, MMP-8, and MMP-21 polymorphisms with the risk of hepatocellular carcinoma in a Chinese population. Cancer Epidemiol Biomarkers Prev 2008; 17:2514-8. [PMID: 18768525 DOI: 10.1158/1055-9965.epi-08-0557] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Previous studies have suggested that the functional polymorphisms in the promoters of matrix metalloproteinases (MMP) genes were associated with the risk of cancers, but no study has ever explored these polymorphisms as risk factors for hepatocellular carcinoma. Recently, we firstly examined whether seven functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, and MMP-13 have any bearing on the risk of hepatocellular carcinoma, but we found none. In this study, we focused on an additional six MMP polymorphisms, including four functional polymorphisms in the promoters of MMP-7 (A-181G and C-153T) and MMP-8 (C-799T and A-381G), and two nonsynonymous polymorphisms in MMP-10 (A180G) and MMP-21 (C572T). With the polymorphism validation, we found that only MMP-7 A-181G, MMP-8 C-799T, and MMP-21 C572T were polymorphic. These three polymorphisms were then genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PRC-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk of hepatocellular carcinoma was observed with the three polymorphisms in the overall sample, hepatitis B virus carriers, and non-hepatitis B virus carriers after correction for multiple comparisons. Furthermore, when the analyses were stratified by age, sex, status of smoking and drinking, pack-years of smoking, and family history of hepatocellular carcinoma, there was also no significant association between these polymorphisms and hepatocellular carcinoma risk. Our findings suggest that the polymorphisms MMP-7 A-181G, MMP-8 C-799T, and MMP-21 C572T may not play a major role in mediating susceptibility to hepatocellular carcinoma.
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Affiliation(s)
- Wei Qiu
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
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Beeghly-Fadiel A, Long JR, Gao YT, Li C, Qu S, Cai Q, Zheng Y, Ruan ZX, Levy SE, Deming SL, Snoddy JR, Shu XO, Lu W, Zheng W. Common MMP-7 polymorphisms and breast cancer susceptibility: a multistage study of association and functionality. Cancer Res 2008; 68:6453-9. [PMID: 18648013 PMCID: PMC2718434 DOI: 10.1158/0008-5472.can-08-0636] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity against ECM and non-ECM components. Known to be vital for tumor invasion and metastasis, accumulating evidence also implicates MMP-7 in cancer development. Using data from the Shanghai Breast Cancer Study, we conducted a two-stage study to evaluate the association of MMP-7 single nucleotide polymorphisms (SNPs) with breast cancer risk. Additionally, associated SNPs were characterized by laboratory assays. In stage 1, 11 SNPs were genotyped among 1,079 incident cases and 1,082 community controls using an Affymetrix Genotyping System. Promising SNPs were selected for stage 2 evaluation and genotyped by TaqMan allelic discrimination assays in an independent set of 1,911 cases and 1,811 controls. Three SNPs were selected for stage 2 validation (rs880197, rs10895304, and rs12184413); one had highly consistent results between the two stages of the study. In combined analysis, homozygosity for the variant T allele for rs12184413 was associated with an odds ratio (OR) of 0.7 [95% confidence interval (95% CI), 0.6-0.9] compared with the common C allele. This effect was slightly more pronounced in postmenopausal women (OR, 0.6; 95% CI, 0.4-0.8) than in premenopausal women (OR, 0.8; 95% CI, 0.6-1.1). This SNP is located 3' of the MMP-7 gene, in an area enriched with CTCF binding sites. In silico analysis suggested a regulatory role for this region, and our in vitro assays showed an allelic difference in nuclear protein binding capacity. Results from our study suggest that common MMP-7 genetic polymorphisms may contribute to breast cancer susceptibility.
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Affiliation(s)
- Alicia Beeghly-Fadiel
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Ji-Rong Long
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Chun Li
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Shimian Qu
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Qiuyin Cai
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Ying Zheng
- Shanghai Center for Disease Prevention and Control, Shanghai, China
| | - Zhi-Xian Ruan
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Shawn E. Levy
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Sandra L. Deming
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Jay R. Snoddy
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Xiao-ou Shu
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Wei Lu
- Shanghai Center for Disease Prevention and Control, Shanghai, China
| | - Wei Zheng
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
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Singh H, Jain M, Mittal B. MMP-7 (-181A>G) promoter polymorphisms and risk for cervical cancer. Gynecol Oncol 2008; 110:71-75. [PMID: 18448157 DOI: 10.1016/j.ygyno.2008.03.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2008] [Revised: 03/14/2008] [Accepted: 03/19/2008] [Indexed: 01/30/2023]
Abstract
OBJECTIVES Matrix metalloproteinase (MMP-7) is a secreted matrilysin, which contributes to tumor progression through breakdown of basement membranes and angiogenesis. Therefore, we aimed to investigate the association of MMP-7 -181A>G gene polymorphism with risk of cervical cancer. METHODS In the present case control study, we enrolled a total of 150 cervical cancer patients confirmed by histopathology and 162 unrelated healthy individuals. Polymorphism for MMP-7 gene (-181A>G) was genotyped by polymerase chain reaction and restriction enzyme length polymorphism. RESULTS Frequency of MMP-7 -181GG genotype and -181G allele differed significantly between patients with cervical cancer (29.3%) and healthy individuals (19.4%) (P=0.041; OR(GG)=1.94 and P=0.048; OR(G)=1.94). Individuals with MMP-7 -181GG genotype were at higher risk of stage II of cervical cancer with borderline significance (P=0.05, OR=2.78; 95%CI: 0.89-8.69). However, interaction of MMP-7 -181AG and GG genotypes with tobacco usage did not modulate the cervical cancer risk significantly (OR 2.21, 95%CI=0.59-8.1 and OR 3.17, 95%CI=0.64-15.7). CONCLUSION Individuals with MMP-7 -181GG genotype were at significantly higher risk of cervical cancer.
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Affiliation(s)
- HariOm Singh
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India
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Woo M, Park K, Nam J, Kim JC. Clinical implications of matrix metalloproteinase-1, -3, -7, -9, -12, and plasminogen activator inhibitor-1 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol 2007; 22:1064-70. [PMID: 17608852 DOI: 10.1111/j.1440-1746.2006.04424.x] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Overexpression of matrix metalloproteinase (MMP)-1, -3, -7, -9, and plasminogen activator inhibitor-1 (PAI-1) are implicated in the invasion and metastasis of colorectal cancer, while MMP-12 provides a protective role against colorectal cancer. The promoter and exon polymorphisms of their genes, which are known to affect the transcription of these genes, were assessed to correlate with colorectal cancer susceptibility. METHODS MMP1, 3, 7, 9, 12 and PAI1 were assayed in 185 colorectal cancer patients and 304 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Respective genotypes and haplotypes were compared between the population groups and also between clinicopathological characteristics in the colorectal cancer patients. RESULTS The homozygous MMP1-1,607 dupG genotype was significantly more frequent in colorectal cancer patients than in healthy controls. The frequency of MMP1-1,607 dupG homozygotes was also greater in patients of less than or equal to 50 years of age, and in patients with 10 or more metastatic lymph nodes, compared with those of older age or with fewer lymph nodes. The frequency of MMP9-1,562 C homozygotes was significantly greater in colorectal cancer patients than in healthy controls. However, the genotype and allele frequencies of MMP3-1,171dupA, MMP7-181A > G, MMP12-82A > G, MMP9-90(CA)(14-27), and R279Q did not differ between the population groups or clinicopathological parameters. The MMP7-181A-MMP1-1,607dupG-MMP3-1,171A-MMP12-82A and MMP9-1,562C-90(CA)(20)+ 279Q haplotypes were significantly more frequent in colorectal cancer patients than in healthy controls. The genotype and allele frequencies of PAI1-675 G were similar between patients and healthy controls, but the frequency of PAI1-675 G homozygotes was significantly greater in patents over 50 years of age. CONCLUSIONS MMP1-1,607 dupG and MMP9-1,562 C homozygotes demonstrated an increased risk of colorectal cancer regardless of ethnic differences, whereas other MMP and PAI1 polymorphisms did not. Nevertheless, specific MMP haplotypes on 11q22.1-23.3 and 20q12-13 seem to be implicated in susceptibility to colorectal cancer.
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Affiliation(s)
- Mijung Woo
- Department of Biology, Graduate School SungShin Women's University, Seoul, Korea
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Lu Z, Cao Y, Wang Y, Zhang Q, Zhang X, Wang S, Li Y, Xie H, Jiao B, Zhang J. Polymorphisms in the matrix metalloproteinase-1, 3, and 9 promoters and susceptibility to adult astrocytoma in northern China. J Neurooncol 2007; 85:65-73. [PMID: 17502998 DOI: 10.1007/s11060-007-9392-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2007] [Accepted: 04/06/2007] [Indexed: 01/16/2023]
Abstract
The single nucleotide polymorphisms (SNPs) in the promoter region of matrix metalloproteinase (MMP) genes may influence tumor occurrence and progression via modifying mRNA transcription and protein expression. The study aims to explore the association of the SNPs in MMP-1, 3 and MMP-9 promoters with susceptibility to adult brain astrocytoma in northern China. Genotyping for the MMP-1 -1607 2G/1G, MMP-3 -1171 5A/6A, and MMP-9 -1562 C/T SNPs were performed by PCR-RFLP methods among 236 adult astrocytoma patients and 366 healthy controls. The results showed that the overall distribution of the MMP-1 allelotype and genotype among astrocytoma patients and healthy controls was significantly different (P = 0.002 and P < 0.001, respectively). Compared with the 2G/2G genotype, the 1G/1G genotype significantly decreased the risk of astrocytoma development (adjusted OR = 0.58, 95% CI = 0.42-0.79). The similar results were obtained when stratified by gender and age at tumor diagnosis (< or =45 or >45 years). The association between MMP-3 -1171 5A/6A or MMP-9 -1562 C/T SNPs and susceptibility to astrocytoma was not observed in this study. However, MMP-1 1G-MMP-3 6A haplotype significantly reduced the risk of astrocytoma development when using MMP-1 2G-MMP-3 6A haplotype as a reference (OR = 0.45, 95% CI = 0.29-0.67). The present study suggested that, the MMP-1 -1607 1G/1G genotype and MMP-1 1G-MMP-3 6A haplotype may play protective role in the development of adult astrocytoma in northern Chinese, whereas the MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms may not be independent factors to influence susceptibility to adult astrocytoma in this population.
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Affiliation(s)
- Zhongqiang Lu
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Hepinglu 215, 050000 Shijiazhuang, Hebei Province, China.
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Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma. BMC Cancer 2006; 6:270. [PMID: 17125518 PMCID: PMC1687194 DOI: 10.1186/1471-2407-6-270] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2006] [Accepted: 11/24/2006] [Indexed: 01/13/2023] Open
Abstract
Background Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. Methods Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. Results No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. Conclusion These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis.
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Lu Z, Wang Y, Zhang Q, Zhang X, Wang S, Xie H, Li Y, Jiao B, Zhang J. Association between the functional polymorphism in the matrix metalloproteinase-7 promoter and susceptibility to adult astrocytoma. Brain Res 2006; 1118:6-12. [PMID: 16956593 DOI: 10.1016/j.brainres.2006.08.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2006] [Revised: 08/02/2006] [Accepted: 08/04/2006] [Indexed: 12/11/2022]
Abstract
To study the association between the A to G transition at the -181-bp position in the promoter of matrix metalloproteinase-7 gene (MMP-7-181A/G) and susceptibility to adult astrocytoma, the MMP-7-181A/G polymorphism was genotyped by PCR-RFLP analysis among 221 adult astrocytoma patients and 366 healthy controls in a population of northern China. The result showed that the overall distribution of the MMP-7 genotypes among astrocytoma patients and healthy controls was significantly different (P<0.001). Compared with the A/A genotype, the G/G genotype significantly increased the risk to the development of astrocytoma (age and gender adjusted OR=2.77, 95% CI=1.27-6.02), while the MMP-7 A/G genotype only marginally increased the risk of developing this cancer (age and gender adjusted OR=1.66, 95% CI=0.99-2.84). Stratification analysis showed that the G/G genotype significantly increased the risk of astrocytoma only among male subjects (age adjusted OR=3.24, 95% CI=1.12-9.41) and individuals younger than 45 years (age and gender adjusted OR=3.16, 95% CI=1.09-9.16). When stratified by histological grades, a significant higher risk for developing grade II astrocytoma was observed among individuals harboring the A/G genotype (age and gender adjusted OR=2.06, 95% CI=1.05-4.05), while an about 3-fold elevation of risk to develop grades II, III, and IV astrocytomas was observed among individuals with the G/G genotype. The present result, for the first time, suggested that the MMP-7-181A/G polymorphism might be associated with the susceptibility to adult astrocytoma.
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Affiliation(s)
- Zhongqiang Lu
- Department of Neurosurgery, The Second Affiliated Hospital, Hebei Medical University, Hepinglu 205, Shijiazhuang, China.
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Kubben FJGM, Sier CFM, Meijer MJW, van den Berg M, van der Reijden JJ, Griffioen G, van de Velde CJH, Lamers CBHW, Verspaget HW. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. Br J Cancer 2006; 95:744-51. [PMID: 16940985 PMCID: PMC2360506 DOI: 10.1038/sj.bjc.6603307] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7−181A>G. In addition, the genotype distribution of MMP-7−181A>G was associated with Helicobacter pylori status (χ2 7.8, P=0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2303C>T correlated significantly with the WHO classification (χ2 5.9, P=0.03) and also strongly with tumour-related survival (log rank 11.74, P=0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2−1306C>T polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7−181A>G and TIMP-2303C>T polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7−181A>G and TIMP-2303C>T, may be helpful in identifying gastric cancer patients with a poor clinical outcome.
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Affiliation(s)
- F J G M Kubben
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - C F M Sier
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - M J W Meijer
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - M van den Berg
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - J J van der Reijden
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - G Griffioen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - C J H van de Velde
- Department of Oncologic Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - C B H W Lamers
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - H W Verspaget
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- E-mail:
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Li Y, Jin X, Kang S, Wang Y, Du H, Zhang J, Guo W, Wang N, Fang S. 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. [PMID: 16278009 DOI: 10.1016/j.ygyno.2005.09.058] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2005] [Revised: 09/01/2005] [Accepted: 09/27/2005] [Indexed: 11/22/2022]
Abstract
PURPOSE To investigate the association of single nucleotide polymorphisms (SNP) in the promoter region of the matrix metalloproteinases-1 -1607bp1G/2G, matrix metalloproteinases-3 -1171bp5A/6A, matrix metalloproteinases-7 A-181G and matrix metalloproteinases-9 C-1562T with susceptibility to ovarian cancer in a population of North China. EXPERIMENTAL DESIGN We analyzed four different functional promoter polymorphisms in the respective genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in a sample of patients with epithelium ovarian cancer and control women, all from North China. RESULTS No significant difference was detected between the patient and control groups in genotype and allelotype distribution of MMP-1, MMP-3, MMP-9 of the polymorphisms studied. However, the genotype and allelotype of the MMP-7 distribution in ovarian cancer patients were significantly different from that in healthy controls. The frequency of the -181G allele of MMP-7 in patients was significantly higher than that in healthy controls women (8.2% vs. 2.8%, P = 0.002). Compared to the A/A genotype, the genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to ovarian cancer, with adjusted odds ratio [OR] = 3.53 95% confidence interval [CI] [1.58 to 7.89]. CONCLUSIONS The study suggested that a possible association between the MMP-7 A/G polymorphism with susceptibility to epithelium ovarian cancer, but there is no support for an association of the selected MMP-1 1G/2G, MMP-3 5A/6A, and MMP-9 C/T polymorphisms with the risk for ovarian cancer.
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Affiliation(s)
- Yan Li
- Hebei Cancer Institute, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, Hebei Province, China.
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Shan K, Lian-Fu Z, Hui D, Wei G, Na W, Xia J, Yan L. Polymorphisms in the promoter regions of the matrix metalloproteinases-7, -9 and the risk of endometriosis and adenomyosis in China. Mol Hum Reprod 2006; 12:35-9. [PMID: 16455621 DOI: 10.1093/molehr/gal002] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Matrix metalloproteinases (MMPs) may contribute to the development of endometriosis. The aim of this study was to assess the effects of the polymorphisms in the promoters of MMP-7 (181A/G) and MMP-9 (1562C/T) on the risk of occurrence of endometriosis and adenomyosis. We genotyped 219 patients (143 women with endometriosis, 76 women with adenomyosis) and 160 control women in North China. There was a significant difference in frequency of the MMP-7 genotype between endometriosis and controls (P = 0.01) and also between adenomyosis and controls (P = 0.01). The frequency of the G allele in two groups of patients (7.3 and 7.9%) was significantly higher than in the controls (2.8%) (P = 0.01 and 0.01, respectively). Compared to the A/A genotype, the genotype with the -181G allele showed a significantly increased susceptibility to both diseases, with adjusted odds ratio of 2.62 [95% confidence interval (CI) = 1.17-5.87] for endometriosis and 3.14 (95% CI = 1.26-7.81) for adenomyosis. However, the overall genotype and allelotype distribution of the MMP-9 in the two case groups were not different from that of controls. We conclude that MMP-7-181A/G polymorphism has a potential to be a susceptibility factor for endometriosis and adenomyosis while MMP-9-1562C/T polymorphism may not provide a useful marker to predict susceptibility to endometriosis and adenomyosis, at least in women from North China.
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Affiliation(s)
- Kang Shan
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China
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Hellmig S, Ott S, Rosenstiel P, Robert Fölsch U, Hampe J, Schreiber S. Genetic variants in matrix metalloproteinase genes are associated with development of gastric ulcer in H. Pylori infection. Am J Gastroenterol 2006; 101:29-35. [PMID: 16405530 DOI: 10.1111/j.1572-0241.2005.00348.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most of the macromolecules making up the extracellular matrix. H. pylori infection increases the secretion of MMPs in the gastric mucosa leading to severe mucosal damage. The aim of this study was to investigate if genetic variants in MMPs involved in the inflammatory response to H. pylori could predispose patients with chronic H. pylori infection to develop gastric ulcer disease. METHODS A total of 599 H. pylori-infected patients undergoing gastroscopy were genotyped for 20 SNPs covering the MMP-1, -3, -7, and -9 genes by TaqMan technology. Haplotype and single marker analysis was conducted to assess associations with gastric ulcer disease. RESULTS Carriage of allele G of the functional promoter variant MMP-7-181 was significantly associated with gastric ulcer conferring a 1.6-fold increased risk (95% CI: 1.0-2.6, p = 0.037). In addition, carriage of allele A of a coding SNP in exon 6 of MMP-9 confers a 2.4-fold increased risk (95% CI: 1.0-2.6, p = 0.013) for gastric ulcer. CONCLUSION The level of association found in this study is in agreement with the nature of a complex genetic disease. Genetic variations in the MMP-7 and -9 gene may be part of a complex genetic risk profile to develop gastric ulcer in chronic H. pylori infection. Further studies are warranted to elucidate the pathophysiological role of these genes in ulcerogenesis.
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Affiliation(s)
- Stephan Hellmig
- Department of General Internal Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Germany
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Lugli E, Pinti M, Nasi M, Troiano L, Prada N, Mussini C, Borghi V, Esposito R, Cossarizza A. MMP-7 promoter polymorphisms do not influence CD4+ recovery and changes in plasma viral load during antiretroviral therapy for HIV-1 infection. Int J Immunogenet 2005; 32:269-71. [PMID: 16164692 DOI: 10.1111/j.1744-313x.2005.00523.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Matrix metalloproteinase-7 (MMP-7) generates soluble Fas Ligand (FasL), which is involved in the apoptotic loss of CD4+ T cells during HIV infection. We evaluated whether two polymorphisms in MMP-7 promoter could influence CD4+ recover in response to antiretroviral therapy, and found that these polymorphisms are ineffective.
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Affiliation(s)
- E Lugli
- Department of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia, 41100 Modena, Italy
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Zhang J, Jin X, Fang S, Wang R, Li Y, Wang N, Guo W, Wang Y, Wen D, Wei L, Dong Z, Kuang G. 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. [PMID: 15930031 DOI: 10.1093/carcin/bgi144] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
An A to G transition at the 181 base pair position upstream of the transcription initiation site of the matrix metalloproteinase-7 (MMP-7) gene (-181A/G) may modify the development and progression of some diseases via influencing the transcription activity of the promoter. To assess the effects of the functional single nucleotide polymorphism on cancer susceptibility and progression, the MMP-7 -181A/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis among 258 patients with esophageal squamous cell carcinoma (ESCC), 201 patients with gastric cardiac carcinoma (GCA), 243 patients with non-small cell lung carcinoma (NSCLC) and 350 healthy individuals without cancer. The result showed that the frequency of the -181G allele in ESCC, GCA and NSCLC patients was significantly higher than that in healthy controls (P = 0.019, 0.023 and 0.004, respectively). Compared with the A/A genotype, genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to all three tumors, with adjusted odds ratio of 1.83 (95% CI = 1.12-2.99) for ESCC, 1.96 (95% CI = 1.17-3.29) for GCA and 2.00 (95% CI = 1.23-3.24) for NSCLC. Stratification analysis showed that smoking did not significantly influence the association between the MMP-7-181A/G and GCA or NSCLC, while the -181G allele only significantly increased susceptibility to ESCC among smokers. In addition, association between the -181G allele and susceptibility to ESCC and GCA showed significance only among individuals with family history of upper gastrointestinal cancer. The correlation of the MMP-7-181A/G polymorphism with potential of lymphatic metastasis was not observed in all three tumors. The study suggested that, the MMP-7-181A/G polymorphism might be a candidate marker for predicting individuals who are at higher risk to certain tumors but might not be used to predict potential of lymphatic metastasis in ESCC, GCA and NSCLC.
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Affiliation(s)
- Jianhui Zhang
- Hebei Cancer Institute, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, Hebei Province, China.
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