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Wang BR, Ma HH, Chang CH, Liao CH, Chang WS, Mong MC, Yang YC, Gu J, Bau DT, Tsai CW. Contribution of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 to Upper Tract Urothelial Cancer Risk in Taiwan. Life (Basel) 2024; 14:801. [PMID: 39063556 PMCID: PMC11277778 DOI: 10.3390/life14070801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 06/20/2024] [Accepted: 06/22/2024] [Indexed: 07/28/2024] Open
Abstract
Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.
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Affiliation(s)
- Bo-Ren Wang
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
- Division of Urology, Department of Surgery, Taichung Armed Forces General Hospital, Taichung 41152, Taiwan
- National Defense Medical Center, Taipei 11490, Taiwan
| | - Hung-Huan Ma
- Division of Nephrology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Taichung 427003, Taiwan
| | - Chao-Hsiang Chang
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Urology, China Medical University Hospital, Taichung 404327, Taiwan
| | - Cheng-Hsi Liao
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
- Division of Urology, Department of Surgery, Taichung Armed Forces General Hospital, Taichung 41152, Taiwan
- National Defense Medical Center, Taipei 11490, Taiwan
| | - Wen-Shin Chang
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Mei-Chin Mong
- Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 413305, Taiwan
| | - Ya-Chen Yang
- Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 413305, Taiwan
| | - Jian Gu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Da-Tian Bau
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413305, Taiwan
| | - Chia-Wen Tsai
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Aziz MA, Jafrin S, Barek MA, Anonna SN, Islam MS. MMP-3 -1171 5A/6A promoter polymorphism and cancer susceptibility: an updated meta-analysis and trial sequential analysis. Future Oncol 2023; 19:1495-1512. [PMID: 37551683 DOI: 10.2217/fon-2022-1306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/09/2023] Open
Abstract
Purpose: Previous studies of MMP-3 -1171 5A/6A in cancers have produced inconclusive outcomes. This updated meta-analysis was performed to clarify the link between this variant and cancer. Methods: Databases including PubMed, Google Scholar, EMBASE and Cochrane were searched for data collection. The associations were calculated by odds ratios with 95% CIs. Results: 63 eligible studies with 14,252 cases and 15,176 controls were included. The codominant 2, codominant 3, dominant, recessive and allele models were found to be significantly associated with 1.28-, 1.13-, 1.13-, 1.19- and 1.13-fold enhanced overall risk of cancer, respectively. Stratification analysis revealed a 1.28-times enhanced risk of esophageal cancer (codominant 1), 1.29- and 1.26-fold (codominant 3) and 1.18- and 1.28-fold (recessive model) enhanced risk in colorectal and gastrointestinal cancers, respectively, 1.30-, 1.35- and 1.22-times in codominant model 1, dominant and allele models for breast cancer, 1.56-fold (codominant 2) for gynecological cancer and 2.40-times in codominant model 2 for hepatocellular cancer. Conclusion: This meta-analysis suggests a significant association between the MMP-3 -1171 5A/6A variant and cancer. This meta-analysis was registered at INPLASY (registration number: INPLASY202280049).
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Affiliation(s)
- Md Abdul Aziz
- Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Chittagong, Bangladesh
- Laboratory of Pharmacogenomics & Molecular Biology, Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Bangladesh
| | - Sarah Jafrin
- Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Chittagong, Bangladesh
- Laboratory of Pharmacogenomics & Molecular Biology, Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Bangladesh
| | - Md Abdul Barek
- Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Chittagong, Bangladesh
- Laboratory of Pharmacogenomics & Molecular Biology, Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Bangladesh
| | - Shamima Nasrin Anonna
- Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Chittagong, Bangladesh
- Laboratory of Pharmacogenomics & Molecular Biology, Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Bangladesh
| | - Mohammad Safiqul Islam
- Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Chittagong, Bangladesh
- Laboratory of Pharmacogenomics & Molecular Biology, Department of Pharmacy, Noakhali Science & Technology University, Sonapur, 3814, Noakhali, Bangladesh
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Barakat LA, Elsergany AR, Ghattas MH, Mahsoub N, Bondok RM. Relationship between interferon-induced transmembrane protein 3 and matrix metalloproteinase-9 gene polymorphisms in patients with hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2023; 47:102110. [PMID: 36914067 DOI: 10.1016/j.clinre.2023.102110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/08/2023] [Accepted: 03/08/2023] [Indexed: 03/15/2023]
Abstract
BACKGROUND Hepatocellular carcinoma originates from hepatocytes as a result of the effects of numerous genetic variations. Interferon-Induced Transmembrane protein 3 (IFITM3) is involved in the processes of cellular differentiation, apoptosis, cell adhesion, and immune cell regulation. Matrix Metalloproteinase-9 (MMP-9) are zinc dependent endopeptidases that cleave extracellular matrix contents and play an important role in the progression of cancer. OBJECTIVE The study aimed to outline the key molecular biology progression in hepatocellular carcinoma and the relationship between hepatocellular cancer and genetic polymorphisms of IFITM3 and MMP-9. METHODS In total 200 patients with hepatocellular carcinoma patients (n=100) and a control group with Hepatitis C virus (n=100) which collected randomly from the EL-Mansoura oncology center during the interval between June 2020 and October 2021. The expression of MMP-9 and the IFITM3 SNP was investigated. MMP-9 gene polymorphisms were estimated by using PCR-RFLP and IFITM3 gene was detected using DNA sequencing, ELISA was used to measure protein levels of MMP-9 and IFITM3. RESULTS The T allele of MMP-9 was more frequent among patients (n=121) than control subjects (n=71). The C allele of IFITM3 was more frequent among patients (n=112) than control subjects (n=83), polymorphisms of the genes linked to a high risk of disease development, patients of MMP-9 (TT genotype), odd ratio (OR) = 2.63, IFITM3 (CC genotype), OR= 2.43. CONCLUSIONS We found that the genetic polymorphisms of MMP-9 and IFITM3 are related to the occurrence and development of hepatocellular carcinoma. This study might be utilized in clinical diagnosis and therapy and to provide a baseline for prevention.
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Affiliation(s)
- Lamiaa A Barakat
- Department of Biochemistry, Faculty of Science, Port-Said University, Egypt.
| | - Alyaa R Elsergany
- Internal Medicine Department , Oncology Center, Faculty of Medicine, Mansoura University, Egypt
| | - Maivel H Ghattas
- Department of Medical Biochemistry, Faculty of Medicine, Port-Said University, Egypt
| | - Nancy Mahsoub
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt
| | - Rania M Bondok
- Department of Biochemistry, Faculty of Science, Port-Said University, Egypt
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4
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A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma. Nat Commun 2022; 13:4594. [PMID: 35933472 PMCID: PMC9357016 DOI: 10.1038/s41467-022-32283-3] [Citation(s) in RCA: 170] [Impact Index Per Article: 56.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 07/23/2022] [Indexed: 11/22/2022] Open
Abstract
Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generate a single-cell atlas of the multicellular ecosystem of HCC from four tissue sites. We show the enrichment of central memory T cells (TCM) in the early tertiary lymphoid structures (E-TLSs) in HCC and assess the relationships between chronic HBV/HCV infection and T cell infiltration and exhaustion. We find the MMP9+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and PPARγ to be the pivotal transcription factor driving their differentiation. We also characterize the heterogeneous subpopulations of malignant hepatocytes and their multifaceted functions in shaping the immune microenvironment of HCC. Finally, we identify seven microenvironment-based subtypes that can predict prognosis of HCC patients. Collectively, this large-scale atlas deepens our understanding of the HCC microenvironment, which might facilitate the development of new immune therapy strategies for this malignancy. The immune cell constituents and localisation within human hepatocellular carcinoma is not fully understood. Here the authors use single cell RNA sequencing of HCC from four different tissue sites and show differences between primary and metastatic tumours, tumour associated macrophages and immune cell populations.
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5
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MMP-2 and MMP-9 gene polymorphisms and risk of head and neck carcinomas. REV ROMANA MED LAB 2022. [DOI: 10.2478/rrlm-2022-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
Background: Head and neck carcinomas (HNC) account for a majority of ear, nose and throat tumours. They account for 6.3% of all incident malignancies and 6.2 % of all deaths from cancer in Romania in 2020, the fifth most common cancer in this Eastern Europe country. Aim of the study: The aim of our study was to investigate the association between two MMP-2 and MMP-9 promoter gene polymorphisms and head and neck cancer.
Methods. We enrolled 142 subjects, 65 cancer patients, and 77 control subjects and tested them for MMP-2 -735 C/T and MMP-9 -1562 C/T polymorphisms by PCR-RFLP.
Results. Comparison between cancer patients and controls demonstrated the presence of MMP-2 -735 C/T and MMP-9 -1562 C/T in head and neck malignant tumours, with OR = 2.206 (95% CI 1.058-4.599, P = 0.03) for MMP-2 and OR = 2.748 (95% C.I. 1.262-5.981, P=0.009) for MMP-9 gene polymorphism. This means that the presence of T allele could be a risk factor for head and neck cancer development. The analysis included a stratification of studied groups by age and gender.
Conclusions. Both genotypes were associated with a significant risk for head and neck carcinomas in case of the presence of the T allele. MMP-2 -735 C/T (rs2285053) and MMP-9 -1562 C/T (rs3918242) gene polymorphism could be an important genetic marker for head and neck cancer susceptibility. This finding could be useful for genetic screening in head and neck carcinomas.
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Elshimi E, Sakr MASM, Morad WS, Mohammad L. Optimizing the Diagnostic Role of Alpha-Fetoprotein and Abdominal Ultrasound by Adding Overexpressed Blood mRNA Matrix Metalloproteinase-12 for Diagnosis of HCV-Related Hepatocellular Carcinoma. Gastrointest Tumors 2019; 5:100-108. [PMID: 30976581 DOI: 10.1159/000495838] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 11/22/2018] [Indexed: 12/19/2022] Open
Abstract
Background and Aims Matrix metalloproteinase-12 (MMP-12) is involved in tumor invasiveness and metastasis and significantly overexpressed in hepatocellular carcinoma (HCC) tissues. We aimed to investigate the diagnostic and prognostic value of blood mRNA MMP-12 overexpression in patients with HCC. Patients and Methods From January 2017 to June 2017, 100 patients with HCC (HCV-related cirrhosis) and 100 patients with HCV-related cirrhosis (without HCC) were included in this study. All patients were subjected to triphasic CT abdomen when indicated, liver profile, alpha-fetoprotein (AFP), and molecular characterization of metalloproteinase-12 expression. Results There were no statistically significant differences between both groups regarding CBC parameters and liver profile (p value > 0.05). There was a statistically significant difference between patients with and without HCC regarding blood mRNA MMP-12 overexpression (p value < 0.01), blood mRNA MMP-12, and/or AFP (sensitivity 84.0%, specificity 60.0%, PPV 51.2%, and NPP 88.2%). The accuracy of mRNA MMP-12 and/or AFP in detection of HCC was 68.0%. Conclusion Blood mRNA MMP-12 has a good sensitivity and a bad specificity but is accurate in HCC diagnosis. Adding blood mRNA MMP-12 to AFP optimizes the current screening program to improve early diagnosis of HCC and hence better prognosis.
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Affiliation(s)
- Esam Elshimi
- Hepatology Department, National Liver Institute, Menoufia University, Shebin Al-Kom, Egypt
| | | | - Wesam Saber Morad
- Community Department, National Liver Institute, Menoufia University, Shebin Al-Kom, Egypt
| | - Lobna Mohammad
- Genetic Engineering Institute, Sadat University, Sadat, Egypt
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7
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A Matrix Metalloproteinase-1 Polymorphism, MMP1-1607 (1G>2G), Is Associated with Increased Cancer Risk: A Meta-Analysis Including 21,327 Patients. DISEASE MARKERS 2018; 2018:7565834. [PMID: 30627228 PMCID: PMC6305015 DOI: 10.1155/2018/7565834] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/23/2018] [Accepted: 09/26/2018] [Indexed: 12/14/2022]
Abstract
Although the matrix metalloproteinase-1 (MMP1) polymorphism MMP1-1607 (1G>2G) has been associated with susceptibility to various cancers, these findings are controversial. Therefore, we conducted this meta-analysis to explore the association between MMP1-1607 (1G>2G) and cancer risk. A systematic search of literature through PubMed, Embase, ISI Web of Knowledge, and Google Scholar yielded 77 articles with 21,327 cancer patients and 23,245 controls. The association between the MMP1-1607 (1G>2G) polymorphism and cancer risks was detected in an allele model (2G vs. 1G, overall risk [OR]: 1.174, 95% confidence interval [CI]: 1.107-1.244), a dominant model (2G2G/1G2G vs. 1G1G OR, OR: 1.192, 95% CI: 1.090-1.303), and a recessive model (2G2G vs. 1G2G/1G1G, OR: 1.231, 95% CI: 1.141-1.329). In subgroup analysis, these associations were detected in both Asians and Caucasians. After stratification by cancer types, associations were found in lung, colorectal, nervous system, renal, bladder, and nasopharyngeal cancers. This meta-analysis revealed that MMP1-1607 (1G>2G) polymorphism was significantly associated with elevated risk of cancers.
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8
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Hu C, Weng F, Li L, Dai W, Yan J, Peng L, Zhou R. Association between MMP-9 -1562 C/T polymorphism and susceptibility to digestive cancers: A meta-analysis. Gene 2018; 673:88-94. [PMID: 29890308 DOI: 10.1016/j.gene.2018.06.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 04/21/2018] [Accepted: 06/08/2018] [Indexed: 11/18/2022]
Abstract
PURPOSE Matrix metalloproteinases (MMPs) play important roles in tumorigenesis. The variant in MMP-9 -1562 C/T (single nucleotide polymorphisms labeled rs3918242) has been extensively evaluated as predisposing factors to digestive cancers susceptibility. However, most of these studies only contained a small number of subjects and they showed conflicting results. Therefore, to elucidate these associations, we carried out a large-scale meta-analysis to provide this accurately comprehensive synopsis of case-control studies. METHODS A comprehensive literature search was conducted in EMBASE, OVID, Medline, China National Knowledge Internet and Wanfang for relevant data published between Jan 2000 and Mar 2018. Overall and stratified analyses based on the cancer types, ethnicity and source of control were carried out. Odds ratios (ORs) correspondent to 95% confidence intervals (95% CIs) were calculated to evaluate the genetic correlation between the variant and digestive cancer susceptibility. Review Manager 5.2 and Stata 12.0 were used for statistical analysis. RESULTS Twenty studies containing 3201 digestive cancer patients and 4301 matched-controls were screened out. The overall results suggested that MMP-9 -1562 C/T polymorphism increased the susceptibility to digestive cancers under homozygote and recessive models (homozygote, OR = 1.35, 95% CI 1.00-1.82, P = 0.05; recessive, OR = 1.42, 95% CI 1.07-1.88, P = 0.02). Furthermore, in the subgroup analysis based on the source of control, similar conclusions were obtained in the population-based control subgroup (homozygote, OR = 1.63, 95% CI 1.16-2.27, P = 0.004; recessive, OR = 1.67, 95% CI 1.22-2.28, P = 0.001), but not in the hospital-based control. In subgroup analyses based on cancer types and ethnicity, no association was observed. CONCLUSIONS Our meta-analysis suggested that MMP-9 -1562 C/T polymorphism might be related to the digestive cancer susceptibility. Evidence with adequate sample size is needed.
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Affiliation(s)
- Chaoliang Hu
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Fangzhong Weng
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Lin Li
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Wei Dai
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Jun Yan
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Liqing Peng
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Ruixiang Zhou
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China.
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9
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Yu L, Zhang X, Zhai Y, Zhang H, Yue W, Zhang X, Wang Z, Zhou H, Zhou G, Gong F. Association of polymorphisms in the heparanase gene (HPSE) with hepatocellular carcinoma in Chinese populations. Genet Mol Biol 2017; 40:743-750. [PMID: 28981558 PMCID: PMC5738625 DOI: 10.1590/1678-4685-gmb-2014-0338] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 05/11/2015] [Indexed: 01/08/2023] Open
Abstract
Heparanase activity is involved in cancer growth and development in humans and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be associated with tumors. In this study, we investigated whether SNPs in HPSE were a risk factor for hepatocellular carcinoma (HCC) by undertaking a comprehensive haplotype-tagging, case-control study. For this, six haplotype-tagging SNPs (htSNPs) in HPSE were genotyped in 400 HCC patients and 480 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A log-additive model revealed significant correlations between the HPSE polymorphisms rs12331678 and rs12503843 and the risk of HCC in the overall samples (p = 0.0046 and p = 0.0055). When the analysis was stratified based on hepatitis B virus (HBV) carrier status, significant interactions between rs12331678 and rs12503843 and HBV were observed. Conditional logistic regression analysis for the independent effect of one significant SNP suggested that rs12331678 or rs12503843 contributed an independent effect to the significant association with the risk of HCC, respectively. Our findings suggest that the SNPs rs12331678 and rs12503843 are HCC risk factors, although the potential functional roles of these two SNPs remain to be fully elucidated.
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Affiliation(s)
- Lixia Yu
- Institute of Transfusion Medicine, Beijing, P. R. China
| | - Xiaoai Zhang
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Yun Zhai
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Hongxing Zhang
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Wei Yue
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Xiumei Zhang
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Zhifu Wang
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Hong Zhou
- Institute of Transfusion Medicine, Beijing, P. R. China
| | - Gangqiao Zhou
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China
| | - Feng Gong
- Institute of Transfusion Medicine, Beijing, P. R. China
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10
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Bao Z, Lu L, Liu X, Guo B, Zhai Y, Li Y, Wang Y, Xie B, Ren Q, Cao P, Han Y, Jia W, Chen M, Liang X, Wang X, Zeng YX, He F, Zhang H, Cui Y, Zhou G. Association between the functional polymorphism Ile31Phe in the AURKA gene and susceptibility of hepatocellular carcinoma in chronic hepatitis B virus carriers. Oncotarget 2017; 8:54904-54912. [PMID: 28903390 PMCID: PMC5589629 DOI: 10.18632/oncotarget.18613] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 05/22/2017] [Indexed: 11/25/2022] Open
Abstract
Aurora kinase A (AURKA) is a serine threonine kinase which affects chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. Two functional nonsynonymous polymorphisms of the AURKA gene (Ile31Phe and Val57Ile) have been reported recently. We analyzed the association between the two polymorphisms and risk of the occurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Guangxi population consisting of 348 patients with HCC and 359 control subjects, and then validated the significant association in the Guangdong population consisting of 440 cases and 456 controls. All of the participants were of Chinese origin and HBV carriers. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay or Sequenom MassARRAY iPLEX platform. In the Guangxi population, carriers of the AURKA 31Phe allele (Ile/Phe + Phe/Phe) were significantly associated with decreased susceptibility to HBV-related HCC when compared with noncarriers (Ile/Ile) (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.46-0.86, P = 3.4 × 10-3). On the contrary, no significant association was found between Val57Ile and HBV-related HCC occurrence. The association of Ile31Phe with HBV-related HCC occurrence was confirmed in the Guangdong population (OR = 0.64, 95% CI = 0.49-0.83, P = 8.0 × 10-4). The pooled analysis gave a joint P value of 5.5 × 10-6 (joint OR = 0.63, 95% CI = 0.52-0.77). Our findings suggest that AURKA Ile31Phe may play a role in mediating the susceptibility to HBV-related HCC among Chinese.
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Affiliation(s)
- Zhiyu Bao
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,Guangxi Medical University, Nanning, China.,Affiliated Hospital of Jining Medical University, Jining, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Lei Lu
- Department of Surgical Oncology, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Jindu Hospital, Nanjing, China
| | - Xinyi Liu
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Bingqian Guo
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Yun Zhai
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Yuanfeng Li
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Yahui Wang
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Bobo Xie
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Qian Ren
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Pengbo Cao
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Yuqing Han
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Weihua Jia
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Minshan Chen
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | | | - Xuan Wang
- Department of Surgical Oncology, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Jindu Hospital, Nanjing, China
| | - Yi-Xin Zeng
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Fuchu He
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Hongxing Zhang
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China
| | - Ying Cui
- Guangxi Medical University, Nanning, China
| | - Gangqiao Zhou
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.,National Engineering Research Center for Protein Drugs, Beijing, China.,National Center for Protein Sciences Beijing, Beijing, China.,Anhui Medical University, Hefei, Anhui, China
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11
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Lai YL, Gong CL, Fu CK, Yueh TC, Tsai CW, Chang WS, Hsiao CL, Yen ST, Li HT, Jeng LB, Wang SC, Bau DAT. The Contribution of Matrix Metalloproteinase-1 Genotypes to Hepatocellular Carcinoma Susceptibility in Taiwan. Cancer Genomics Proteomics 2017; 14:119-125. [PMID: 28387651 DOI: 10.21873/cgp.20024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 02/28/2017] [Accepted: 02/28/2017] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND/AIM Metalloproteinases (MMPs) are a family of proteases which have been shown to be overexpressed in various types of cancers. However, the contribution of MMP1 genotype to hepatocellular carcinoma (HCC) has not been well studied. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of HCC in Taiwan, where HCC incidence is relatively high in the world. MATERIALS AND METHODS In this case-control study, MMP1 genotype and its interaction with consumption of cigarettes and alcohol in determining HCC risk was investigated among 298 HCC patients and 889 age- and gender-matched healthy controls. RESULTS The percentages of ever smokers and ever alcohol drinkers were much higher in the case group than in the control group. The percentages of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype were 37.2%, 38.3% and 24.5% in the HCC group and 34.8%, 44.0% and 21.2% in the control group, respectively (p for trend=0.2048). The allelic frequency distribution analysis showed the variant 1G allele of MMP1 promoter 1607 conferred similar HCC susceptibility as the wild-type 2G allele (odds ratio (OR)=1.01, 95% confidence interval (CI)=0.84-1.22, p=0.8735). As for the gene-lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G allele on the risk of HCC among non-smokers, but not non-smokers, even alcohol drinkers or non-drinkers. CONCLUSION The 1G allele of MMP1 promoter 1607 may have a protective effect on HCC risk for non-smokers in Taiwan and further validations are needed in other population groups.
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Affiliation(s)
- Yi-Liang Lai
- Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C
| | - Chi-Li Gong
- Department of Physiology, China Medical University, Taichung, Taiwan, R.O.C
| | - Chun-Kai Fu
- Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C
| | - Te-Cheng Yueh
- Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C
| | - Chia-Wen Tsai
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C
| | - Wen-Shin Chang
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C
| | - Chieh-Lun Hsiao
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C
| | - Shiou-Ting Yen
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C
| | - Hsin-Ting Li
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C
| | - Long-Bin Jeng
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C
| | - Shou-Cheng Wang
- Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C. .,Natiosnal Defense Medical Center, Taipei, Taiwan, R.O.C
| | - DA-Tian Bau
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C. .,Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.,Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C
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12
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Haque S, Akhter N, Lohani M, Ali A, Mandal RK. Matrix metalloproteinase-2 -1306 C>T gene polymorphism is associated with reduced risk of cancer: a meta-analysis. Asian Pac J Cancer Prev 2015; 16:889-96. [PMID: 25735378 DOI: 10.7314/apjcp.2015.16.3.889] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.
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Affiliation(s)
- Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia E-mail :
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13
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Kim SK, Kang SW, Park HJ, Ban JY, Oh CH, Chung JH, Oh IH, Cho KB, Park MS. Meta-analysis of association of the matrix metalloproteinase 2 (-735 C/T) polymorphism with cancer risk. Int J Clin Exp Med 2015; 8:17096-17101. [PMID: 26770302 PMCID: PMC4694202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 10/10/2015] [Indexed: 06/05/2023]
Abstract
The association between matrix metalloproteinase 2 (MMP2) gene polymorphisms and cancer risk has been investigated in many published studies; however, the currently available results are inconclusive. Therefore, we performed a meta-analysis to provide conclusive evidence for an association between the MMP2 polymorphism (-735 C/T) and cancer risk. Sixteen case-control studies with 11792 individuals were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Overall, the MMP2 polymorphism (-735 C/T) was not associated with cancer risk in any of the models. However, the subgroup analysis revealed that dominant model (C/T+T/T vs. C/C: OR=1.24, 95% CI=1.01-1.53) and codominant 1 model (C/T vs. C/C: OR=1.30, 95% CI=1.05-1.62) were significantly associated with cancer risk in the Caucasian population. In conclusion, our meta-analysis indicated that the MMP2 polymorphism (-735 C/T) might be genetic risk factor for the carcinogenesis in Caucasians. However, more studies with a larger sample size are needed to provide more precise evidence.
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Affiliation(s)
- Su Kang Kim
- Kohwang Medical Research Institute, School of Medicine, Kyung Hee UniversitySeoul, Republic of Korea
| | - Sang Wook Kang
- Kohwang Medical Research Institute, School of Medicine, Kyung Hee UniversitySeoul, Republic of Korea
| | - Hae Jeong Park
- Kohwang Medical Research Institute, School of Medicine, Kyung Hee UniversitySeoul, Republic of Korea
| | - Ju Yeon Ban
- Department of Medical Laser, Dankook UniversityGraduate School, Cheonan, Republic of Korea
| | - Chung-Hun Oh
- Department of Medical Laser, Dankook UniversityGraduate School, Cheonan, Republic of Korea
| | - Joo-Ho Chung
- Kohwang Medical Research Institute, School of Medicine, Kyung Hee UniversitySeoul, Republic of Korea
| | - In-Hwan Oh
- Department of Preventive Medicine, School of Medicine, Kyung Hee UniversitySeoul, Republic of Korea
| | - Kyu Bong Cho
- Department of Biomedical Laboratory Science, College of Health Sciences, Shinhan UniversityGyeonggi, Republic of Korea
| | - Min-Su Park
- Department of Surgery, School of Medicine, Kyung Hee UniversitySeoul, Republic of Korea
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14
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Liu L, Sun J, Li G, Gu B, Wang X, Chi H, Guo F. Association between MMP-12-82A/G polymorphism and cancer risk: a meta-analysis. Int J Clin Exp Med 2015; 8:11896-11904. [PMID: 26550102 PMCID: PMC4612787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 08/08/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Numerous studies have focused on the association between MMP-12-82A>G polymorphism and cancer risk, but produced inconsistent results. Therefore, we performed a meta-analysis of case-control study to evaluate the association of MMP-12-82A>G polymorphism and cancer risk. METHODS A systematic literature search was conducted among PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI) and Wangfang databases updated on May 1st, 2015. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between this polymorphism and cancer risk. RESULTS A total of seventeen case-control studies with 7,450 cases and 7,348 controls were identified and analyzed. Overall, there was no statistically significant association between MMP-12-82A>G polymorphism and increased risk of cancer under all genetic models. Subgroup analysis by ethnicity observed that there is no strong relationship between MMP-12-82A>G polymorphism and cancer risk among Asian and European populations. Furthermore, stratified analysis based on the source of control revealed no statistically significant association between MMP-12-82A>G polymorphism and cancer risk either in hospital-based or population-based studies. However, when we stratified analysis based on cancer type, significant association was found in ovarian cancer, but not in other types of cancer. CONCLUSION This meta-analysis suggests that MMP-12-82A>G polymorphism is not significantly associated with overall cancer risk. However, MMP-12-82A>G polymorphism may increase the susceptibility to ovarian cancer.
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Affiliation(s)
- Luliang Liu
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
| | - Jinhuan Sun
- Department of Periodontology, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
| | - Guolin Li
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
| | - Boyu Gu
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
| | - Xiaolong Wang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
| | - Huirong Chi
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
| | - Fulin Guo
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin, Heilongjiang, China
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15
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Chen SS, Song J, Tu XY, Zhao JH, Ye XQ. The association between MMP-12 82 A/G polymorphism and susceptibility to various malignant tumors: a meta-analysis. Int J Clin Exp Med 2015; 8:10845-10854. [PMID: 26379878 PMCID: PMC4565261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 07/09/2015] [Indexed: 06/05/2023]
Abstract
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for degrading essentially all components of the extracellular matrix (ECM). Accumulating evidence suggests that MMPs might play a critical role in growth, invasion, and metastasis of malignant tumors. A single nucleotide polymorphism (SNP) in the promoter region of MMP-12, MMP-12 82 A/G (rs2276109), has been recognized to play a critical role in regulating the expression of MMP-12, however, its correlation with tumor susceptibility remains controversial. To address this issue, we performed meta-analysis to investigate the association MMP-12 82 A/G polymorphism and susceptibility of nine malignant tumors from 11 studies, including 6153 cancer patients and 6838 controls. Two reviewers independently screened studies for eligibility and extracted data for included studies. While overall no evident association between MMP-12 82 A/G and tumor susceptibility was observed, subgroup analysis revealed a specific role of G allele in increasing the susceptibility for epithelial ovarian carcinoma (EOC) using the allele model (fixed effects OR = 2.45, 95% CI = 1.46-4.10, P = 0.001) and the dominant model (fixed effects OR = 2.52, 95% CI = 1.49-4.24, P = 0.001). We thus suggest that G allele of MMP-12 82 A/G polymorphism is a genetic risk factor for EOC.
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Affiliation(s)
- Sheng-Song Chen
- Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China
| | - Juan Song
- Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China
| | - Xiao-Yun Tu
- Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China
| | - Ji-Hua Zhao
- Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China
| | - Xiao-Qun Ye
- Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China
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16
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Lu L, Sun Y, Li Y, Wan P. The polymorphism MMP1 -1607 (1G>2G) is associated with a significantly increased risk of cancers from a meta-analysis. Tumour Biol 2014; 36:1685-93. [PMID: 25391421 DOI: 10.1007/s13277-014-2769-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Accepted: 10/23/2014] [Indexed: 12/16/2022] Open
Abstract
Growing evidences show that matrix metalloproteinase 1 (MMP1) plays important roles in tumorigenesis and cancer metastasis. MMP1 -1607 1G>2G is a single nucleotide polymorphism in the promoter region of MMP1 and affects MMP1 production. Analysis of previous studies on the association of -1607 1G>2G polymorphism with different cancer types remained to be illustrated. To further assess the effect of -1607 1G>2G polymorphism on cancer risk, we performed this meta-analyses, up to September 8, 2014, of 10,640 cases and 10,915 controls from 42 published case-control designed studies. Statistical analyses were performed using STATA 11.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. ORs with 95% CIs for the polymorphism MMP1 -1607 1G>2G and cancer were estimated using fixed and random effects models when appropriate. Significantly increased risks were found in overall under the models of 2G vs.1G, 2G2G vs. 1G1G, 2G2G/1G2G vs. 1G1G, and 2G2G vs. 2G1G/1G1G. Significantly elevated risks were observed in colorectal adenoma under the models of 2G vs. 1G, 2G2G vs. 1G1G, 2G2G/1G2G vs. 1G1G, and 2G2G vs. 2G1G/1G1G and lung cancer and head and neck cancer under the models of 2G vs. 1G. We found that significantly elevated risks were observed in Asian population and hospital-based studies in most comparison models tested. Thus, this meta-analysis indicates that the polymorphism MMP1 -1607 1G>2G is significantly associated with a significantly increased risk of cancers and may provide evidence-based medical certificate to study the cancer susceptibility.
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Affiliation(s)
- Lili Lu
- Department of Biology, College of Life and Environmental Sciences, Shanghai Normal University, 100 Guilin Road, 200234, Shanghai, China
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17
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Gao P, Yang JL, Zhao H, You JH, Hu Y. Common polymorphism in the MMP-13 gene may contribute to the risk of human cancers: a meta-analysis. Tumour Biol 2014; 35:10137-48. [PMID: 25023404 DOI: 10.1007/s13277-014-2309-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Accepted: 07/03/2014] [Indexed: 12/28/2022] Open
Abstract
Cancer was viewed to be driven by accumulating genetic abnormalities that generally include chromosomal abnormalities, mutations in tumor-suppressor genes, and oncogenes. The aim of this meta-analysis was to systematically summarize the possible associations between MMP-13 rs2252070 A>G variant and cancer risks. We systematically reviewed studies focusing on MMP-13 polymorphisms with human cancer susceptibility that were published before April 30, 2014. Relevant articles were identified through research of PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (OR) and 95 % confidence interval (95 % CI) were calculated. Eleven independent case-control studies were included in the meta-analysis, which involved 3,465 patients with cancers and 4,073 healthy controls. The results identified a positive association between rs2252070 A>G polymorphism and susceptibility to cancer under five genetic models (all P < 0.05). Ethnicity subgroup analysis implied that significant difference was detected for rs2252070 A>G polymorphism with increased risk of cancers among Asians and Caucasians in majority of the groups. Our findings suggest significant association for MMP-13 rs2252070 A>G to increased susceptibility to human cancer, especially in the progression of lung carcinoma.
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Affiliation(s)
- Ping Gao
- Department of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China
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18
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Yang X, Hu JW, Qiu MT, Li M, Yin R, Wang J, Xu L, Zhang Q. Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies. PLoS One 2014; 9:e87562. [PMID: 24489939 PMCID: PMC3906197 DOI: 10.1371/journal.pone.0087562] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Accepted: 12/21/2013] [Indexed: 12/11/2022] Open
Abstract
Background and Objective Evidence has shown that matrix metalloproteinases-3 (MMP3) is important for cancer progression. Recent studies about the association between the -1171(5A>6A) polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results. Methodology/Principal Findings We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A) polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A) polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR = 0.74, 95%CI: 0.60—0.91; I2 = 1.9%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR = 0.77, 95%CI: 0.64—0.94; I2 = 29.0%). Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR = 0.68, 95%CI: 0.52—0.90; I2 = 26.7%), heterozygote comparison (6A/5A vs. 5A/5A: OR = 0.75, 95%CI: 0.58—0.98; I2 = 0.0%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR = 0.69, 95%CI: 0.54—0.88; I2 = 0.5%). It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR = 1.92, 95%CI: 1.25—2.96; I2 = 72.7%). Conclusion This meta-analysis suggests that the -1171(5A>6A) polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer.
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Affiliation(s)
- Xin Yang
- The First Clinical College of Nanjing Medical University, Nanjing, China
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
| | - Jing-Wen Hu
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
| | - Man-Tang Qiu
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
| | - Ming Li
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
| | - Rong Yin
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
| | - Jie Wang
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
- Department of Scientific Research, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Nanjing, China
| | - Lin Xu
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
- * E-mail: (LX); (QZ)
| | - Qin Zhang
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China
- * E-mail: (LX); (QZ)
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19
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Zhang LF, Mi YY, Cao Q, Wang W, Qin C, Wei JF, Zhou YJ, Li YF, Tang M, Liu WM, Zhang W, Zou JG. Update analysis of studies on the MMP-9 -1562 C>T polymorphism and cancer risk. Mol Biol Rep 2011; 39:3435-41. [PMID: 21717058 DOI: 10.1007/s11033-011-1115-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2011] [Accepted: 06/17/2011] [Indexed: 10/18/2022]
Abstract
Polymorphisms in the matrix metalloproteinase (MMP) gene have been hypothesized to be functional and may contribute to genetic susceptibility to cancers. The common sequence variation in MMP-9 -1562 C>T (rs3918242), has been involved in cancer risk. However, results of the related published studies were somewhat controversial and underpowered in general. To clarify the role of MMP-9 -1562 C>T genotype in global cancer, we performed a meta-analysis of all the available published studies involving 4,124 cancer patients and 4,728 control subjects. The overall results indicated that there was no major association of the variant on cancer risk. However, stratified analysis by cancer type showed that the MMP-9 -1562 C>T polymorphism has a lower risk in colorectal cancer (OR = 0.80, 95%CI = 0.66-0.96, P (heterogeneity) = 0.391) and lung cancer (OR = 0.70, 95%CI = 0.51-0.96, P (heterogeneity) = 0.959) by allelic contrast. Furthermore, association of the MMP-9 -1562 C>T polymorphism and cancer risk was also observed in hospital-based studies under the dominant genetic model (OR = 0.87, 95%CI = 0.78-0.97, P (heterogeneity) = 0.355), allelic contrast (OR = 0.85, 95%CI = 0.75-0.96, P (heterogeneity) = 0.271) and heterozygote comparison (OR = 0.89, 95%CI = 0.79-0.99, P (heterogeneity) = 0.402). This pooled analysis showed evidence that the MMP-9 -1562 C>T polymorphism may decrease both the colorectal and lung cancer risk. Further prospective studies with larger numbers of participants worldwide are required to evaluate the association in more detail.
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Affiliation(s)
- Li-Feng Zhang
- Department of Urology, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, 213003, Jiangsu Province, China
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20
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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: 19] [Impact Index Per Article: 1.4] [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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21
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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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Peng B, Cao L, Wang W, Xian L, Jiang D, Zhao J, Zhang Z, Wang X, Yu L. Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and cancer risk: a meta-analysis of 50 case-control studies. Mutagenesis 2009; 25:41-8. [PMID: 19843588 DOI: 10.1093/mutage/gep041] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Matrix metalloproteinase (MMP) 1 and MMP3 are enzymes that degrade the extracellular matrix and have been implicated to play an important role in cancer development. Many studies have been carried out on the association between polymorphisms of MMP1 -1607 1G>2G and MMP3 -1171 5A>6A and cancer risk. However, results from these studies remain inconclusive. Here, we performed a meta-analysis of >38 000 subjects to better assess the purported associations. For MMP1, -1607 2G/2G genotype carriers were found to have an increased risk of colorectal cancer [2G/2G versus 2G/1G + 1G/1G, odds ratio (OR) = 1.48, 95% confidence interval (CI) (1.26-1.74), P(heterogeneity) = 0.066, I(2) = 49.3%], head and neck cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.61, 95% CI (1.26-2.07), P(heterogeneity) = 0.002, I(2) = 64.7%] and renal cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.82, 95% CI (1.38-2.39), P(heterogeneity) = 0.589, I(2) = 0.0%] risk. For MMP3, no association was found between -1171 5A>6A polymorphism and cancer risk in the overall group [6A versus 5A, OR = 1.00, 95% CI (0.95-1.05), P(heterogeneity) = 0.124, I(2) = 24.9%] and individual cancer subgroups, but stratified analysis by smoking status showed that this polymorphism had different effects on smokers and non-smokers under recessive genetic model. In summary, our study suggests that MMP1 -1607 2G may be associated with an increased cancer risk for certain types of cancers, MMP3 -1171 5A>6A may not be a major risk factor for cancer, but it may be modified by certain environmental factors. Future studies with larger sample sizes are warranted to further evaluate these associations in more detail.
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Affiliation(s)
- Bo Peng
- State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, People's Republic of China
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Dong X, Zhou G, Zhai Y, Zhang H, Yang H, Zhi L, Zhang X, Chu J, He F. Association of DLC1 gene polymorphism with susceptibility to hepatocellular carcinoma in Chinese hepatitis B virus carriers. Cancer Epidemiol 2009; 33:265-70. [PMID: 19766077 DOI: 10.1016/j.canep.2009.08.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2009] [Revised: 08/24/2009] [Accepted: 08/25/2009] [Indexed: 11/18/2022]
Abstract
BACKGROUND Lost or downexpression of the gene deleted in liver cancer 1 (DLC1) has been implicated in the development of hepatocellular carcinoma (HCC). We examined the relationship between DLC1 polymorphisms and HCC risk among Chinese. METHODS Three DLC1 polymorphisms, Ex11+255T>G (rs3739298), Ex11-620G>A (rs532841) and IVS19+108C>T (rs621554), were genotyped in 434 patients with HCC and 480 controls by PCR-RFLP. The associations with the susceptibility to HCC were evaluated while controlling for confounding factors. RESULTS We observed significantly increased susceptibility to HCC for the C/C genotype compared with T/T of IVS19+108C>T in the HBV carriers (OR=2.95, 95% CI, 1.65-5.26, P<0.001). Compared with the haplotype G-A-T (in order of Ex11+255T>G, Ex11-620G>A and IVS19+108C>T), the haplotype T-G-C was also significantly associated with an increased susceptibility to HCC among HBV carriers (OR=2.16, 95% CI, 1.08-4.35, P=0.009). The stratified analysis indicated no modification of the confounding factors on the increased susceptibility to HCC related to the DLC1 polymorphism/haplotype. CONCLUSIONS Our findings suggest that DLC1 genetic polymorphism or haplotype play a role in mediating the susceptibility to HBV-related HCC.
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Affiliation(s)
- Xiaoqun Dong
- The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
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Li Y, Jia JH, Kang S, Zhang XJ, Zhao J, Wang N, Zhou RM, Sun DL, Duan YN, Wang DJ. The functional polymorphisms on promoter region of matrix metalloproteinase-12, -13 genes may alter the risk of epithelial ovarian carcinoma in Chinese. Int J Gynecol Cancer 2009; 19:129-33. [PMID: 19258954 DOI: 10.1111/igc.0b013e31819a1d8e] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUNDS AND AIMS Growing evidences indicate that single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) gene promoter may alter MMPs protein expression levels to influence malignant tumors developing and progressing. Our study was to assess the effects of the SNPs in the promoter region of MMP-12 and MMP-13 on the risk of epithelial ovarian carcinoma (EOC) developing and progressing. METHODS MMP-12 A-82G and MMP-13 A-77G SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism in 256 EOC patients and 329 controls. RESULTS The A/G genotype frequency of MMP-12 was significantly higher in patients than in controls (7.0% vs 3.3%, P = 0.04); similarly, the frequency of MMP-12 82G allele was higher in patients too (P = 0.04). Compared with A/A genotype, A/G genotype significantly increased the risk of EOC (odds ratio, 2.19; 95% confidence interval, 1.01-4.72). Age-stratified analysis showed that individuals with A/G genotype had a higher risk in the final diagnosis aged younger than 50 years. We observed no overall association between MMP-13-77A/G polymorphism and EOC. However, an elevated positive association was observed for A/A versus G/G + A/G genotypes in mucinous ovarian cancer. Combining the analyzed 2 SNPs, the haplotype distributions in patients were not significantly different from that in controls. CONCLUSION These results suggested that the G allele of the MMP-12 82A/G polymorphism might be a risk factor for the development and progression of EOC and that the A/A genotype of MMP-13-77A/G polymorphism was associated with special pathological subtype and clinical stage in EOC at least in Chinese women.
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Affiliation(s)
- Yan Li
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China.
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Yuan X, Zhou G, Zhai Y, Xie W, Cui Y, Cao J, Zhi L, Zhang H, Yang H, Zhang X, Qiu W, Peng Y, Zhang X, Yu L, Xia X, He F. Lack of association between the functional polymorphisms in the estrogen-metabolizing genes and risk for hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 2009; 17:3621-7. [PMID: 19064581 DOI: 10.1158/1055-9965.epi-08-0742] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Estrogens have been proposed to act as tumor promoters and induce hepatocarcinogenesis. Recently, we observed a significant association between the risk for hepatocellular carcinoma and the polymorphisms of the estrogen receptor (ESR) alpha (ESR1) gene, supporting the hypothesis of involvement for the estrogen-ESR axis in the estrogen-induced hepatocarcinogenesis. In this study, based on another hypothesis in which estrogen metabolites can directly cause DNA damage and affect tumor initiation, we examined whether the polymorphisms of the estrogen-metabolizing enzymes (EME), which are involved in biogenesis (CYP17, CYP19), bioavailability (CYP1A1, CYP1B1), and degradation (catechol-O-methyltransferase) of the estrogens, have any bearing on the risk for hepatocellular carcinoma. Seven functional polymorphisms in five EMEs (CYP17 MspAI site, CYP19 Trp39Arg, Ile462Val and MspI site in CYP1A1, CYP1B1 Val432Leu, and Ala72Ser and Val158Met in catechol-O-methyltransferase) were genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PCR-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk for hepatocellular carcinoma was observed with the seven polymorphisms in hepatitis B virus carriers and non-hepatitis B virus carriers after correction for multiple comparisons. After stratification by common confounding factors of hepatocellular carcinoma, the EME polymorphism remained no significant association with the hepatocellular carcinoma risk. Furthermore, no signs of gene-gene interactions were observed for each combination of the seven polymorphisms. Our findings suggest that the polymorphisms of EMEs may not contribute significantly to the risk for hepatocellular carcinoma.
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Affiliation(s)
- Xiaoyan Yuan
- The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China
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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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Nasr HB, Mestiri S, Chahed K, Bouaouina N, Gabbouj S, Jalbout M, Chouchane L. Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (–1562) C/T promoter polymorphisms: Susceptibility and prognostic implications in nasopharyngeal carcinomas. Clin Chim Acta 2007; 384:57-63. [PMID: 17599818 DOI: 10.1016/j.cca.2007.05.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2007] [Revised: 05/23/2007] [Accepted: 05/23/2007] [Indexed: 11/18/2022]
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas. METHODS The variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. RESULTS No association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR=2.27; p=0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR=2.90; p=0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p=0.03). CONCLUSIONS The genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.
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Affiliation(s)
- Hela Ben Nasr
- Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, 5019 Monastir, Tunisia.
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