MMP1 rs1799750 Single Nucleotide Polymorphism and Lung Cancer Risk: A Meta-analysis

  • Hu, Jiang (Department of Oncology, Taihe Hospital Affiliated with Hubei University of Medicine) ;
  • Pan, Jun (Department of Oncology, Taihe Hospital Affiliated with Hubei University of Medicine) ;
  • Luo, Zhi-Guo (Department of Oncology, Taihe Hospital Affiliated with Hubei University of Medicine)
  • Published : 2012.12.31


Background: Numerous studies have investigated the association of matrix metalloproteinase 1 (MMP1) rs1799750 single nucleotide polymorphism with lung cancer susceptibility, but the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate any possible association. Methods: We searched publications from MEDLINE, EMBASE and CNKI databases which assessed links between the MMP1 rs1799750 polymorphism and lung cancer risk. We calculated the pooled odds ratio (OR) and its 95% confidence interval (95%CI) using either fixed-effects or random-effects models. Results: The meta-analysis was based on 9 publications encompassing 4,823 cases and 4,298 controls. The overall results suggested there was a significant association between the MMP1 rs1799750 polymorphism and lung cancer risk (1G vs. 2G: OR = 0.83, 95%CI = 0.73-0.94; 1G1G vs. 2G2G: OR = 0.73, 95%CI = 0.59-0.92; 1G1G vs. 1G2G/2G2G: OR = 0.87, 95%CI = 0.79-0.97; 1G1G/1G2G vs. 2G2G: OR = 0.78, 95%CI = 0.64-0.95). In the subgroup analysis by ethnicity, the association was still obvious in Asians (all P values < 0.05), but there was no association in Caucasians (all P values > 0.05). Conclusions: The MMP1 rs1799750 polymorphism is associated with decreased lung cancer risk, and a race-specific effect may exist in this association.


MMP1;lung cancer;single nucleotide polymorphism;meta;analysis;ethnic groups


  1. Zhang WQ, Lin H, Zhou YA, et al (2006). [Association of MMP1 -1607(1G>2G) single nucleotide polymorphism with susceptibility to lung cancer in Northwestern Chinese population of Han nationality]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 23, 313-5.
  2. Zhou J, Brinckerhoff C, Lubert S, et al (2011). Analysis of matrix metalloproteinase-1 gene polymorphisms and expression in benign and malignant breast tumors. Cancer Invest, 29, 599-607.
  3. Zhou Y, Yu C, Miao X, et al (2005). Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung cancer susceptibility. Carcinogenesis, 26, 1117-21.
  4. Zhu Y, Spitz MR, Lei L, et al (2001). A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. Cancer Res, 61, 7825-9.
  5. Gonzalez-Arriaga P, Lopez-Cima MF, Fernandez-Somoano A, et al (2008). Polymorphism +17 C/G in matrix metalloprotease MMP8 decreases lung cancer risk. BMC Cancer, 8, 378.
  6. Hart K, Landvik NE, Lind H, et al (2011). A combination of functional polymorphisms in the CASP8, MMP1, IL10 and SEPS1 genes affects risk of non-small cell lung cancer. Lung Cancer, 71, 123-9.
  7. Herbst RS, Heymach JV, Lippman SM (2008). Lung cancer. N Engl J Med, 359, 1367-80.
  8. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60.
  9. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  10. Kimman M, Norman R, Jan S, et al (2012). The Burden of Cancer in Member Countries of the Association of Southeast Asian Nations (ASEAN). Asian Pac J Cancer Prev, 13, 411-20.
  11. Liu D, Duan W, Guo H, et al (2011). Meta-analysis of associations between polymorphisms in the promoter regions of matrix metalloproteinases and the risk of colorectal cancer. Int J Colorectal Dis, 26, 1099-105.
  12. Liu D, Guo H, Li Y, et al (2012). Association between polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and risk of cancer metastasis: a meta-analysis. PLoS One, 7, e31251.
  13. Liu L, Wu J, Wu C, et al (2011). A functional polymorphism (-1607 1G-->2G) in the matrix metalloproteinase-1 promoter is associated with development and progression of lung cancer. Cancer, 117, 5172-81.
  14. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  15. Nelson AR, Fingleton B, Rothenberg ML, et al (2000). Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol, 18, 1135-49.
  16. Peng B, Cao L, Wang W, et al (2010). Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and cancer risk: a meta-analysis of 50 case-control studies. Mutagenesis, 25, 41-8.
  17. Sauter W, Rosenberger A, Beckmann L, et al (2008). Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer. Cancer Epidemiol Biomarkers Prev, 17, 1127-35.
  18. Su L, Zhou W, Asomaning K, et al (2006). Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer. Carcinogenesis, 27, 1024-9.
  19. Wei W, Liang X, Weng X (2007). The association of MMP-1-1607(1 G-2G) single nucleotide polymorpllism with the susceptibility to non-small cell lung carcinoma in Guizhou Han Nationality. JOURNAL OF GUIYANG MEDICAL COLLEGE, 32, 267-70.
  20. Xiao H, Ding J, Gao S, et al (2011). Never smokers with lung cancer: analysis of genetic variants. Asian Pac J Cancer Prev, 12, 2807-9.
  21. Yamamura T, Nakanishi K, Hiroi S, et al (2002). Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in nonsmall cell lung carcinomas. Lung Cancer, 35, 249-55.
  22. Attia J, Thakkinstian A, D'Este C (2003). Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol, 56, 297-303.
  23. Brennan P, Hainaut P, Boffetta P (2011). Genetics of lung-cancer susceptibility. Lancet Oncol, 12, 399-408.
  24. Cheng X (2007). Correlation of single nucleotide polymorphism in the matrix metallola'oteinase-1 promoter region (-1607)1G/2G with risk of lung cancer. J Shangxi Med Univ, 38, 777-9.
  25. Chen Y, Nixon NB, Dawes PT, et al (2012). Influence of variations across the MMP-1 and -3 genes on the serum levels of MMP- 1 and -3 and disease activity in rheumatoid arthritis. Genes Immun, 13, 29-37.
  26. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  27. Egeblad M, Werb Z (2002). New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer, 2, 161-74.
  28. Fang S, Jin X, Wang R, et al (2005). Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China. Carcinogenesis, 26, 481-6.
  29. Goldstraw P, Ball D, Jett JR, et al (2011). Non-small-cell lung cancer. Lancet, 378, 1727-40.

Cited by

  1. Matrix metalloproteinases and genetic mouse models in cancer research: a mini-review vol.36, pp.1, 2015,
  2. The polymorphism MMP1 −1607 (1G>2G) is associated with a significantly increased risk of cancers from a meta-analysis vol.36, pp.3, 2015,