This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hu, Z. Articles by Shen, H. Search for Related Content PubMed PubMed Citation Articles by Hu, Z. Articles by Shen, H.

Functional Polymorphisms of Matrix Metalloproteinase-9 Are Associated with Risk of Occurrence and Metastasis of Lung Cancer

Authors' Affiliations: ¹ Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health; ² Department of Thoracic Surgery, Jiangsu Cancer Hospital; ³ Department of Thoracic and Cardiac Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; ⁴ Institute of Genetics, Fudan University, Shanghai, China; and ⁵ Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Hongbing Shen, Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Road, Nanjing 210029, China. Phone: 86-25-868-62747; Fax: 86-25-868-62756; E-mail: hbshen{at}njmu.edu.cn.

Purpose: Matrix metalloproteinase 9 (MMP-9) plays critical roles in cancer development and aggression. Nonsynonymous single-nucleotide polymorphisms (SNP) in the functional domain of the MMP-9 gene may influence substrate and inhibitor binding and contribute to cancer predisposition and aggression.

Patients and Methods: To test our hypothesis that common nonsynonymous SNPs, R279Q, P574R, and R668Q, in MMP-9 are associated with lung cancer development and metastasis, we conducted a case-control study of 744 patients with incident lung cancer and 747 cancer-free controls in Southeast China. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI).

Results: We found that compared with the 279QQ genotype, the 279RR genotype was associated with significant elevated risk of lung cancer with metastasis (adjusted OR, 1.79; 95% CI, 1.03-3.08), whereas the 574PR heterozygote and 574PP homozygote had 1.46-fold (95% CI, 0.94-2.26) and 1.69-fold elevated risk (95% CI, 1.10-2.60), respectively, compared with the 574RR genotype. When we examined the combined effect of R279Q and P574R and used the 279R and 574P as the risk alleles, a significantly increased risk of lung cancer was associated with both the genotypes containing "1 to 2 risk alleles" (adjusted OR, 2.16; 95% CI, 1.30-3.59) and containing ">2 risk alleles" (adjusted OR, 2.44; 95% CI, 1.48-4.03), and it was more pronounced in 290 lung cancer cases with metastasis [adjusted OR, 2.30 (95% CI, 1.09-4.85) for the 1 to 2 risk alleles subgroup and adjusted OR, 2.82 (95% CI, 1.35-5.88) for the >2 risk alleles subgroup], compared with those without any risk alleles. However, no overall significant associations were observed between R668Q and lung cancer risk in this study population.

Conclusion: These findings indicate that the potentially functional polymorphisms, MMP-9 P574R and R279Q, may confer the biomarker in the occurrence and metastasis of primary lung cancer. Further functional studies including these two genetic variants are warranted to confirm our findings.

This article has been cited by other articles:

				Y. Tang, J. Zhu, L. Chen, L. Chen, S. Zhang, and J. Lin Associations of Matrix Metalloproteinase-9 Protein Polymorphisms with Lymph Node Metastasis but not Invasion of Gastric Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2870 - 2877. [Abstract] [Full Text] [PDF]

				A. K. Kader, J. Liu, L. Shao, C. P. Dinney, J. Lin, Y. Wang, J. Gu, H. B. Grossman, and X. Wu Matrix Metalloproteinase Polymorphisms Are Associated with Bladder Cancer Invasiveness Clin. Cancer Res., May 1, 2007; 13(9): 2614 - 2620. [Abstract] [Full Text] [PDF]

				Y. Zhai, W. Qiu, X.-J. Dong, X.-M. Zhang, W.-M. Xie, H.-X. Zhang, X.-Y. Yuan, G.-Q. Zhou, and F.-C. He Functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12 and MMP-13 are not associated with hepatocellular carcinoma risk Gut, March 1, 2007; 56(3): 445 - 447. [Full Text] [PDF]

				A. K. Kader, L. Shao, C. P. Dinney, M. B. Schabath, Y. Wang, J. Liu, J. Gu, H. B. Grossman, and X. Wu Matrix Metalloproteinase Polymorphisms and Bladder Cancer Risk Cancer Res., December 15, 2006; 66(24): 11644 - 11648. [Abstract] [Full Text] [PDF]

				S. Han, J. D. Ritzenthaler, S. V. Sitaraman, and J. Roman Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells J. Biol. Chem., October 6, 2006; 281(40): 29614 - 29624. [Abstract] [Full Text] [PDF]