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Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer.

Publication ,  Journal Article
Hu, Z; Huo, X; Lu, D; Qian, J; Zhou, J; Chen, Y; Xu, L; Ma, H; Zhu, J; Wei, Q; Shen, H
Published in: Clin Cancer Res
August 1, 2005

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.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

August 1, 2005

Volume

11

Issue

15

Start / End Page

5433 / 5439

Location

United States

Related Subject Headings

  • Smoking
  • Risk
  • Regression Analysis
  • Protein Structure, Tertiary
  • Protein Binding
  • Polymorphism, Single Nucleotide
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
 

Citation

APA
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ICMJE
MLA
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Hu, Z., Huo, X., Lu, D., Qian, J., Zhou, J., Chen, Y., … Shen, H. (2005). Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer. Clin Cancer Res, 11(15), 5433–5439. https://doi.org/10.1158/1078-0432.CCR-05-0311
Hu, Zhibin, Xiang Huo, Daru Lu, Ji Qian, Jiannong Zhou, Yijiang Chen, Lin Xu, et al. “Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer.Clin Cancer Res 11, no. 15 (August 1, 2005): 5433–39. https://doi.org/10.1158/1078-0432.CCR-05-0311.
Hu Z, Huo X, Lu D, Qian J, Zhou J, Chen Y, et al. Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer. Clin Cancer Res. 2005 Aug 1;11(15):5433–9.
Hu, Zhibin, et al. “Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer.Clin Cancer Res, vol. 11, no. 15, Aug. 2005, pp. 5433–39. Pubmed, doi:10.1158/1078-0432.CCR-05-0311.
Hu Z, Huo X, Lu D, Qian J, Zhou J, Chen Y, Xu L, Ma H, Zhu J, Wei Q, Shen H. Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer. Clin Cancer Res. 2005 Aug 1;11(15):5433–5439.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

August 1, 2005

Volume

11

Issue

15

Start / End Page

5433 / 5439

Location

United States

Related Subject Headings

  • Smoking
  • Risk
  • Regression Analysis
  • Protein Structure, Tertiary
  • Protein Binding
  • Polymorphism, Single Nucleotide
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis