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Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Clinical Cancer Research, 11, 2005, 15, S. 5433-5439 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Hu, Zhibin Huo, Xiang Lu, Daru Qian, Ji Zhou, Jiannong Chen, Yijiang Xu, Lin Ma, Hongxia Zhu, Jingfu Wei, Qingyi Shen, Hongbing Hu, Zhibin Huo, Xiang Lu, Daru Qian, Ji Zhou, Jiannong Chen, Yijiang Xu, Lin Ma, Hongxia Zhu, Jingfu Wei, Qingyi Shen, Hongbing |
|---|---|
| author |
Hu, Zhibin Huo, Xiang Lu, Daru Qian, Ji Zhou, Jiannong Chen, Yijiang Xu, Lin Ma, Hongxia Zhu, Jingfu Wei, Qingyi Shen, Hongbing |
| spellingShingle |
Hu, Zhibin Huo, Xiang Lu, Daru Qian, Ji Zhou, Jiannong Chen, Yijiang Xu, Lin Ma, Hongxia Zhu, Jingfu Wei, Qingyi Shen, Hongbing Clinical Cancer Research Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer Cancer Research Oncology |
| author_sort |
hu, zhibin |
| spelling |
Hu, Zhibin Huo, Xiang Lu, Daru Qian, Ji Zhou, Jiannong Chen, Yijiang Xu, Lin Ma, Hongxia Zhu, Jingfu Wei, Qingyi Shen, Hongbing 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-05-0311 <jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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).</jats:p><jats:p>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 “&gt;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 &gt;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.</jats:p><jats:p>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.</jats:p> Functional Polymorphisms of<i>Matrix Metalloproteinase-9</i>Are Associated with Risk of Occurrence and Metastasis of Lung Cancer Clinical Cancer Research |
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10.1158/1078-0432.ccr-05-0311 |
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American Association for Cancer Research (AACR), 2005 |
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American Association for Cancer Research (AACR), 2005 |
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1078-0432 1557-3265 |
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Clinical Cancer Research |
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| title |
Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_unstemmed |
Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_full |
Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_fullStr |
Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_full_unstemmed |
Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_short |
Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_sort |
functional polymorphisms of<i>matrix metalloproteinase-9</i>are associated with risk of occurrence and metastasis of lung cancer |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-05-0311 |
| publishDate |
2005 |
| physical |
5433-5439 |
| description |
<jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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).</jats:p><jats:p>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 “&gt;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 &gt;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.</jats:p><jats:p>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.</jats:p> |
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| author | Hu, Zhibin, Huo, Xiang, Lu, Daru, Qian, Ji, Zhou, Jiannong, Chen, Yijiang, Xu, Lin, Ma, Hongxia, Zhu, Jingfu, Wei, Qingyi, Shen, Hongbing |
| author_facet | Hu, Zhibin, Huo, Xiang, Lu, Daru, Qian, Ji, Zhou, Jiannong, Chen, Yijiang, Xu, Lin, Ma, Hongxia, Zhu, Jingfu, Wei, Qingyi, Shen, Hongbing, Hu, Zhibin, Huo, Xiang, Lu, Daru, Qian, Ji, Zhou, Jiannong, Chen, Yijiang, Xu, Lin, Ma, Hongxia, Zhu, Jingfu, Wei, Qingyi, Shen, Hongbing |
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| description | <jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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).</jats:p><jats:p>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 “&gt;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 &gt;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.</jats:p><jats:p>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.</jats:p> |
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| imprint | American Association for Cancer Research (AACR), 2005 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2005 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105 |
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| spelling | Hu, Zhibin Huo, Xiang Lu, Daru Qian, Ji Zhou, Jiannong Chen, Yijiang Xu, Lin Ma, Hongxia Zhu, Jingfu Wei, Qingyi Shen, Hongbing 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-05-0311 <jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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).</jats:p><jats:p>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 “&gt;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 &gt;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.</jats:p><jats:p>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.</jats:p> Functional Polymorphisms of<i>Matrix Metalloproteinase-9</i>Are Associated with Risk of Occurrence and Metastasis of Lung Cancer Clinical Cancer Research |
| spellingShingle | Hu, Zhibin, Huo, Xiang, Lu, Daru, Qian, Ji, Zhou, Jiannong, Chen, Yijiang, Xu, Lin, Ma, Hongxia, Zhu, Jingfu, Wei, Qingyi, Shen, Hongbing, Clinical Cancer Research, Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer, Cancer Research, Oncology |
| title | Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_full | Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_fullStr | Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_full_unstemmed | Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_short | Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| title_sort | functional polymorphisms of<i>matrix metalloproteinase-9</i>are associated with risk of occurrence and metastasis of lung cancer |
| title_unstemmed | Functional Polymorphisms ofMatrix Metalloproteinase-9Are Associated with Risk of Occurrence and Metastasis of Lung Cancer |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-05-0311 |