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Published in: Breast Cancer Research 4/2005

Open Access 01-08-2005 | Research article

Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study

Authors: Aesun Shin, Qiuyin Cai, Xiao-Ou Shu, Yu-Tang Gao, Wei Zheng

Published in: Breast Cancer Research | Issue 4/2005

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Abstract

Introduction

Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine.

Methods

Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival.

Results

The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00).

Conclusion

This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted.
Appendix
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Literature
1.
go back to reference Vu TH, Werb Z: Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 2000, 14: 2123-2133. 10.1101/gad.815400.CrossRefPubMed Vu TH, Werb Z: Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 2000, 14: 2123-2133. 10.1101/gad.815400.CrossRefPubMed
2.
go back to reference Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002, 2: 161-174. 10.1038/nrc745.CrossRefPubMed Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002, 2: 161-174. 10.1038/nrc745.CrossRefPubMed
3.
go back to reference Ye S: Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol. 2000, 19: 623-629. 10.1016/S0945-053X(00)00102-5.CrossRefPubMed Ye S: Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol. 2000, 19: 623-629. 10.1016/S0945-053X(00)00102-5.CrossRefPubMed
4.
go back to reference Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T: Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. 2003, 253: 269-285. 10.1023/A:1026028303196.CrossRefPubMed Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T: Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. 2003, 253: 269-285. 10.1023/A:1026028303196.CrossRefPubMed
5.
go back to reference Dong Z, Kumar R, Yang X, Fidler IJ: Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell. 1997, 88: 801-810. 10.1016/S0092-8674(00)81926-1.CrossRefPubMed Dong Z, Kumar R, Yang X, Fidler IJ: Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell. 1997, 88: 801-810. 10.1016/S0092-8674(00)81926-1.CrossRefPubMed
6.
go back to reference Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, Pierce RA, Shapiro SD: Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol. 1998, 161: 6845-6852.PubMed Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, Pierce RA, Shapiro SD: Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol. 1998, 161: 6845-6852.PubMed
7.
go back to reference Jormsjo S, Ye S, Moritz J, Walter DH, Dimmeler S, Zeiher AM, Henney A, Hamsten A, Eriksson P: Allele-specific regulation of matrix metalloproteinase-12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease. Circ Res. 2000, 86: 998-1003.CrossRefPubMed Jormsjo S, Ye S, Moritz J, Walter DH, Dimmeler S, Zeiher AM, Henney A, Hamsten A, Eriksson P: Allele-specific regulation of matrix metalloproteinase-12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease. Circ Res. 2000, 86: 998-1003.CrossRefPubMed
8.
go back to reference Lamblin N, Bauters C, Hermant X, Lablanche JM, Helbecque N, Amouyel P: Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease. J Am Coll Cardiol. 2002, 40: 43-48. 10.1016/S0735-1097(02)01909-5.CrossRefPubMed Lamblin N, Bauters C, Hermant X, Lablanche JM, Helbecque N, Amouyel P: Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease. J Am Coll Cardiol. 2002, 40: 43-48. 10.1016/S0735-1097(02)01909-5.CrossRefPubMed
9.
go back to reference Gao YT, Shu XO, Dai Q, Potter JD, Brinton LA, Wen W, Sellers TA, Kushi LH, Ruan Z, Bostick RM, et al: Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study. Int J Cancer. 2000, 87: 295-300. 10.1002/1097-0215(20000715)87:2<295::AID-IJC23>3.0.CO;2-7.CrossRefPubMed Gao YT, Shu XO, Dai Q, Potter JD, Brinton LA, Wen W, Sellers TA, Kushi LH, Ruan Z, Bostick RM, et al: Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study. Int J Cancer. 2000, 87: 295-300. 10.1002/1097-0215(20000715)87:2<295::AID-IJC23>3.0.CO;2-7.CrossRefPubMed
10.
go back to reference Shu XO, Gao YT, Cai Q, Pierce L, Cai H, Ruan ZX, Yang G, Jin F, Zheng W: Genetic polymorphisms in the TGF-beta 1 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study. Cancer Res. 2004, 64: 836-839.CrossRefPubMed Shu XO, Gao YT, Cai Q, Pierce L, Cai H, Ruan ZX, Yang G, Jin F, Zheng W: Genetic polymorphisms in the TGF-beta 1 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study. Cancer Res. 2004, 64: 836-839.CrossRefPubMed
11.
go back to reference Shu XO, Cai Q, Gao YT, Wen W, Jin F, Zheng W: A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2003, 12: 1462-1467.PubMed Shu XO, Cai Q, Gao YT, Wen W, Jin F, Zheng W: A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2003, 12: 1462-1467.PubMed
12.
go back to reference Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, Sandford AJ: The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet. 2002, 11: 569-576. 10.1093/hmg/11.5.569.CrossRefPubMed Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, Sandford AJ: The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet. 2002, 11: 569-576. 10.1093/hmg/11.5.569.CrossRefPubMed
13.
go back to reference Zhang B, Dhillon S, Geary I, Howell WM, Iannotti F, Day IN, Ye S: Polymorphisms in matrix metalloproteinase-1, -3, -9, and -12 genes in relation to subarachnoid hemorrhage. Stroke. 2001, 32: 2198-2202.CrossRefPubMed Zhang B, Dhillon S, Geary I, Howell WM, Iannotti F, Day IN, Ye S: Polymorphisms in matrix metalloproteinase-1, -3, -9, and -12 genes in relation to subarachnoid hemorrhage. Stroke. 2001, 32: 2198-2202.CrossRefPubMed
14.
go back to reference Devlin B, Risch N: A comparison of linkage disequilibrium measures for fine-scale mapping. Genomics. 1995, 29: 311-322. 10.1006/geno.1995.9003.CrossRefPubMed Devlin B, Risch N: A comparison of linkage disequilibrium measures for fine-scale mapping. Genomics. 1995, 29: 311-322. 10.1006/geno.1995.9003.CrossRefPubMed
15.
go back to reference Yang W, Arii S, Gorrin-Rivas MJ, Mori A, Onodera H, Imamura M: Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer. 2001, 91: 1277-1283. 10.1002/1097-0142(20010401)91:7<1277::AID-CNCR1129>3.0.CO;2-H.CrossRefPubMed Yang W, Arii S, Gorrin-Rivas MJ, Mori A, Onodera H, Imamura M: Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer. 2001, 91: 1277-1283. 10.1002/1097-0142(20010401)91:7<1277::AID-CNCR1129>3.0.CO;2-H.CrossRefPubMed
16.
go back to reference Kerkelä E, Ala-aho R, Klemi P, Grenman S, Shapiro SD, Kahari VM, Saarialho-Kere U: Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome. J Pathol. 2002, 198: 258-269. 10.1002/path.1198.CrossRefPubMed Kerkelä E, Ala-aho R, Klemi P, Grenman S, Shapiro SD, Kahari VM, Saarialho-Kere U: Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome. J Pathol. 2002, 198: 258-269. 10.1002/path.1198.CrossRefPubMed
17.
go back to reference Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH: Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol. 1996, 149: 273-282.PubMedPubMedCentral Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH: Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol. 1996, 149: 273-282.PubMedPubMedCentral
18.
go back to reference Zucker S, Vacirca J: Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004, 23: 101-117. 10.1023/A:1025867130437.CrossRefPubMed Zucker S, Vacirca J: Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004, 23: 101-117. 10.1023/A:1025867130437.CrossRefPubMed
19.
go back to reference Ferreras M, Felbor U, Lenhard T, Olsen BR, Delaissé JM: Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett. 2000, 486: 247-251. 10.1016/S0014-5793(00)02249-3.CrossRefPubMed Ferreras M, Felbor U, Lenhard T, Olsen BR, Delaissé JM: Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett. 2000, 486: 247-251. 10.1016/S0014-5793(00)02249-3.CrossRefPubMed
20.
go back to reference Koolwijk P, Sidenius N, Peters E, Sier CF, Hanemaaijer R, Blasi F, van Hinsbergh VW: Proteolysis of the urokinase-type plasminogen activator receptor by metalloproteinase-12: implication for angiogenesis in fibrin matrices. Blood. 2001, 97: 3123-3131. 10.1182/blood.V97.10.3123.CrossRefPubMed Koolwijk P, Sidenius N, Peters E, Sier CF, Hanemaaijer R, Blasi F, van Hinsbergh VW: Proteolysis of the urokinase-type plasminogen activator receptor by metalloproteinase-12: implication for angiogenesis in fibrin matrices. Blood. 2001, 97: 3123-3131. 10.1182/blood.V97.10.3123.CrossRefPubMed
21.
go back to reference Schlesselman JJ: Sample size. Case-Control Studies. 1982, New York: Oxford University Press, 144-150. Schlesselman JJ: Sample size. Case-Control Studies. 1982, New York: Oxford University Press, 144-150.
22.
go back to reference Freedman ML, Reich D, Penney KL, McDonald GJ, Mignault AA, Patterson N, Gabriel SB, Topol EJ, Smoller JW, Pato CN, et al: Assessing the impact of population stratification on genetic association studies. Nat Genet. 2004, 36: 388-393. 10.1038/ng1333.CrossRefPubMed Freedman ML, Reich D, Penney KL, McDonald GJ, Mignault AA, Patterson N, Gabriel SB, Topol EJ, Smoller JW, Pato CN, et al: Assessing the impact of population stratification on genetic association studies. Nat Genet. 2004, 36: 388-393. 10.1038/ng1333.CrossRefPubMed
Metadata
Title
Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study
Authors
Aesun Shin
Qiuyin Cai
Xiao-Ou Shu
Yu-Tang Gao
Wei Zheng
Publication date
01-08-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1033

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