Download PDF
CC BY 4.0 · Rev Bras Ginecol Obstet 2018; 40(10): 620-624
DOI: 10.1055/s-0038-1673366
Original Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Association between Matrix Metallopeptidase 9 Polymorphism and Breast Cancer Risk

Associação entre o polimorfismo do gene metalopeptidase de matriz 9 e o risco de câncer de mama
Rogério Tadeu Felizi
1   Department of Gynecology, Faculty of Medicine of ABC, Santo André, SP, Brazil
,
Melissa Gonzalez Veiga
1   Department of Gynecology, Faculty of Medicine of ABC, Santo André, SP, Brazil
,
Ivo Carelli Filho
1   Department of Gynecology, Faculty of Medicine of ABC, Santo André, SP, Brazil
,
Ricardo Peres do Souto
2   Department of Biochemistry, Faculty of Medicine of ABC, Santo André, SP, Brazil
,
César Eduardo Fernandes
1   Department of Gynecology, Faculty of Medicine of ABC, Santo André, SP, Brazil
,
Emerson Oliveira
1   Department of Gynecology, Faculty of Medicine of ABC, Santo André, SP, Brazil
› Author Affiliations
Further Information

Publication History

02 May 2018

19 July 2018

Publication Date:
23 October 2018 (online)

   Permissions and Reprints

Abstract

Objective Epidemiological studies have shown evidence of the effect of genetic variations in the pathogenesis of breast cancer and have suggested a relationship of the disease with genetic polymorphisms. Matrix metallopeptidase 9 (MMP-9) is a collagenase responsible for the degradation of type IV collagen, the major component of the basement membrane, and other essential extra cellular matrix components, being involved in the tumor cell invasion and metastasis. Our objective was to evaluate the relationship between the MMP-9-1562 C/T polymorphism (rs 3918242) and the risk of developing breast cancer.

Methods In this case-control study, the frequency of the MMP-9-1562 C/T polymorphism (rs 3918242) was determined in 148 women with breast cancer and 245 women without the disease. The DNA was extracted from plasma samples, and the gene was amplified by polymerase chain reaction (PCR); the presence of the polymorphism was determined using restriction enzymes.

Results After adjusting for confounding variables, we found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio [OR] = 1.159, 95% confidence interval [CI]: 0.6625–1.997, p = 0.5964). We also found no association with more advanced disease, the presence of hormone receptors, human epidermal growth factor receptor 2 (HER2) overexpression, or rate of tumor cell proliferation.

Conclusion We did not observe a relationship between MMP-9–1562 C/T polymorphism (rs 3918242) and the occurrence of breast cancer.

Resumo

Objetivo Estudos epidemiológicos vêm demonstrando evidências da influência de variações genéticas na patogênese do câncer de mama, e têm sugerido associação de polimorfismos com uma maior susceptibilidade à doença. A metalopeptidase de matriz 9 (MMP-9) é uma colagenase responsável pela degradação do colágeno tipo IV, o maior componente da membrana basal, e outros componentes essenciais da matriz extra celular, estando envolvido na invasão da célula tumoral e metástase. Nosso objetivo foi avaliar a associação entre o polimorfismo da 1562 C/T (rs 3918242) do gene MMP-9 e o desenvolvimento da neoplasia mamária.

Métodos Neste estudo caso–controle, a frequência de polimorfismo 1562 C/T (rs 3918242) do MMP-9 foi determinada em 148 mulheres com câncer de mama e 245 mulheres sem a doença. O DNA foi extraído do plasma e o gene foi amplificado por meio de reação em cadeia da polimerase (RCP). O polimorfismo foi determinado por enzimas de restrição.

Resultados O polimorfismo, após o ajuste para variáveis confundidoras, não foi associado com a ocorrência de câncer de mama (razão de possibilidade [RP] = 1,159, intervalo de confiança de 95% [IC95]: 0,6625–1,997, p = 0,5964). Também não foi demonstrado associação com estadiamentos mais avançados, presença de receptores hormonais, superexpressão de HER2 e tampouco com a taxa de proliferação celular do tumor.

Conclusão Não observamos relação entre o polimorfismo 1562 C/T (rs 3918242) do gene MMP-9 e a ocorrência de câncer de mama.

Keywords

MMP-9 metalloproteinase - breast cancer - genetic polymorphism - genetics - single-nucleotide polymorphisms

Palavras-chave

metaloproteinase MMP-9 - câncer de mama - polimorfismo genético - genética - polimorfismos de nucleotídeo único

Contributors

Felizi R. T., Veiga M. G., Carelli Filho I., Souto R. P., Fernandes C. E. and Oliveira E. contributed with the project and the interpretation of data, writing of the article, critical review of the intellectual content and final approval of the version to be published.


 

  • References

  • 1 Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Estimativa 2018: Incidência de Câncer no Brasil. Rio de Janeiro, RJ: INCA; 2017. http://www.inca.gov.br/estimativa/2018/estimativa-2018.pdf . Accessed December 17, 2017
    PubMedGoogle Scholar
  • 2 Zhou LP, Yao F, Luan H. , et al. CYP3A4*1B polymorphism and cancer risk: a HuGE review and meta-analysis. Tumour Biol 2013; 34 (02) 649-660 . Doi: 10.1007/s13277-012-0592-z
    CrossrefPubMedGoogle Scholar
  • 3 Newman B, Austin MA, Lee M, King MC. Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc Natl Acad Sci U S A 1988; 85 (09) 3044-3048 . Doi: 10.1073/pnas.85.9.3044
    CrossrefPubMedGoogle Scholar
  • 4 Dunning AM, Healey CS, Pharoah PDP, Teare MD, Ponder BAJ, Easton DF. A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1999; 8 (10) 843-854
    PubMedGoogle Scholar
  • 5 Belkin AM, Akimov SS, Zaritskaya LS, Ratnikov BI, Deryugina EI, Strongin AY. Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion. J Biol Chem 2001; 276 (21) 18415-18422 . Doi: 10.1074/jbc.M010135200
    CrossrefPubMedGoogle Scholar
  • 6 Przybylowska K, Kluczna A, Zadrozny M. , et al. Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer. Breast Cancer Res Treat 2006; 95 (01) 65-72 . Doi: 10.1007/s10549-005-9042-6
    CrossrefPubMedGoogle Scholar
  • 7 Savinov AY, Remacle AG, Golubkov VS. , et al. Matrix metalloproteinase 26 proteolysis of the NH2-terminal domain of the estrogen receptor beta correlates with the survival of breast cancer patients. Cancer Res 2006; 66 (05) 2716-2724
    CrossrefPubMedGoogle Scholar
  • 8 Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002; 2 (03) 161-174 . Doi: 10.1038/nrc745
    CrossrefPubMedGoogle Scholar
  • 9 Folgueras AR, Pendás AM, Sánchez LM, López-Otín C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol 2004; 48 (5-6): 411-424 . Doi: 10.1387/ijdb.041811af
    CrossrefPubMedGoogle Scholar
  • 10 Lemaître V, D'Armiento J. Matrix metalloproteinases in development and disease. Birth Defects Res C Embryo Today 2006; 78 (01) 1-10 . Doi: 10.1002/bdrc.20065
    CrossrefPubMedGoogle Scholar
  • 11 Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 1980; 284 (5751): 67-68
    CrossrefPubMedGoogle Scholar
  • 12 Duffy MJ, Maguire TM, Hill A, McDermott E, O'Higgins N. Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2000; 2 (04) 252-257
    CrossrefPubMedGoogle Scholar
  • 13 St Jean PL, Zhang XC, Hart BK. , et al. Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease. Ann Hum Genet 1995; 59 (Pt 1): 17-24 . Doi: 10.1111/j.1469-1809.1995.tb01602.x
    CrossrefPubMedGoogle Scholar
  • 14 Zhang X, Jin G, Li J, Zhang L. Association between four MMP-9 polymorphisms and breast cancer risk: a meta-analysis. Med Sci Monit 2015; 21: 1115-1123 . Doi: 10.12659/MSM.893890
    CrossrefPubMedGoogle Scholar
  • 15 Yousef EM, Tahir MR, St-Pierre Y, Gaboury LA. MMP-9 expression varies according to molecular subtypes of breast cancer. BMC Cancer 2014; 14: 609 . Doi: 10.1186/1471-2407-14-609
    CrossrefPubMedGoogle Scholar
  • 16 Zhang B, Ye S, Herrmann SM. , et al. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 1999; 99 (14) 1788-1794 . Doi: 10.1161/01.CIR.99.14.1788
    CrossrefPubMedGoogle Scholar
  • 17 Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann Oncol 2015; 26 (07) 1291-1299 . Doi: 10.1093/annonc/mdv022
    CrossrefPubMedGoogle Scholar
  • 18 Rahimi Z, Yari K, Rahimi Z. Matrix metalloproteinase-9 -1562T allele and its combination with MMP-2 -735 C allele are risk factors for breast cancer. Asian Pac J Cancer Prev 2015; 16 (03) 1175-1179
    CrossrefPubMedGoogle Scholar
  • 19 Padala C, Tupurani MA, Puranam K. , et al. Synergistic effect of collagenase-1 (MMP1), stromelysin-1 (MMP3) and gelatinase-B (MMP9) gene polymorphisms in breast cancer. PLoS One 2017; 12 (09) e0184448 . Doi: 10.1371/journal.pone.0184448
    CrossrefPubMedGoogle Scholar
  • 20 Merdad A, Karim S, Schulten HJ. , et al. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Res 2014; 34 (03) 1355-1366
    PubMedGoogle Scholar
  • 21 Roehe AV, Frazzon AP, Agnes G, Damin AP, Hartman AA, Graudenz MS. Detection of polymorphisms in the promoters of matrix metalloproteinases 2 and 9 genes in breast cancer in South Brazil: preliminary results. Breast Cancer Res Treat 2007; 102 (01) 123-124 . Doi: 10.1007/s10549-006-9273-1
    CrossrefPubMedGoogle Scholar
  • 22 Zhou P, Du LF, Lv GQ. , et al. Current evidence on the relationship between four polymorphisms in the matrix metalloproteinases (MMP) gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 2011; 127 (03) 813-818 . Doi: 10.1007/s10549-010-1294-0
    CrossrefPubMedGoogle Scholar
  • 23 Jones JL, Walker RA. Control of matrix metalloproteinase activity in cancer. J Pathol 1997; 183 (04) 377-379 . Doi: 10.1002/(SICI)1096-9896(199712)183:4<377:AID-PATH951>3.0.CO;2-R
    CrossrefPubMedGoogle Scholar
  • 24 Liu D, Guo H, Li Y, Xu X, Yang K, Bai Y. Association between polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and risk of cancer metastasis: a meta-analysis. PLoS One 2012; 7 (02) e31251 . Doi: 10.1371/journal.pone.0031251
    CrossrefPubMedGoogle Scholar
  • 25 Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol 2001; 2 (03) 133-140 . Doi: 10.1016/S1470-2045(00)00254-0
    CrossrefPubMedGoogle Scholar
  • 26 Soroush A, Farshchian N, Komasi S, Izadi N, Amirifard N, Shahmohammadi A. The role of oral contraceptive pills on increased risk of breast cancer in Iranian populations: a meta-analysis. J Cancer Prev 2016; 21 (04) 294-301 . Doi: 10.15430/JCP.2016.21.4.294
    CrossrefPubMedGoogle Scholar
  • 27 Cauchi JP, Camilleri L, Scerri C. Environmental and lifestyle risk factors of breast cancer in Malta-a retrospective case-control study. EPMA J 2016; 7: 20 . Doi: 10.1186/s13167-016-0069-z
    CrossrefPubMedGoogle Scholar
  • 28 Appel SJ, Cleiment RJ. Identifying women at risk for hereditary breast and ovarian cancer syndrome utilizing breast care nurse navigation at mammography and imaging centers. J Natl Black Nurses Assoc 2015; 26 (02) 17-26
    PubMedGoogle Scholar