Breast Cancer Research and Treatment

, Volume 103, Issue 1, pp 61–69 | Cite as

Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression

  • Haixin Lei
  • Kari Hemminki
  • Andrea Altieri
  • Robert Johansson
  • Kerstin Enquist
  • Göran Hallmans
  • Per Lenner
  • Asta Försti
Epidemiology

Abstract

The importance of matrix metalloproteinases and their inhibitors in tumor progression is well documented. We wanted to investigate if single nucleotide polymorphisms (SNPs) in the promoter regions of these genes are associated with susceptibility to or progression of breast cancer. In this, so far largest case–control study, we genotyped eight SNPs in the MMP1, MMP2, MMP3, MMP9, MMP13, RECK and TIMP3 genes in a well-characterized breast cancer series of 959 cases and 952 controls from Sweden. Even though we did not correct for multiple comparisons, only a few associations were noted. We observed a moderately increased risk for the TT homozygotes of the MMP9−1562 C/T SNP (OR 1.88, 95% CI 0.97–3.63) and for the C allele carriers of the TIMP3−1296 T/C SNP (OR 1.25, 95% CI 1.05–1.50). In the survival analysis, only the TC heterozygotes of the RECK−420 T/C SNP showed a better survival compared to the TT homozygotes (P = 0.02 in all cases and P = 0.03 in lymph node negative cases). None of the other SNPs conferred an increased breast cancer risk, nor did they correlate with survival. A combination of the −585 TT homozygosity in the RECK gene and the −1296 TT homozygosity in the TIMP3 gene correlated with estrogen and progesterone receptor status (OR 1.81, 95% CI 1.03–3.21 and OR 2.10, 95% CI 1.18–3.86, respectively), and a combination of the −1306 TT homozygosity in the MMP2 gene and the −1562 CC homozygosity in the MMP9 gene with progesterone receptor status (OR 2.34, 95% CI 1.08–5.08). Although our study suggests some correlations between the studied SNPs and the progression of breast cancer, the rarity of the risk genotypes limits their usefulness in the clinic.

Keywords

Breast cancer susceptibility Cancer prognosis Case–control study Polymorphism MMP RECK TIMP 

Notes

Acknowledgements

We thank Åsa Ågren (Department of Public Health and Clinical Medicine/Nutritional Research, UmeÅ University, Sweden) for her efficiency and skill in keeping track of samples and data. We also thank Dagmar Beiße for the technical assistance. The Northern Sweden Breast Cancer Group is appreciated for providing the clinical data. The project was partially funded by Wallenberg Consortium North, Sweden and by a grant from EU (LSHC-CT−2004–503465 to KH).

Supplementary material

10549_2006_9345_MOESM1_ESM.doc (114 kb)
Supplementary material

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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Haixin Lei
    • 1
  • Kari Hemminki
    • 1
    • 2
  • Andrea Altieri
    • 1
  • Robert Johansson
    • 3
  • Kerstin Enquist
    • 4
  • Göran Hallmans
    • 4
  • Per Lenner
    • 3
  • Asta Försti
    • 1
    • 2
  1. 1.Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Center for Family MedicineKarolinska InstituteHuddingeSweden
  3. 3.Department of OncologyNorrlands University HospitalUmeåSweden
  4. 4.Department of Public Health and Clinical Medicine/Nutritional ResearchUmeå UniversityUmeåSweden

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