Volume 10 Supplement 2

Breast Cancer Research 2008

Open Access

Association of MMP8 gene variation with breast cancer prognosis

  • J Decock1, 2,
  • JR Long3,
  • RC Laxton4, 5,
  • XO Shu3,
  • C Hodgkinson4,
  • W Hendrickx1,
  • EG Pearce5,
  • YT Gao6,
  • AC Pereira7,
  • R Paridaens1,
  • W Zheng3 and
  • S Ye4, 5
Breast Cancer Research200810(Suppl 2):P32

https://doi.org/10.1186/bcr1916

Published: 13 May 2008

Animal and cell line studies indicate an inhibitory effect of matrix metalloproteinase 8 (MMP8) on tumorigenesis and metastasis [13]. We investigated whether MMP8 gene variation was associated with breast cancer metastasis and prognosis in humans. We first studied nine tagging single nucleotide polymorphisms (SNPs) in the MMP8 gene in 140 clinically and pathologically well-characterized breast cancer patients. Four of the SNPs were found to be associated with lymph node metastasis, the most pronounced being a promoter SNP (rs11225395) with its minor allele (T) associating with reduced susceptibility to lymph node metastasis (P = 0.02). This SNP was further evaluated for association with cancer relapse and survival among a cohort of approximately 1,100 breast cancer patients who had been followed for cancer recurrence and mortality for a median of 7.1 years. The T allele was associated with reduced cancer relapse and greater survival, particularly among patients with earlier stage cancer. Among patients of tumour-node-metastasis stage 0-II, the adjusted hazard ratio of disease-free survival was 0.7 (95% CI, 0.5 to 0.9) for patients carrying T allele compared with those homozygous for the C allele (P = 0.02). In vitro experiments showed that the T allele had higher promoter activity than the C allele in breast cancer cells. Electrophoretic mobility shift assays showed binding of nuclear proteins to the DNA sequence at the SNP site of the T allele but not that of the C allele. The data suggest that MMP8 gene variation may influence breast cancer prognosis and support the notion that MMP8 has an inhibitory effect on cancer metastasis.

Declarations

Acknowledgements

Supported by the EU Cancerdegradome Project (LSHC-CT-2003-503297), and research grants (R01CA64227 and R01CA090899) from the National Cancer Institute and CAPES/BRAZIL (PDEE 2730/05-7). The data in this abstract are presented in a manuscript accepted for publication in Cancer Research.

Authors’ Affiliations

(1)
Laboratory for Experimental Oncology
(2)
Biomedical Research Centre, School of Biological Sciences, University of East Anglia
(3)
Department of Medicine, Vanderbilt Epidemiology and Cancer Centre, Vanderbilt University School of Medicine
(4)
William Harvey Research Institute, Barts and The London School of Medicine
(5)
Human Genetics Division, University of Southampton
(6)
Department of Epidemiology, Shanghai Cancer Institute
(7)
Departamento de Biociencias e Diagnostico Bucal, Faculdade de Odontologia de São José dos Campos – UNESP

References

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Copyright

© BioMed Central Ltd 2008

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