Association of matrix metalloproteinase-8 gene variation with breast cancer prognosis

Julie Decock, Ji Rong Long, Ross C. Laxton, Xiao Ou Shu, Conrad Hodgkinson, Wouter Hendrickx, Eve G. Pearce, Yu Tang Gao, Andresa C. Pereira, Robert Paridaens, Wei Zheng, Shu Ye

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Animal and cell studies indicate an inhibitory effect of matrix metalloproteinase-8 (MMP8) on tumorigenesis and metastasis. We investigated whether MMP8 gene variation was associated with breast cancer metastasis and prognosis in humans. We first studied nine tagging single nucleotide polymorphisms (SNP) 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 ∼ 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 tumor-node-metastasis stage 0 to II, the adjusted hazard ratio of disease-free survival was 0.7 [95% confidence interval (95% CI), 0.5-0.9] 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.

Original languageEnglish
Pages (from-to)10214-10221
Number of pages8
JournalCancer Research
Issue number21
Publication statusPublished - 1 Nov 2007


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Decock, J., Long, J. R., Laxton, R. C., Shu, X. O., Hodgkinson, C., Hendrickx, W., Pearce, E. G., Gao, Y. T., Pereira, A. C., Paridaens, R., Zheng, W., & Ye, S. (2007). Association of matrix metalloproteinase-8 gene variation with breast cancer prognosis. Cancer Research, 67(21), 10214-10221.