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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-10-11

AUTHORS

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

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. More... »

PAGES

61-69

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-006-9345-2

DOI

http://dx.doi.org/10.1007/s10549-006-9345-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044310400

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17033924


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77 heterozygotes
78 homozygosity
79 homozygotes
80 importance
81 inhibitors
82 large case-control study
83 matrix metalloproteinases
84 metalloproteinases
85 multiple comparisons
86 nucleotide polymorphisms
87 polymorphism
88 progesterone receptor status
89 progression
90 promoter polymorphism
91 promoter region
92 rarity
93 receptor status
94 region
95 risk
96 series
97 single nucleotide polymorphisms
98 status
99 study
100 survival
101 survival analysis
102 susceptibility
103 tumor progression
104 usefulness
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