Genetic polymorphisms in the MMP-7 gene and breast cancer survival.

Beeghly-Fadiel A, Shu XO, Long J, Li C, Cai Q, Cai H, Gao YT, Zheng W
Int J Cancer. 2009 124 (1): 208-14

PMID: 18798254 · PMCID: PMC2597698 · DOI:10.1002/ijc.23859

Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression has been shown to be associated with tumor invasion, metastasis and survival for a variety of cancers. We systematically evaluated single nucleotide polymorphisms (SNPs) in MMP-7 in relation to breast cancer survival in a large follow-up study. Included were 1,079 breast cancer cases that were recruited from 1996 to 1998 and followed for a median of 7.1 years as part of the Shanghai Breast Cancer Study (SBCS). Eleven SNPs, including 2 known functional promoter SNPs, were analyzed using the Affymetrix Targeted Genotyping System. Associations with survival were evaluated by Cox proportional hazards regression and Kaplan-Meier functions. Statistically significant associations with disease-free and/or overall survival (OS) were found for 5 polymorphisms; these associations were explained primarily by 2 SNPs (rs11568818 and rs11225297) that were in high linkage disequilibrium (LD) with the others. Patients homozygous for the rs11568818 rare allele (G) had a significantly worse prognosis (OS HR: 6.7, 95% CI: 2.4-18.6) than patients homozygous for the common allele (A). Significantly improved survival was seen for patients with the rs11225297 T allele, and this association occurred in a dose-response manner; patients with AT (OS HR: 0.7, 95% CI: 0.5-0.9) and TT (OS HR: 0.3, 95% CI: 0.1-0.8) fared better than patients with AA (p-value for trend: 0.001). Thus, common MMP-7 genetic polymorphisms were found to be significant determinants of survival among Chinese women with breast cancer.

MeSH Terms (15)

Adult Alleles Breast Neoplasms Disease-Free Survival Female Humans Linkage Disequilibrium Matrix Metalloproteinase 7 Middle Aged Neoplasm Metastasis Polymorphism, Genetic Polymorphism, Single Nucleotide Prognosis Proportional Hazards Models Treatment Outcome

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