title: Genetic polymorphisms in the MMP-7 gene and breast cancer survival.
abstract: 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.
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Beeghly-Fadiel
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
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