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.