Dataset Information

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.

SUBMITTER: Beeghly-Fadiel A

PROVIDER: S-EPMC2597698 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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

Beeghly-Fadiel Alicia A Shu Xiao-Ou XO Long Jirong J Li Chun C Cai Qiuyin Q Cai Hui H Gao Yu-Tang YT Zheng Wei W

International journal of cancer 20090101 1

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 ...[more]

PMID: 18798254

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Project description:Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.

Dataset Information

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

Publications

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

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