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Functional Plasminogen Activator Inhibitor-1 Gene Variants and Breast Cancer Survival

Authors' Affiliations: ¹ Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee and ² Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

Requests for reprints: Xiao-Ou Shu, Department of Medicine, Center for Health Services Research, Vanderbilt University, Medical Center East, Suite 6000, 1215 21st Avenue South, Nashville, TN 37232-8300. Phone: 615-936-0713; Fax: 615-936-1269; E-mail: Xiao-Ou.Shu{at}Vanderbilt.edu.

Purpose: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in cancer invasion and metastasis. A common polymorphism (4G/5G) in the promoter region of the PAI-1 gene has been reported to influence transcription and plasma levels of PAI-1. We evaluated the association between PAI-1 4G/5G polymorphism and breast cancer survival in a population-based cohort of breast cancer patients.

Experimental Design: Included in this analysis were 1,083 Chinese women diagnosed with stage 0 to III primary breast cancer at age 25 to 64 years who were recruited between 1996 and 1998 for the Shanghai Breast Cancer Study and followed for a median of 5.2 years. The Kaplan-Meier method and Cox model were used to evaluate the genotype and survival association.

Results: After adjustment for known prognostic factors for breast cancer, patients homozygous for the 4G allele had significantly poorer disease-free survival [hazard ratio (HR), 1.7; 95% confidence interval (95% CI), 1.1-2.4] and overall survival (HR, 1.5; 95% CI, 1.0-2.3) than those homozygous for the 5G allele. The association was more evident in patients with advanced disease. The HRs (95% CI) were 3.5 (1.4-9.0) for disease-free survival and 3.1 (1.1-8.3) for overall survival in stage III patients.

Conclusions: The PAI-1 4G/5G polymorphism may be a prognostic marker for young and middle-aged Chinese breast cancer patients.

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