Tissue factor promoter polymorphism as a prognostic factor in patients with metastatic colon cancer

Abstract

4108 Background: Tissue Factor (TF), a transmembrane glycoprotein, initiates the physiologic coagulation cascade. Cumulative evidence implies that TF plays a key role in tumor angiogenesis. Elevated TF expression has been reported to be associated with poor survival in patients in solid tumor. We investigated whether a functional TF promoter polymorphism -603 A/G is a prognostic factor in patients with advanced colon cancer because the G allele had been linked to high constitutive TF gene expression in human monocytes in healthy volunteers. Methods: 318 patients with metastatic colon cancer treated at the USC/Norris Comprehensive Cancer Center or the LA County/USC Medical Center during 1992 through 2003 were included in this study. Genomic DNA was extracted from white blood cells of peripheral blood samples using the QiaAmp kit (Qiagen, Valencia, CA). The TF polymorphism was genotyped by PCR-RFLP-based approach. The association between the TF polymorphism and overall survival was examined using the log-rank and trend test. The association between TF polymorphism and baseline demographic characteristics was tested using the χ2 test or Fisher’s exact test when appropriate. Results: There were 141 females and 177 males, with a median age of 58 years (range 25–86). The cohort comprised 234 whites, 43 Asians, 15 Blacks, 24 Hispanics, and 2 Native Americans. The median survival was 13.7 months with a median follow-up of 2.3 years. Asians were less likely to bear the G allele compared to other racial groups (P < 0.001, Fisher’s exact test). Patients who carried 1 or 2 G alleles were at higher risk of poor survival compared to patients with no G alleles (A/A) (P = 0.038, trend test). The median overall survival was 14.7 vs. 11.9 months for patients with A/A vs. patients with G/G or A/G, respectively. Conclusions: This study suggests that TF may be a prognostic factor for patients with metastatic colon cancer. The finding should be validated with future prospective clinical studies. No significant financial relationships to disclose.