Basal sFAS/sFASL ratio and FAS polymorphisms, as a prognostic marker, in advanced colorectal carcinoma patients (ACRC), treated with oxaliplatin-based chemotherapy

Abstract

3631 Background: FAS (CD95) has been implicated in DNA-damage sensitivity. We have previously shown that decrease of sFAS/sFASL ratio correlates with acquired chemotherapy-resistance (Nadal et al. Proc. ASCO 2004). We analyzed now the influence of basal sFAS/sFASL ratio and FAS gene polymorphisms in the promoter region, on survival. Methods: Eligible criteria included; patients with ACRC and ECOG performance status (PS) 0–2, treated with first-line oxaliplatin-based chemotherapy. A maximum of 6 months of therapy was planned. CT scans were done every 3 months until progressive disease. ELISA sFAS and sFASL analysis were done before therapy. FAS -1377 and -670 gene polymorphism was tested using PCR-RFLP method in genomic DNA extracted from peripheral blood. Results: From July 2001 to September 2003, 67 patients were included. Median age 63 (33–80), 61% male, 81% ECOG (PS) 0–1. With a median follow-up of 26 months, median progression free survival was 9 months and median survival time was 20 months. Median basal sFAS/sFASL ratio was 80.8 ng/ml. We found a significant association between sFAS/sFASL ratio and survival. Patients with ratio ≥80.8 ng/ml survived a median time of 13 months (95% CI 10–16) compared with 30 months (95% CI 17–42) of patients with ratio <80.8 ng/ml (p=0.002). We didn’t found a significant association between FAS -670 gene polymorphism and survival. Patients with GG homozygous genotype survived a median of 22 months (95% CI 13–32), compared with, those have homozygous AA genotype 20 months (95% CI 11–28) or heterozygous GA genotype 19 months (95% CI 4–33), respectively (p=0.84). ECOG PS (p=0.0007) but not serum LDH concentration level (>1UNL) (p=0.23) was also significant predictors for survival. Conclusion: These data suggest that high basal sFAS/sFASL ratio could identify a group of ACRC patients with poorer prognosis. No significant financial relationships to disclose.