The value of XPD and XRCC1 genotype polymorphisms to predict clinical outcome in metastatic colorectal carcinoma patients with irinotecan-based regimens

Abstract

Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC). We prospectively treated 43 MCRC patients with irinotecan-based regimens (XELIRI or IFL). Allelic variants of the XRCC1 gene at codon 399 and XPD gene at codon 751 were analyzed in lymphocyte DNA by PCR-RFLP. Clinical outcome variables: overall survival (OAS), progression-free survival (PFS) and the occurrence of grade 3 or 4 hematological and gastrointestinal (GIS) toxicities were evaluated. In the univariate analysis for OAS (n = 43) only XPD and XRCC1 polymorphisms were significant (P = 0.05 and P = 0.04, respectively). After adjustment for performance status (ECOG = 0, 1 vs. 2) and disease extent (single vs. multiple metastatic site), XRCC1 genotype and performance status retained significance (HR = 2.85, P = 0.04, and HR = 3.19, P = 0.02, respectively). Gln/Gln genotype was associated with the greatest risk of death. Type of presentation (metastatic vs. local disease at first presentation) was the only significant predictor of PFS in the univariate analysis (n = 40, P = 0.003). After adjustment for performance status and disease extent, type of presentation retained its significance (HR = 4.35, P = 0.003). None of the toxicities was associated with these genotypes. XRCC1 genotype independently predicted overall survival in metastatic colorectal carcinoma patients treated with irinotecan-based chemotherapy.