Pharmacogenetic studies in rectal cancer patients treated with preoperative chemoradiotherapy.

14645 Background: Chemotherapy using 5-FU is known to be effective in the treatment of rectal cancer patients and more recently Oxaliplatin (OXA) has been added to preoperative FU-based pelvic chemoradiation. We report the study of polymorphisms in the TS, GSTP1 and different repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 82 rectal cancer patients treated with preoperative chemoradiotherapy Methods: Radiation therapy was administered to all patients. 5-FU was administered alone in 38 patients and in combination with OXA in additional 44 patients. Genetic polymorphisms were determined by Real-Time PCR. The investigated polymorphisms were: TS (VNTR/ 5' UTR, 3R G>C SNP, 1494del6), ERCC1 (Asn118Asn, 8092C>A, 19716 G>C), GSTP1 (Ile105Val), XRCC1 (Arg194Trp, Arg280His, Arg399Gln) and XPD (Lys751Gln). Pathological response, progression free survival and overall survival were evaluated according to each genotype.,Although no significant association was observed for pathological remission, a trend to a better response was seen in patients carriyng a G/G genotype for the 3'UTR SNP in the ERCC1 gene (44% of the G/G achieved a complete pathological response or a microfoci residual tumour, while 26% of G/T-T/T patients responded P= 0.07). Any of the markers analyzed showed a statistical significant relationship with PFS. If we considered only the group of patients treated with the 5-FU/OXA regimen, a significantly different PFS was observed according to the genotype of the Arg399Gln polymorphism in the XRCC1 genes (50 months for G/G patients, 39 months for G/A patients and 20 months for A/A patients; P=0.05). The univariate analysis showed that any of the molecular markers studies were of predictive value for overall survival.,No clear associations between these genetic markers and the clinical outcome can be defined in local advanced rectal cancer patients treated with preoperative chemoradiotherapy. No significant financial relationships to disclose.