AB91. Study on association of single nucleotide polymorphisms and chemotherapy sensitivity in advanced gastric cancer

Purpose: To investigate whether single nucleotide polymorphisms within genes known or suspected to influence drug activity could predict the efficacy of FOLFOX-4 regimens in patients with advanced gastric cancer.

Methods: 186 advanced gastric cancer patients who received FOLFOX-4 adjuvant chemotherapy were enrolled in this study. Peripheral blood samples were used for genotyping 6 polymorphisms in XRCC1-399, XPD-751, ERCC1-118, GSTP1-105, TSER and TS-3’UTR. The primary end point was to investigate the association between genotypes and progression-free survival (PFS).

Results: The mPFS was 9.0 months in patients with XRCC1-399 G/G genotype, which was 2.5 months higher than those with other genotypes (P=0.039). Patients with GSTP1-105 G/G genotype had a longer mPFS than those with other genotypes (9 vs. 7.5 months, P=0.018). Patients with TS-3'UTR 6bp^-/6bp^- genotype had a longer mPFS than those with other genotypes (10 vs. 7.5 months, P=0.041). Patients with more than 3 favorable alleles had a longer mPFS than those with no more than 3 favorable alleles (11.5 vs. 7 months, P=0.008). Only the number of the favorable alleles revealed prognostic values for PFS on multivariate analysis (P=0.033, HR=0.411)

Conclusions: XRCC1-399 G allele, GSTP1-105 G allele and TS-3’UTR 6bp^- allele can improve the PFS of patients treated with FOLFOX, respectively. Additionally, the number of the favorable alleles of XRCC1 -399, GSTP1-105 and TS- 3’UTR can be identified as a predictor for FOLFOX regimen. It may play roles in predicting therapeutic effects as well as in tailoring medication for advanced gastric cancers.

Keywords: Gastric cancer; single nucleotide polymorphisms; FOLFOX; XRCC1; XPD; ERCC1; GSTP1; TS