Predictive values of platinum-related gene polymorphisms in gastric cancer patients on oxaliplatin-based adjuvant chemotherapy

Abstract

To explore the predictive values of platinum-related genes in gastric cancer patients on oxaliplatin-based adjuvant chemotherapy. A total of 126 gastric cancer patients received at least 6 cycles of modified FOLFOX4 adjuvant chemotherapy. Single nuclear polymorphisms (SNPs) in ERCC1 Asp118Asp, XRCC1 Arg399Gln, XPD Lys751Gln and GSTP1 Ile105Val were assessed with 5' nuclease allelic discrimination assay (TaqMan) by real-time polymerase chain reaction and direct sequencing. The genotypes were tested for an association with survivals in gastric cancer patients on an oxaliplatin-based adjuvant chemotherapy regimen. The genotypic analysis of all patients indicated the frequencies for the homozygous wild-type allele, heterozygous and homozygous polymorphic variant: 64.29%, 28.57% and 7.14% for ERCC1-118; 56.35%, 38.89% and 4.76% for XRCC1-399; 84.92%, 15.08% and 0 for XPD-751; and 68.25%, 30.60% and 3.97% for GSTP1-105. Univariate analysis indicated that the ERCC1-118, the XRCC1-399 and the GSTP1-105 SNPs showed the predictive values for RFS (relapse-free survival) (P<0.001, P=0.001 and P<0.001 respectively) and OS (overall survival) (P<0.001, P=0.001 and P=0.019 respectively). A multivariable analysis of Cox proportional hazard regression model suggested that ERCC1-118 had a significant predictive value for RFS (P<0.001, HR=2.362; 95%CI: 1.458-3.827) and OS (P=0.001; HR=2.388; 95%CI: 1.448-3.937) and XRCC1-399 had only a significant predictive value for RFS. And XRCC1-399 (A/A+A/G) genotype could significantly decrease the recurrence risk of patients (P<0.001, HR=0.569; 95%CI: 0.341-0.949). Gastric cancer patients with ERCC1-118 C/C genotype and XRCC1-399A/G or A/A genotype may benefit from an oxaliplatin-based adjuvant chemotherapy.