Influence of ABCB-1, ERCC-1 and ERCC-2 gene polymorphisms on response to capecitabine and oxaliplatin (CAPOX) treatment in colorectal cancer (CRC) patients of South India.

Abstract

High interindividual response variability was reported with capecitabine and oxaliplatin (CAPOX) regimen in colorectal cancer (CRC). The single nucleotide polymorphisms (SNPs) of the genes related to drug efflux transport (ABCB1) and DNA repair (ERCC) could result in altered tumour response. Hence, this study was designed to assess the influence of ABCB1, ERCC-1 and ERCC-2 gene polymorphisms on tumour response to CAPOX treatment in CRC patients of South Indian origin. A total of 145 newly diagnosed CRC patients were included in the final analysis. Response to CAPOX treatment in the adjuvant setting was assessed in terms of disease-free survival rate (DFSR) and overall survival rate (OSR) at 3years, whereas in the palliative setting, the response was assessed as progression-free survival rate (PFSR) and OSR at 3years. Five millilitres of the venous blood sample was collected from each patient for genomic DNA extraction by the manual phenol-chloroform method. Genotyping and allelic discrimination analysis were done using real-time PCR (RT-PCR). With ABCB1 gene polymorphism rs1045642 (A>G), patients with AG/GG genotype showed better DFSR [P value=.02, OR=2 (CI: 1.5-3)] and PFSR [P value=.02, OR=1.6 (CI: 1.1-2.5)] when compared to AA genotype in the adjuvant and palliative settings, respectively. Similarly with rs1128503 (A>G) polymorphism, patients with AG/GG genotype were found to have better DFSR [P value=.02, OR=1.9 (CI: 1.3-3)] and PFSR [P value=.01, OR=2 (CI: 1.1-3.7)] when compared to AA genotype. However, we did not find any association between CAPOX response and ABCB1 gene polymorphisms in a binary logistic regression when non-genetic predictors were considered for analysis. We did not find any association with ERCC1 (rs11615 A>G) and ERCC2 (rs13181 T>G) gene polymorphisms with respect to CAPOX response in either of the treatment settings. The response to CAPOX treatment was found to be influenced by the ABCB1 gene variants (rs1128503 and rs1045642), thereby strengthening their predictive role. No association was found between ERCC1 (rs11615 A>G), ERCC2 (rs13181 T>G) gene polymorphisms and tumour response to CAPOX treatment in CRC patients of South Indian origin.