ERCC5 promoter polymorphisms at –763 and +25 predict the response to oxaliplatin-based chemotherapy in patients with advanced colorectal cancer

Abstract

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This study aimed to investigate whether single nucleotide polymorphisms (SNPs) in the

promoter of the excision repair cross complementation group 5 (ERCC5) gene influences

response to oxaliplatin-based chemotherapy. Eighty-three patients with cytologically or

histologically confirmed advanced colorectal cancer (CRC), at least one measurable lesion

and underwent oxaliplatin-based chemotherapy were studied. To this end, six polymorphisms

(-1415C>T, -763A>G, -413C>T, +25A>G, +202C>T, +372C>T) in the ERCC5 promoter were

selected for investigation. Genomic DNA was obtained from peripheral blood cells, and

polymerase chain reaction-ligation detection reaction was used to analyze these SNPs. The

χ2 test or Fisher’s exact test was then used to investigate the association between

polymorphisms and chemotherapy response. Our results showed that the response rate

among patients with the -763GG genotype (72.7%) was significantly higher than that of other

genotypes (22.2% for AA genotype, P=0.008 and 37.2% for AG genotype, P=0.046

respectively). In addition, the response rate among patients with the +25AA genotype (75%)

was significantly higher than that of other genotypes (24.1% for GG genotype, P=0.004 and

35.7% for AG genotype, P=0.022 respectively). Patients with the -763A/+25G haplotype had

a higher risk of non-response to oxaliplatin chemotherapy compared to those carrying the

-763G/+25A haplotype (OR 2.672, 95% CI 1.353-5.278, P=0.004). However, no genetic

variation was observed at site -413, and no significant association was found between the

-1415C>T, +202C>T or +372C>T polymorphisms and chemotherapy response. Therefore,

these data suggest that ERCC5 promoter polymorphisms at -763 and +25 may be important

predictors of response to oxaliplatin chemotherapy.