Polymorphisms of monocarboxylate transporter genes are associated with clinical outcomes in patients with colorectal cancer.

Abstract

Previous studies have demonstrated that monocarboxylate transporters (MCTs) play important roles in the development and progression of many cancers. The purpose of this study was to assess the effects of single-nucleotide polymorphisms (SNPs) of MCT genes on prognosis of colorectal cancer (CRC) patients. Nine functional SNPs in three MCT genes (MCT1, MCT2 and MCT4) were selected and genotyped using Sequenom iPLEX genotyping system in 697 Chinese CRC patients receiving surgery. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognostic analysis. One SNP (MCT1: rs1049434/exon) was significantly associated with overall survival of CRC patients (HR 0.74; P = 0.046). Two other SNPs (MCT1: rs60844753/5' near gene and MCT2: rs995343/intron) exhibited associations with recurrence-free survival of CRC patients (HR 0.67; P = 0.078 and HR 0.74; P = 0.036, respectively). Our study also showed that MCT1 rs1049434, rs60844753 and MCT2 rs995343 SNPs had a cumulative effect on CRC recurrence-free survival (P for trend 0.011). Those who carrying three unfavorable genotypes (WW for all SNPs) had a 2.06-fold increased risk of recurrence compared with patients carrying no unfavorable genotypes (P = 0.016). Moreover, we found that patients carrying no <2 risk genotypes showed significant OS and RFS benefits from adjuvant chemotherapy. Our findings suggest that SNPs in MCT1 and MCT2 genes may affect clinical outcomes and can be used to predict the response to adjuvant chemotherapy in CRC patients who received surgical treatment once validated in future study.