Study On The Correlation Between MiR-SNP And The Response Of Chemotherapy In Colon Cancer

OBJECTIVE: The single nucleotide polymorphisms(miR-SNP)sites located on microRNA(miRNA)genes may influence the expression of miRNAs,regulate the expression of drug metabolizing enzymes and / or transporters,and ultimately lead to differences in drug efficacy.In this study,the association of miR-SNP withthe efficacy of capecitabine chemotherapy and the incidence of adverse reactions in advanced colon cancer patients were studied.METHODS: First,the SNP locion the miRNA geneswereobtained from the public database.The genotypes of 20 miR-SNPs in 274 patients with advanced colon cancer were determined by using single base-extension-matrix assisted laser desorption / time-of-flight mass spectrometry.Finally,the correlation between SNP genotypes and the efficacy and adverse reaction of capecitabine chemotherapy in colon cancer patients was statistically analyzed.RESULTS:Firstly,rs744591 and rs745666 were significantly associated with the efficacy of capecitabine combined chemotherapy in colon cancer patients.Compared with rs744591 A/A homozygous patients(effective rate of 33.71%),the efficacy of capecitabine-based chemotherapy in the C/C homozygous patients(48.03%;P = 0.037),the A/C heterozygous patients(53.45%;P = 0.018),and C allele carriers(49.73%;P = 0.013)were significantly higher.When compared with rs745666 G/G homozygous patients,the efficacy of capecitabine-based chemotherapy in the G/C heterozygous patients(35.25% vs 56.25%;P = 0.003)and C allele carriers(39.69% vs 56.25%;P = 0.012)was apparently lower.The efficacy in the rs745666 G/C heterozygous patients was also lower(35.25% vs 54.07%;P = 0.002)than the homozygous patients(G/G and C/C).Secondly,rs2114358,rs35770269 and rs73239138 genotypes were significantly associated with the incidence of adverse reactions in the advanced colon cancer patients received capecitabine-based chemotherapy.The rs2114358 T/C heterozygous patients(OR = 1.876;P = 0.019),the C/C homozygous patients(OR = 2.639;P = 0.038)and the C allele carriers(OR = 2.016;P = 0.005)had a significantly higher risk of adverse reactions,as compared with the T/T homozygous patients.The rs35770269 A/T heterozygous patients(OR = 2.012;P = 0.013),the T/T homozygous patients(OR = 3.759;P = 0.001),and the T allele carriers(OR = 2.299;P = 0.002)also had an obviously higher risk of adverse events than those with A/A genotypes.When compared with the A allele carriers,the risk of adverse events was significantly higher in patients with T/T genotype(OR = 2.404;P = 0.020).The risk of adverse events in the patients with G/A(OR=0.523;P = 0.027),A/A genotype(OR = 0.460;P = 0.021)or A allele(OR = 0.500;P = 0.007)was apparently higher than those with G/G genotype.CONCLUSION:Rs744591 and rs745666 were significantly associated with chemotherapy efficacy in the advanced colon cancer patients treated with capecitabine.Rs2114358,rs35770269 and rs73239138 were significantly associated with the risk of adverse reactions in these patients.This is of potential value in predicting the efficacy and side effects of capecitabine chemotherapy in advanced colon cancer patients.