Abstract
The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA) may modulate the posttranscriptional regulation of gene expression and explain individual sensitivity to chemotherapy. Here we investigated the correlation between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based chemotherapy in 274 advanced colon cancer patients. Statistical analysis indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C allele (49.73%) responded to the chemotherapy than those with the A/A genotype (33.71%). The response rates of rs745666 G/C heterozygous patients (35.25%) and C allele carriers (39.69%) were apparently less than that of the G/G homozygous patients (56.25%). Moreover, three SNPs rs2114358, rs35770269, and rs73239138 were significantly associated with the occurrence of side effects of chemotherapy. The patients with rs2114358 C allele (OR = 2.016) or rs35770269 T allele (OR = 2.299) were much more prone to endure adverse events. However, the incidence of side effect was lower in the patients carrying rs73239138 A allele than those with G/G genotype (OR = 0.500). Our findings demonstrate that genetic variations in pre-miRNA may influence the efficacy of capecitabine-based chemotherapy in advanced colon cancer patients.
Highlights
Colorectal carcinoma (CRC), including colon cancer and rectal cancer, is one of the most common gastrointestinal malignancies
Our findings demonstrate that genetic variations in premiRNA may influence the efficacy of capecitabine-based chemotherapy in advanced colon cancer patients
The results demonstrate that two polymorphisms are significantly related to the efficacy and three loci contribute to the occurrence of adverse events of chemotherapy
Summary
Colorectal carcinoma (CRC), including colon cancer and rectal cancer, is one of the most common gastrointestinal malignancies. Due to the heterogeneity of cancer www.impactjournals.com/oncotarget cells, the cell sensitivity to chemotherapy drugs is quite different, which leads to significant individual response and occurrence of adverse events in patients [5]. Several studies have shown that the miRNA-related SNPs are related to the efficacy and/or occurrence of adverse events of capecitabine-based chemotherapy for CRC patients [10, 11]. Meulendijks et al have shown that polymorphisms in the miR-27a genomic region (MIR27A) can be used to improve the predictive value of DPYD variants to identify the risk of severe fluoropyrimidine associated toxicity in cancer patients. The results demonstrate that two polymorphisms are significantly related to the efficacy and three loci contribute to the occurrence of adverse events of chemotherapy
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