The Association Of MiR-SNP With The Occurrence, Development, And Chemotherapeutic Response Of Colorectal Cancer

Objective: To study the correlation between genotypes of miR-SNP and the occurrence, development, and chemotherapeutic response of colorectal cancer(CRC).Method: Firstly, the single nucleotide polymorphisms(SNPs) in mature microRNAs were selected from the online databases. Secondly, genomic DNAs were extracted from the peripheral blood of the health controls and CRC patients. Then, the DNA fragments containing the SNPs were amplified by PCR method. Thirdly, the SNP genotypes were detected by using single base extension combined with matrix assisted laser desorption ionization-time of flight-mass spectrometry(MALDI-TOF-MS) method. Lastly, the correlation between genotypes of miR-SNP and occurrence, development, and chemotherapeutic response of CRC was analyzed.Results:(1) We found that the distribution of rs61992671 genotypes was statistically significant different between the healthy controls and colorectal cancer patients(P<0.05). Compared to A/A genotype, the A/G genotype(OR=1.77, 95% CI=0.98-3.20) was less frequent in CRC patients. However, we had not found obvious correlation between the genotypes of rs12402181 and rs67106263(P>0.05) and the risk of CRC.(2) We found that rs12402181 genotypes were significantly related to tumor size and tumor type(P<0.05). As compared to G/G genotype, the G/A-A/A genotype(OR = 1.67, 95% CI=1.00-2.78) in the dominant model had a higher risk of big tumor size; in comparison to G/G-A/A genotype, the G/A genotype(OR=0.69, 95% CI=0.47-1.00) in the overdominant model had a higher risk of colon cancer. There were statistically significant differences between rs67106263 genotype and the degree of differentiation. In comparison to G/G genotype, the G/A genotype(OR=2.35,95%CI=1.27-4.35) in the codominant model had a higher risk of low degree of differentiation; in comparison to G/G genotype, the G/A-A/A genotype(OR=2.38,95%CI=1.31-4.33) in the dominant model had a higher risk of low degree of differentiation; in comparison to G/G-A/A genotype, the G/A genotype(OR=2.26,95%CI=1.23-4.26) in the overdominant model had a higher risk of low degree of differentiation.(3) rs12402181 was nearly related to the side effect of capecitabine chemotherapy(P=0.056) in the recessive model: in comparison to G/G-G/A genotype, the A/A genotype(OR=0.38, 95%CI=0.14-1.04) had a less risk of adverse reaction; rs12402181 was nearly related to the side effect of 5-FU chemotherapy(P=0.072) in the overdominant model: in comparison to G/G-A/A genotype, the G/A genotype(OR=2.07, 95%CI=0.93-4.59) had a higher risk of adverse reaction; rs12402181 was nearly related to the side effect of oxaliplatin chemotherapy(P=0.088) in the recessive model: in comparison to G/G-G/A genotype, the A/A genotype(OR=0.49,95%CI=0.22-1.12) had a less risk of adverse reaction.(4) We found that there were statistically significant correlation between rs61992671 genotypes and the effect of 5-FU and oxaliplatin chemotherapy(P<0.05).Conclusion:(1) The SNP rs61992671 was significantly related to the occurrence of colorectal cancer and the effect of chemotherapy.(2) The SNP rs12402181 and rs67106263 were significantly related to the development of colorectal cancer.(3) SNP rs12402181 was likely related to the side effect of chemotherapy.