Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):9973-9980. doi: 10.26355/eurrev_202010_23210.
OBJECTIVE: The aim of this study was to investigate the correlations of UDP glucuronosyltransferase family 1 member A1 (UGT1A1) gene polymorphisms with the onset and prognosis of non-small cell lung cancer.
PATIENTS AND METHODS: A total of 400 patients with non-small cell lung cancer (disease group) and healthy controls (control group) in our hospital were selected as research subjects. Genomic DNA was extracted from the peripheral blood. UGT1A1 gene polymorphisms rs8330, rs4148323 and rs35003977 were detected after Polymerase Chain Reaction (PCR) amplification. RT-qPCR was performed to measure the expression level of UGT1A1. The survival of patients was analyzed combined with their prognosis. Moreover, the expression of UGT1A1 gene in lung cancer patients from The Cancer Genome Atlas (TCGA) database was analyzed by bioinformatics, and the prognosis was analyzed.
RESULTS: According to the expression level of UGT1A1 gene from TCGA and GTEx databases, UGT1A1 gene was highly expressed in lung cancer tissues but lowly expressed in normal lung tissues, and the difference was statistically significant (p<0.05). Combined with the expression level of UGT1A1 and the prognostic information of lung cancer patients from TCGA database, patients with higher expression level of UGT1A1 gene exhibited significantly better prognosis than those with lower level (p=0.0013), suggesting that UGT1A1 gene is an anti-oncogene. There were statistically differences in allele distribution of UGT1A1 gene polymorphism rs8330 between the disease group and control group (p=0.003), and the frequency of allele G was higher in disease group. Moreover, the distribution of genotypes of UGT1A1 gene polymorphisms rs8330 (p=0.006) and rs4148323 (p=0.003) in the disease group was significantly different from that in the control group, and the frequencies of GG genotype of polymorphisms rs8330 and rs4148323 were higher in the disease group. Statistically significant differences in the distribution of recessive models of UGT1A1 gene polymorphism rs8330 were observed between the disease group and control group (p=0.047), and the disease group exhibited a lower frequency of recessive model GC + CC than control group. There were evident differences in the distribution of haplotype GGT of UGT1A1 gene polymorphisms rs8330, rs4148323 and rs35003977 between the disease group and control group (p=0.004), and the frequencies of haplotype GGT were higher in the disease group than those in the control group. UGT1A1 gene polymorphism rs8330 was remarkably associated with gene expression (p<0.05). Meanwhile, the expression of UGT1A1 gene in patients carrying genotype CC declined notably compared with that in patients carrying genotypes GG and GC (p<0.05). Furthermore, the polymorphism rs8330 had a significant correlation with the survival of patients in disease group (p=0.0001), and patients with genotype CC had the worst prognosis.
CONCLUSIONS: UGT1A1 gene polymorphisms are prominently correlated with the onset and prognosis of non-small cell lung cancer.