Abstract
Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide. However, the functional and causal SNPs for CRC remain to be mined. Glucose transporter 1 (GLUT1), a pivotal rate-limiting element in the transport of glucose in malignancy cells, has been identified to be associated with many cancers. Here, we aim to explore the role of GLUT1 in the occurrence and prognosis of colorectal cancer in a Chinese population. We found that GLUT1 expression levels in CRC tumor tissues were significantly higher than those in the corresponding adjacent normal tissues, and Cox multivariate analysis demonstrated that the GLUT1 expression was an independent prognostic factor for CRC (HR = 2.11, 95% CI = 1.33–3.34, P=0.001). For a functional polymorphism of GLUT1 (rs710218), we found that individuals with TT genotype (OR = 1.68, 95% CI = 1.02-2.75, P = 0.041) or AT genotype (OR = 1.47, 95% CI = 1.09-1.99, P = 0.012) of rs710218 had a significantly increased risk of CRC compared to those with AA homozygote. These findings strongly suggest that glucose metabolism related gene GLUT1, and its functional SNP, rs710218 might contribute to CRC susceptibility and prognosis, and the exact biological mechanism awaits further research.
Highlights
Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide [1]
We found that Glucose transporter 1 (GLUT1) expression levels in CRC tumor tissues were significantly higher than those in the corresponding adjacent normal tissues, and Cox multivariate analysis demonstrated that the GLUT1 expression was an independent prognostic factor for CRC (HR = 2.11, 95% confidence interval (CI) = 1.33–3.34, P=0.001)
These findings strongly suggest that glucose metabolism related gene GLUT1, and its functional SNP, rs710218 might contribute to CRC susceptibility and prognosis, and the exact biological mechanism awaits further research
Summary
Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide [1]. According to newly published “Cancer Statistics, 2017” of United States, the estimated new CRC cases were 135,430, and the new deaths were 50,260 in 2017 [2]. The annual CRC cases were 376.3 thousands, while the deaths were 191.0 thousands [3]. CRC has become a major public health problem. It is well established that CRC is a complex trait caused by genetic and environmental factors and their interactions [4,5,6]. Genome-wide association studies (GWASs) have identified numerous susceptibility loci for CRC, most risk variants are located in non-coding regions without clear biological mechanisms [7,8,9,10,11,12,13]. The functional and causal SNPs for CRC remain to be mined
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