Abstract
Vitamin E is effective for preventing the risk of cancer. However, few studies have elucidated the mechanism of vitamin E in cancer occurrence. Herein, we aimed to identify the genetic variants in vitamin E-related pathway genes associated with colorectal cancer risk. We applied logistic regression models to assess the association between single-nucleotide polymorphisms (SNPs) in vitamin E-related pathway genes and colorectal cancer risk in the Chinese and European population. The false discovery rate (FDR) method was used to correct multiple comparisons. The mRNA and protein expression analysis were evaluated in public database and in-house RNA-Seq data. SCARB1 rs73227586 was identified significantly increased risk of colorectal cancer in the Chinese population (odd ratio (OR) = 1.46, 95% confidence interval (CI) = 1.22–1.75, P = 2.99 × 10–5). This finding was further validated in the European population (OR = 1.11, 95% CI = 1.02–1.20, P = 1.44 × 10–2). Additionally, the mRNA and protein expression of SCARB1 were markedly up-regulated in colorectal tumor tissues. Moreover, rs73227586 T allele could increase the minimum free energy (MFE) and weaken binding ability to transcription factor ELL2. Our findings indicated that SCARB1 may play a carcinogenic role in colorectal cancer. Genetic variants in vitamin E-related pathway genes may concern to be predictors of colorectal cancer risk.
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Abbreviations
- SNP:
-
Single-nucleotide polymorphism
- OR:
-
Odds ratio
- CI:
-
Confidence interval
- MAF:
-
Minor allele frequency
- HWE:
-
Hardy–Weinberg equilibrium
- LD:
-
Linkage disequilibrium
- FDR:
-
False discovery rate
- eQTL:
-
Expression quantitative trait loci
- GWAS:
-
Genome-wide association study
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Funding
This study was supported by the National Natural Science Foundation of China (81822039 and 81872697), the Qinlan Project of Jiangsu (M.W.), Six Talent Peaks Project of Jiangsu Province (YY‐020) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).
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Meilin Wang conceived and designed the experiments. Mulong Du, Shuwei Li and Junyi Xin contributed reagents/materials/analysis tools. Qiuyi Zhang and Yixuan Meng wrote the paper. Zhengdong Zhang, Dongying Gu and Shuai Ben revised the paper. All authors reviewed the manuscript.
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Zhang, Q., Meng, Y., Du, M. et al. Evaluation of common genetic variants in vitamin E-related pathway genes and colorectal cancer susceptibility. Arch Toxicol 95, 2523–2532 (2021). https://doi.org/10.1007/s00204-021-03078-0
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DOI: https://doi.org/10.1007/s00204-021-03078-0