Abstract
N6-methyladenosine (m6A) modification plays a vital regulatory role in tumorigenesis and development. In this study, we determined that the mRNA expression of IGF2BP1, IGF2BP2 and IGF2BP3, as the m6A modification genes, was significantly increased in gastric cancer (GC) tissues. Using a logistic regression model, we found that novel single-nucleotide polymorphism (SNP) rs9906944 C > T in IGF2BP1 was remarkably associated with a decreased risk of GC in discovery stage (odds ratio (OR) = 0.75, 95% confidence interval (95% CI): 0.60–0.93, P = 8.51 × 10−3). This finding was repeated in an independent Nanjing population (OR = 0.76, 95% CI: 0.59–0.98, P = 3.45 × 10−2). The combined analysis including 2900 GC cases and 3,536 controls confirmed the association between rs9906944 C > T and GC risk (OR = 0.75, 95% CI: 0.64–0.88, P = 5.76 × 10−4). Furthermore, we found that GC patients with higher IGF2BP1 mRNA expression level had prominent poorer overall survival (hazard ratio (HR) = 1.49, 95% CI: 1.16–1.91, logrank P = 1.50 × 10−3). For the first time, our findings suggested the importance of genetic variants in m6A regulators in GC and indicated that IGF2BP1 plays a crucial role in GC. Genetic variants in m6A modification genes may be used for GC risk prediction.
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Acknowledgements
We thank Dr. Meilin Wang for his kind help in this study. This study was partly supported by the National Key R&D Program of China (Grants 2018YFC1313100, 2018YFC1313102) and National Natural Science Foundation of China (81773539). Collaborative Innovation Center for Cancer Personalized Medicine, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).
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ZD Z, HY C and J Q designed and supervised this study; XW W, D G and DF W carried out the experimental work, conducted the data analysis and wrote this manuscript; HT L and WD G helped collect samples; YL W and ML D revised this manuscript.
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Wang, X., Guan, D., Wang, D. et al. Genetic variants in m6A regulators are associated with gastric cancer risk. Arch Toxicol 95, 1081–1088 (2021). https://doi.org/10.1007/s00204-020-02958-1
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DOI: https://doi.org/10.1007/s00204-020-02958-1