Progress on functional mechanisms of colorectal cancer causal SNPs in post-GWAS
Li Yige,1,2,3, Zhang Dandan,1,2,31 Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310058, China 2 Department of Medical Oncology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China 3 Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou 310058, China;
the National Natural Science Foundation of China.81773027 the National Natural Science Foundation of China.81101640 Natural Science Foundation of Zhejiang Province of China.LY21H160027 Fundamental Research Funds for the Central Universities
PDF (659KB)元数据多维度评价相关文章导出EndNote|Ris|Bibtex收藏本文 本文引用格式 李以格, 张丹丹. 后GWAS时代结直肠癌致病SNP功能机制的研究进展. 遗传[J], 2021, 43(3): 203-214 doi:10.16288/j.yczz.20-320 Li Yige. Progress on functional mechanisms of colorectal cancer causal SNPs in post-GWAS. Hereditas(Beijing)[J], 2021, 43(3): 203-214 doi:10.16288/j.yczz.20-320
结直肠癌(colorectal cancer, CRC)是常见的恶性肿瘤之一,严重威胁人类健康。据统计,2018年全球CRC新发病例超过180万,死亡病例约86万;位居发病瘤谱第3位,死亡瘤谱第2位[1]。在我国,2015年CRC新发病例估计有38.76万例,死亡病例18.71万例;位列发病瘤谱第4位,死亡瘤谱第5位[2,3]。吸烟、缺乏锻炼、不健康的饮食习惯等环境因素均会增加CRC患病风险[3];此外,遗传因素也影响着CRC的发生,大型双生子研究表明CRC的遗传力约占35%[4]。可见,CRC受遗传与环境因素共同作用。随着人类基因组计划等大型项目的开展以及测序技术的进步,利用全基因组关联研究(genome-wide association studies, GWAS)发现了大量结直肠癌易感位点,为了解和防治结直肠癌提供信息。
A:启动子区SNP的潜在功能机制。通过影响与转录因子的结合,调控靶基因的表达,影响结直肠癌发生;B:内含子区SNP的潜在功能机制。常在转录因子的参与下,通过远距离启动子增强子相互作用,影响靶基因表达;C:3ʹUTR区SNP的潜在功能机制。往往通过改变与miRNA的结合,影响靶基因转录后水平;D:外显子区SNP的潜在功能机制。可能通过改变氨基酸序列,影响蛋白与蛋白之间的相互作用。 Fig. 2Summary of the potential functional mechanisms of causal SNPs
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