遗传 ›› 2021, Vol. 43 ›› Issue (3): 203-214.doi: 10.16288/j.yczz.20-320

• 综述 • 上一篇    下一篇

后GWAS时代结直肠癌致病SNP功能机制的研究进展

李以格1,2,3(), 张丹丹1,2,3()   

  1. 1 浙江大学医学院病理学与病理生理学系,杭州 310058
    2 浙江大学医学院附属第二医院肿瘤内科,杭州 310058
    3 浙江省疾病蛋白质组学重点实验室,杭州 310058;
  • 收稿日期:2020-12-01 发布日期:2021-01-14
  • 基金资助:
    国家自然科学基金项目(81773027);国家自然科学基金项目(81101640);浙江省自然科学基金项目(LY21H160027);中央高校基本科研业务费专项资金资助

Progress on functional mechanisms of colorectal cancer causal SNPs in post-GWAS

Yige Li1,2,3(), Dandan Zhang1,2,3()   

  1. 1 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;
  • Received:2020-12-01 Published:2021-01-14
  • Supported by:
    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

摘要:

结直肠癌(colorectal cancer, CRC)是受遗传与环境因素共同影响的复杂疾病,其中遗传因素发挥重要作用。至今,全基因组关联研究(genome-wide association studies, GWAS)已经发现了大量与结直肠癌风险相关的遗传变异。随之而来的后GWAS时代,越来越多的研究侧重于利用多组学数据和功能实验对潜在的致病位点进行解析。分析表明绝大多数风险单核苷酸多态性(single nucleotide polymorphism, SNP)位于非编码区,可能通过影响转录因子结合、表观遗传修饰、染色质可及性、基因组高级结构等,调控靶基因表达。本文对后GWAS时代结直肠癌致病位点的机制研究进行综述,阐述了后GWAS对于理解结直肠癌分子机制的重要意义,并探讨了结直肠癌GWAS的应用和前景,为实现GWAS成果转化提供参考。

关键词: 结直肠癌, 后全基因组关联研究, 单核苷酸多态性, 致病变异

Abstract:

Colorectal cancer (CRC) is caused by genetic and environmental factors, and the genetic component plays a significant role in CRC development. Currently, genome-wide association studies (GWAS) have identified a large number of genetic loci associated with CRC risk. In the post-GWAS era, more and more efforts focus on deciphering the biological mechanisms behind these potential causal variants by using multi-omics data and functional experiments. Many analyses have revealed that most risk single nucleotide polymorphisms (SNPs) are located in non-coding regions and these variants may regulate the expression of target genes by altering the transcription factor-binding motif, epigenetic modification, chromatin accessibility or 3D genome conformation. Results obtained from post-GWAS era have highlighted the possibility of moving from association to function. In this review, we summarize the current status of CRC post-GWAS studies and discusses the clinical application as well as future directions of CRC GWAS, in order to better gain insight into the molecular basis of CRC and provide evidence for prevention.

Key words: colorectal cancer, post-GWAS, SNP, casual variant