Article Text

Download PDFPDF
Functional annotation of colorectal cancer susceptibility loci identifies MLH1 rs1800734 associated with MSI patients
  1. Gaoxiang Ma1,2,
  2. Yuqiu Ge1,2,
  3. Dongying Gu3,
  4. Mulong Du1,2,
  5. Haiyan Chu1,2,
  6. Jinfei Chen3,
  7. Zhengdong Zhang1,2,
  8. Meilin Wang1,2
  1. 1Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
  2. 2Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
  3. 3Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
  1. Correspondence to Dr Meilin Wang, Department of Environmental Genomics, School of Public Health, Nanjing Medical University, 101 Longmian Road, Nanjing, Nanjing 211166, China; mwang{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Recently, we read the article by Ma et al with great interest. They conducted a comprehensive meta-analysis that nominated 62 variants in 50 candidate genes with high level of cumulative evidence for genetic susceptibility to colorectal cancer (CRC).1 Interestingly, the authors found that 10 variants in 7 genes were graded strong and moderate association with CRC risk. However, functional annotations of these variants remain largely unknown. To investigate their functional relevance, we annotated the variants and their high related single nucleotide polymorphisms (SNPs) (linkage disequilibrium, r2>0.9) using publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus datasets.

After exclusion of the variants with minor allele frequency <0.05, a total of four SNPs (rs1801155, rs1569686, rs1800734 and rs2736100) were included in further analysis (table 1). We then evaluated the effect of risk alleles on gene epigenetic and expression alterations in CRC tumour tissues from TCGA. Three SNPs (rs1569686, rs1800734 and rs2736100) were identified as methylation quantitative trait loci (meQTL) in the 500 kb upstream and …

View Full Text


  • GM, YG and DG contributed equally to this work. ZZ and MW co-supervised this work.

  • Twitter Follow Yuqiu Ge at @gutjnl-2015-311299

  • Contributors ZZ and MW are co-responders for this paper. Study concept and design: MW and GM. Acquisition of data: GM and YG. Analysis and interpretation of data: MD, DG and HC. Drafting of the manuscript: GM and YG. Critical revision of the manuscript for important intellectual content: ZZ, MW and JC. Statistical analysis: GM and YG. Obtained funding: ZZ and MW. Approval of the final version of the manuscript: MW and ZZ.

  • Funding This study was partly supported by National Natural Science Foundation of China (81373091, 81230068 and 81201570), Distinguished Young Scholars of Nanjing (JQX13005) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; internally peer reviewed.