Functional annotation of colorectal cancer susceptibility loci identifiesMLH1rs1800734 associated with MSI patients

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 …