Colorectal cancer risk genes are functionally enriched in regulatory pathways

Abstract

Colorectal cancer (CRC) is a common complex disease caused by the combination of genetic variants and environmental factors. Genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. However, the potential genetic mechanisms for newly identified CRC susceptibility variants are still unclear. Here, we selected 85 CRC susceptibility variants with suggestive association P < 1.00E-05 from the National Human Genome Research Institute GWAS catalog. To investigate the underlying genetic pathways where these newly identified CRC susceptibility genes are significantly enriched, we conducted a functional annotation. Using two kinds of SNP to gene mapping methods including the nearest upstream and downstream gene method and the ProxyGeneLD, we got 128 unique CRC susceptibility genes. We then conducted a pathway analysis in GO database using the corresponding 128 genes. We identified 44 GO categories, 17 of which are regulatory pathways. We believe that our results may provide further insight into the underlying genetic mechanisms for these newly identified CRC susceptibility variants.

CCDC12 promotes tumor development and invasion through the Snail pathway in colon adenocarcinoma

“…The gene frequency of rs8180040 was slightly different in different populations. The Asian population had the highest allele A frequency of 0.5, especially in East Asian populations; the African population had the lowest frequency of 0.23; the European population was close to the average ( A = 0.4088) [ 12 , 15 , 16 ], and our results were similar to previous studies. Hence, we inferred that rs8180040 may affect the occurrence of colorectal cancer by regulating CCDC12 expression.…”

CCDC12 Promotes Tumor Development and Invasion Through the Snail Pathway in Colon Adenocarcinoma

“…The gene frequency of rs8180040 was slightly different in different populations. The Asian population had the highest allele A frequency of 0.5, especially in East Asian populations; the African population had the lowest frequency of 0.23; the European population was close to the average (A = 0.4088), (12,20,21) and our results were similar to previous studies. Hence, we inferred that rs8180040 may affect the occurrence of colorectal cancer by regulating CCDC12 expression.…”

Association of four genetic variants with colorectal cancer in Kazakhstan population

“…Rs1035209 is located in an intergenic region of NKX2-3, SLC25A28. Lu et al [ 19 ] demonstrated its role in regulating pathways of cells differentiation in CRC pointed that the imbalance between proliferation and differentiation in colorectal cells can cause cancer [ 20 ]. Whiffin and coauthors stated that their research has identified a novel CRC susceptibility SNP rs1035209 at 10q24.2 and it is associated with CRC risk in Europeans at genome-wide levels of significance [ 21 ].…”