Projects per year
location of sampling. The rs3087967 genotype (chr11q23.1 risk variant) exhibited significant site-specific effects - risk of distal CRC (OR=1.20, P=8.20x10-20) with negligible effects on proximal CRC risk (OR=1.05, P=0.10). Expression of 1261 genes differed between proximal and distal colonic mucosa (top hit PRAC gene, fold-difference=10, P=3.48x10-57). In eQTL studies, rs3087967 genotype was associated with expression of 8 cis- and 21 trans-genes. Four of these (AKAP14, ADH5P4, ASGR2, RP11-342M1.7) showed differential effects by site, with strongest transeQTL signals in proximal colonic mucosa (e.g. AKAP14, beta=0.61, P=5.02x10-5) and opposite signals in distal mucosa (AKAP14, beta=-0.17, P=0.04). In summary, genetic variation at the chr11q23.1 risk locus imparts greater risk of distal rather than proximal CRC and exhibits site-specific differences in eQTL effects in normal mucosa.
Topographical differences in genomic control over gene expression relevant to CRC risk may underlie site-specific variation in CRC. Results may inform individualised CRC screening programmes.
- single-nucleotide polymorphism
- colorectal cancer
1/05/17 → 30/04/23