= Solution
\b[An increased colorectal-cancer risk is mechanistically plausible in the supplied model, but not demonstrated by these data.] Reduced normal TCF-long production and a shift toward TCF-short could weaken a differentiated-cell expression program and favor proliferation. This resembles one functional consequence of truncating long products, but the splice-site allele and repeat <frameshift mutations> are distinct changes, and the allele need not itself impair <DNA mismatch repair>. The pancreatic <HNF1β> reporter result cannot establish the mechanism in colon <epithelium>, where the relevant cofactors and targets differ.
Determine actual allele-specific isoforms and total <protein> in colon tissue, test proliferation and differentiation in matched edited cells or <organoids>, and compare allele frequencies in well-controlled case and population samples. \b[The table of repeat mutations supplies no direct association test for this SNP.] The designation as a diabetes-risk allele alone does not establish either the direction or size of a colorectal-cancer association.
Back to article page
