Methods: We selected 15 validated SNPs associated with risk of either Crohn’s disease, ulcerative colitis,
or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a
two-stage study design.
Results: We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however,
the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the
effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower
expression of STAT3 mRNA in TP53 wild-type, but not mutant, tumors.
Conclusions: These data suggest that the STAT3 locus is associated with both IBD and cancer. Further
understanding the function of this variant in relation to TP53 could possibly explain the role of this gene
in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD,
could help to resolve the relationship between this SNP and cancer