title: An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer.
abstract: OBJECTIVE
  Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk.
  
  
  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.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Bríd M
authors.initials: BM
authors.lastname: Ryan
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.affiliation: Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton Surrey SM2 5NG, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Khan
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Dillon
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Alessio
authors.initials: A
authors.lastname: Paone
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Abbie
authors.initials: A
authors.lastname: Lundgreen
authors.affiliation: Department of Research, Kaiser Permanente Medical Research Program, 2000 Broadway, Oakland, CA 94612, USA.
authors.forename: Bette
authors.initials: B
authors.lastname: Caan
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Centre for Public Health Research, Massey University, Wellington, New Zealand; Department of Epidemiology, University of Washington, Seattle, WA 98109, USA.
authors.forename: John
authors.initials: J
authors.lastname: Potter
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Brown
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Croce
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: Curtis_Harris@nih.gov.
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics*; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D003424:Crohn Disease / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D050796:STAT3 Transcription Factor
keywords: Colon cancer; Inflammatory bowel disease; STAT3