Genetic variability in IL23R and risk of colorectal adenoma and colorectal cancer

Poole, Elizabeth M.; Curtin, Karen; Hsu, Li; Duggan, David J.; Makar, Karen W.; Xiao, Liren; Carlson, Christopher S.; Caan, Bette J.; Potter, John D.; Slattery, Martha L.; Ulrich, Cornelia M.

doi:10.1016/j.canep.2011.11.001

« Previous Next »Cancer Epidemiology
Volume 36, Issue 2 , Pages e104-e110, April 2012

Genetic variability in IL23R and risk of colorectal adenoma and colorectal cancer

Elizabeth M. Poole
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
Karen Curtin
- Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USA
Li Hsu
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
David J. Duggan
- Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Karen W. Makar
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Liren Xiao
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Christopher S. Carlson
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Bette J. Caan
- Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94612, USA
John D. Potter
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
Martha L. Slattery
- Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USA
Cornelia M. Ulrich
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
- National Center for Tumor Diseases and German Cancer Research Center, Heidelberg D-69120, Germany
- Corresponding author at: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Fairview Ave N, M4-B402, Seattle, WA 98109-1024, USA. Tel.: +1 49 6221 56 5528; fax: +1 49 6221 56 5231.

Received 11 May 2011; received in revised form 1 November 2011; accepted 2 November 2011. published online 18 November 2011.

Abstract

Inflammatory processes, including, specifically, the inflammatory conditions Crohn's disease (CD) and ulcerative colitis (UC) predispose to colorectal cancer. Interleukin-23 is involved in pro-inflammatory signaling; genetic variation in the interleukin-23 receptor (IL23R) has been consistently associated with CD and UC risk. In three case–control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations with 18 candidate and tagSNPs in IL23R. The three studies used an identical Illumina GoldenGate assay, allowing thorough investigation across stages and locations of colorectal neoplasia. We further explored associations with molecular cancer subtypes (MSI+, CIMP+, KRAS2mut, TP53mut). In this comprehensive study of genetic variability in IL23R across the spectrum of colorectal carcinogenesis, as well as within colon and rectal tumor molecular subtypes, we observed associations between SNPs in IL23R and risk of rectal cancer: the 88413 C>A (rs10889675) and 69450 C>A (rs7542081) polymorphisms were associated with decreased rectal cancer risk overall (p-trend=0.04 and 0.05 respectively), and specifically with rectal tumors bearing a TP53 mutation (88413 CA/AA vs. CC OR: 0.66; 95% CI: 0.46–94; 69450 CA/AA vs. CC OR: 0.60; 95% CI: 0.37–0.98). However, none of associations remained statistically significant after correction for multiple testing. These data provide some evidence that genetic variability in IL23R may contribute to rectal cancer risk and should be evaluated in additional studies.