Abstract 927: Interleukin-23 receptor tagSNPs and colorectal neoplasia risk
Authors: Poole Elizabeth M. , Xiao Liren , Galbraith Rachel L. , Slattery Martha L. , Duggan David , Coghill Anna E. , Koepl Lisel , Hsu Li , Makar Karen W. , Curtin Karen , Muehling Jill , Taverna Darren , Caan Bette J. , Carlson Christopher S. , Peters Ulrike , Potter John D. , Ulrich Cornelia M. 
Published: February 2011

Introduction: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory conditions that predispose to colorectal cancer. Genetic variation in the interleukin-23 receptor (IL23R), specifically rs11209026 (Arg381Gln) and rs11465804 (68723 T&gt;G), have been consistently associated with CD and UC. We investigated IL23R candidate and tagSNPs in relation to colorectal neoplasia risk. All SNPs were genotyped on an identical Illumina platform in three independent study populations capturing the range of colorectal carcinogenesis.

Methods: A linkage-disequilibrium (LD)-based tagSNP selection algorithm (r2=0.90, MAF=4%) identified 23 tagSNPs, including the candidates rs11209026 and rs11465804, representing common genetic variation in Europeans. In three US population-based case-control studies of colon cancer (n=1424 cases/1780 controls), rectal cancer (n=583 cases/775 controls), and colorectal adenomas (n=485 cases/578 controls), we investigated IL23R SNPs. Gene-level analyses were conducted using principal components and haplotype analyses. Single SNPs were analyzed using logistic regression. All analyses were adjusted for age, sex, and study center, and were restricted to Caucasians (&gt;90% of all study populations).

Results: No associations were observed for the IL23R candidate SNPs, although there was a suggestion of increased adenoma and rectal cancer risk with rs11465804. Without correction for multiple testing, three SNPs were associated with rectal cancer risk at α=0.05 (see Table). Of these, rs10889675 was also associated with a non-significant decreased risk of adenomas. There were no significant associations with colon cancer; however, the homozygous variant genotype of rs10889676 was associated with increased adenoma risk.

Conclusion: These data provide evidence that genetic variability in IL23R may contribute to rectal cancer risk and adds some further support to the role of IL23R in gastrointestinal diseases. Functional follow-up studies are needed.Table.Selected tagSNPS in IL23R and risk of rectal cancer or adenomaSNPGenotypeCasesControlsOR95% CIp (2df)p-trendRectal cancer*rs10889675CC4675831.00-    CA1091790.760.581.00   AA7130.680.271.730.110.04         rs11465770CC4786051.00-    CT981530.800.611.07   TT2110.220.051.010.030.03         rs7542081CC2523141.00-    CA2713480.970.771.22   AA581120.650.450.920.040.05         Colorectal Adenoma**rs10889676CC2352811.00-    CA1962680.870.671.14   AA50331.610.982.660.050.50*Adjusted for age, sex, and study center.**Adjusted for age and sex.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 927.