Cd24 Polymorphisms And Susceptibility To Inflammatory Bowel Disease And Colorectal Cancer Risk

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the gastrointestinal tract probably resulting from an aberrant immune response to luminal microbial antigens in a genetically predisposed host. Despite significant progress in the understanding and treatment of IBD, patients have an increased risk of colorectal cancer. We have previously shown that CD24 plays an important role in the multistep process of colorectal carcinogenesis and that it may be a target for chemoprevention and antitumor therapy (Sagiv, Gastroenterol, 2006; Sagiv, Can Res, 2008; Shapira, Gastroenterol 2011). However, the role of CD24 in mediating colitis has not been elucidated. Recently, single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with disease risk and progression in autoimmune diseases and may impact breast cancer prognosis. Aim: Evaluate whether CD24 SNPs are associated with a risk for IBD. Methods: The CD24 polymorphisms: C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818) were assessed in a case-control study of an Israeli cohort comprising 138 IBD patients and 105 age- and gender-matched healthy controls. Restriction fragment length polymorphism (RFLP) analysis was performed using BstX1, Bsr1, Mfe1, and BstU1 restriction enzymes, respectively. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models. Results: C170T carriers had more IBD (OR=3.022, 95% CI: 1.748-5.223, p=0.001): UC (OR=3.002, 95% CI: 1.661-5.427, p=0.001) and CD (OR=3.077, 95% CI: 1.334-7.095 p=0.008). Carrying the A1626G and A1056G SNPs was a risk factor for IBD: OR=2.460, 95% CI: 1.420-4.259, p=0.001 and OR=1.856, 95%: 1.011-3.405, p=0.01, respectively, specifically UC: OR=2.218, 95% CI: 1.207-4.075, p=0.01 and OR=1.944, 95% CI: 0.995-3.798, p=0.01, respectively, but not for CD (p=0.086, p=0.299). A1626G and TG1527del were associated with a younger age of IBD onset (p=0.022, p=0.027, respectively). Conclusions: 1. The CD24 C170T polymorphism is associated with IBD risk. 2. CD24 A1626G and A1056G SNPs might be specifically associated with UC risk. 3. CD24 SNPs associated with an earlier onset of IBD (A1626G and TG1527del) may have a protective role. 4. CD24 may be a new IBD genetic susceptibility factor, with clinical implications in the prediction of IBD phenotype, the course of the disease, and colitis-associated cancer. Citation Format: Victoria Lisiansky, Sarah R. Kraus, Inna Naumov, Dina Kazanov, Ilana Nabiochtchikov, Ohad Toledano, Moshe Leshno, Doran Avivi, Menachem Moshkowitz, Iris Dotan, Nadir Arber. CD24 polymorphisms and susceptibility to inflammatory bowel disease and colorectal cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3645. doi:10.1158/1538-7445.AM2014-3645