Abstract CRC incidence in patients <50 years of age has increased by 17% in the last decade predominantly rectal cancer in Whites (Siegel et al, 2009). This age group is rarely screened. We determined the rectal binding Adnab-9 antibody in patients <50 years and a >50 year control at high clinical CRC risk of cancer. Methods: Adnab-9 is an adenoma-carcinoma sequence marker. We performed Adnab-9 immunohistocemistry on colonoscopic rectal biopsies. Results: Our study found that of 25 patients age <50 years, 48% had rectal binding of Adnab-9 versus 21.8% in 220 patients ≥50yrs (p<0.01) and with BMI was confirmed as an independent risk factor by multivariate analysis. Demographics are summarized (Table) and significant differences were seen for gender, ASA intake and BMI, however female gender was equally distributed 58.3 in the positive and 61.5% in the negative group. Hematochezia tended (p=0.23) to associate with positive rectal binding (50 versus 23%) and the colonoscopic finding was more likely to reveal adenomatous tissue in the positive group (58.3 versus 23.1%, p=0.11). Older patients were significantly more likely to take ASA which may have reduced the polyp number in this group and they also have an decreased BMI (p<0.02). In the entire group Adnab-9 positivity correlated with BMI as a continuous variable (U=0.03; p<0.01). Conclusions: Adnab-9 is an independent CRC risk marker in patients <50 years of age suggesting that they are more prone to development of neoplasia. The mechanism appears to be that of an adenoma-carcinoma sequence. ASA may be a factor but was not an independent mitigating marker in this study. BMI is also greater in the younger group and may be the underlying cause of the observed increase in neoplasia in the young. Adnab-9 staining of sigmoidoscopic rectal biopsies may be a convenient way of identifying a high-risk population of patients <50 years of age for CRC surveillance in this population hithertofore not afforded screening.Parameter (n)Patients <50 (25)Patients >50 (220)Age(mean+st.deviationSD)44.8 (5.4)62.4 (9.3)% Non-Hispanic Whites4041.4% Female Gender60 (OR 11.0, CI 4.4-27.2; p<0.0001)10.9Any NSAID/Statin/ASA(%)30.4/44/41.18/4.6 (less ASA-p<0.02)37.6/46.6/30.5Symptom %/BMI(SD)60/31.6(6.1) (BMI p<0.02)*42.9/28.7(5.4) 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 2905.