Background: Colorectal cancer (CRC) is the second most common cancer in Brazil. The Barretos Cancer Hospital (BCH) implemented a Fecal immunochemical test-based (FIT)-CRC screening program. Risk factors of the screening population and the prevalence of baseline colorectal neoplasia are important features for guiding a CRC screening strategy. This study aims to measure screening outcomes of the BCH program and associate with sociodemographic risk factors and genetic ancestry. Methods: This cross-sectional analysis included consecutive subjects between 50 and 65 years from the BCH (first round) CRC screening program. A REDCap database was built to track participants and measure clinical outcomes (adenoma, advanced adenoma (AA), and cancer). The ancestry components were analyzed using a multiplex PCR of 46 ancestry informative markers, based on insertion-deletion polymorphisms. A binary logistic regression model was used to examine the associations between sociodemographic factors and screening outcomes. Results: From Nov 2017 to Mar 2020, 2946 asymptomatic individuals were enrolled, being 83.0% females with a mean age of 57.1 ± 4.5 years, mainly from São Paulo State (79.1%). Self-reported skin color revealed 56.8% white, 36.6% brown, 5.8% black, and 0.7% yellow, and 69.9% had less than a high school diploma. The genetic ancestry revealed a mean proportion of 67.9% for European ancestry, 17.0% for African, 7.3% for East Asian, and 7.8% for Native American. A significant association was found between genetic ancestry proportions and self-reported skin colors (p<0.001). Current and former smokers comprised 41.9% of participants, 31.2% were alcohol drinkers, 73.3% reported exercise < 3x/week, and 71.9% had a BMI > 25kg/m². Of the 2946 participants, 80.7% completed and returned FIT kits. The inadequate FIT rate was 2.0%, and the positivity rate was 6.2%. The follow-up colonoscopy compliance rate was 90.5%, and the cecal intubation was successful in 99.0%. The PPV was 64.1% (86/134) for adenoma 20.1% (27/134) for AA, and 3.7% (5/134) for CRC. The five cancer patients had stage I (40.0%) or II (60.0%). The male gender (OR=2.94, 95% CI 1.06-8.17), BMI > 25kg/m² ≤ 30kg/m² (OR=5.40, 95% CI 1.42-20.52), alcohol consumption (OR=3.86, 95% CI 1.38-10.78), fried foods' consumption (OR=2.82, 95% CI 1.02-7.78) were associated to AA. Non-white skin color (OR=2.83, 95% CI 1.11-7.17), BMI > 25kg/m² ≤ 30kg/m² (OR=3.54, 95% CI 1.21-10.30), and eggs/milk consumption (OR=5.25, 95% CI 1.32-20.80) were associated to early adenoma. No association was found between genetic ancestry and screening outcomes. Conclusions: CRC detected in early stages corroborates the role of screening programs to increase the rate of early diagnosis. Further, lifestyle risk factors linked to colorectal cancer were significantly associated with the presence of a high and low-risk colorectal precursor lesion. Overall, our results in an admixed population can contribute to delineating preventive strategies and a targeted CRC screening program to improve CRC prevention and control in Brazil. Citation Format: Jun Porto, Adeylson G. Ribeiro, Lucas Henrique Viza, Laura W. Musselwhite, Thais Talarico, Maraisa Costa, Denise C. Rocha, Marco Antonio Oliveira, Jose Humberto T.G. Fregnani, Edmundo Mauad, Rui M. Reis, Dawn Provenzale, Denise P. Guimaraes. The impact of genetic ancestry and lifestyle factors on the risk of colorectal adenoma and adenocarcinoma in a Brazilian screening population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-259.