Development of Polygenic Risk Scores in Colon Cancer Patients Through the Study of Ancestry and Diversity in Genetic Maps of the Brazilian Population - ORIGEM Project (ORIGEM)

Development of a polygenic risk score based on somatic and germline genetic information from patients with colorectal cancer

Study Overview

• Status: Enrolling by invitation
• Conditions: Colo-rectal Cancer; Hereditary Cancer; Somatic Mutation; Cancer Predisposition Syndrome; Germline Mutations; Polygenic Risk Score

Detailed Description

Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women. Approximately 70% of CRC cases originate from spontaneous point mutations in oncogenes, tumor suppressor genes, and genes related to DNA repair mechanisms (Nigin et al., 2023). The remaining 30% result from hereditary mutations, of which 5-6% involve high-penetrance genes. Genetic predisposition due to pathogenic germline variants in high-risk cancer-associated genes has been implicated in 2-8% of all CRC cases, increasing to 6-10% when considering pathogenic mutations in both high- and moderate-penetrance genes.

For individuals with certain hereditary cancer syndromes, the risk of developing colorectal cancer can reach 50-80% in the absence of endoscopic and/or surgical intervention. Therefore, characterizing high-, moderate-, and low-penetrance genes within a population is crucial for understanding hereditary tumorigenesis and guiding more cost-effective screening strategies.

Genetic studies comparing genomes from populations of different ethnic backgrounds have demonstrated that ancestry plays a significant role in genetic predisposition to CRC. Given the high level of genetic admixture in the Brazilian population, studies focused solely on populations of European ancestry fail to provide a representative model for application in highly admixed populations like Brazil.

In this context, the present study aims to utilize next-generation sequencing (NGS) in a cohort representative of the Brazilian population with CRC and controls to develop a Polygenic Risk Score (PRS). This score could impact cancer screening and prevention strategies, as well as genetic counseling for patients and their families. The hypothesis is that genetic mapping-including ancestry, germline, and tumor genetic variability-in Brazilian colorectal cancer patients will provide valuable data for developing a PRS that may eventually guide more targeted and cost-effective screening strategies for our population.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 40414-120
      • CPOC - Centro de Pesquisa Oncológica e Clínica, faz parte do Complexo Associação Obras Sociais lrmã Dulce (AOSID)
    • Salvador, BA, Brazil, 40414-120
      • Instituto D'Or de Pesquisa e Ensino
  • CE
    • Fortaleza, CE, Brazil, 60135-237
      • Instituto D'Or de Pesquisa e Ensino
  • DF
    • Brasilia, DF, Brazil, 70390-140
      • Instituto D'Or de Pesquisa e Ensino
  • PE
    • Recife, PE, Brazil, 52010-010
      • Instituto D'Or de Pesquisa e Ensino
  • PR
    • Curitiba, PR, Brazil, 80420-090
      • Instituto D'Or de Pesquisa e Ensino
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22281-100
      • Instituto D'Or de Pesquisa e Ensino
  • SP
    • São Paulo, SP, Brazil, 04.501-000
      • Instituto D'Or de Pesquisa e Ensino
    • São Paulo, SP, Brazil, 05403-010
      • Instituto do Cancer do Estado de São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Of the 500 patients included, approximately 56% will be recruited from participants self-identified as brown, black, or indigenous, with the remaining percentage distributed between white and yellow. Of these individuals, at least 50% will be women, corresponding to the sex and race distribution in the Brazilian population reported in the latest IBGE census in 2022.

Description

Inclusion Criteria:

• > 18 years;
• Histologically confirmed diagnosis of colorectal cancer;
• Have available tumor material for somatic sequencing, obtained from biopsy or routine surgery;
• Sign the informed consent form (ICF) for the study.

Exclusion Criteria:

• Pregnants

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elaboration of Poligenic Risk	A germline and somatic genetic mapping in Brazilian patients with colon adenocarcinoma, including ancestry, for the development of a polygenic risk score system applicable to the Brazilian population.	36mo

Collaborators and Investigators

• Sponsor: D'Or Institute for Research and Education

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Estimated): April 8, 2025

Study Record Updates

• Last Update Posted (Estimated): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility; Genetic Predisposition to Disease; Genetic Risk Score
• Other Study ID Numbers: 25000.130491/2023-48 - ORIGEM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No