Clinical trial NCT06917794: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Colo-rectal Cancer
Polygenic Risk Score
Somatic Mutation
Hereditary Cancer
Germline Mutations
Cancer Predisposition Syndrome
Lead sponsor: D'Or Institute for Research and Education
Sponsor class: OTHER
First posted: 2025-04-08
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Elaboration of Poligenic Risk
timeFrame: 36mo
Secondary outcomes:
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: CPOC - Centro de Pesquisa Oncológica e Clínica, faz parte do Complexo Associação Obras Sociais lrmã Dulce (AOSID)
state: BA
city: Salvador
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: BA
city: Fortaleza
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: CE
city: Brasilia
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: DF
city: Recife
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: PE
city: Curitiba
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: PR
city: Rio de Janeiro
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: RJ
city: São Paulo
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino
state: SP
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo
state: SP
Study officials:
References: