Dados do Resumo

Título

Brazil Genome Map - Precision Medicine in Oncology within the SUS: Correlation Between Genomic, Epidemiological, Clinical, and Familial Profiles in Cancer.

Introdução

Cancer is responsible for 17% of deaths in Brazil, predominantly affecting Brazilians with greater social and economic vulnerability. The ethnic diversity in the country is remarkable, resulting from centuries of intermixing among Indigenous, European, African, and Asian peoples, which influences health patterns, including the incidence and distribution of cancer across states. As a project of the Institutional Development Support Program of the Unified Health System (PROADI-SUS), the study aims to support the implementation of population management strategies in cancer.

Objetivo

1. To characterize the clinical, epidemiological, and familial profiles, and to identify pathogenic (P) or likely pathogenic (LP) variants in patients with breast, prostate, and colorectal cancer, and their families.
2. To determine the spectrum and frequency of germline and somatic variants.
3. To establish and maintain a prospective database (REDCap).
4. To provide genetic counseling to patients and their families.

Métodos

Partner centers: 9 oncology-specialized centers across the 5 Brazilian regions were included.
Inclusion criteria: Pathological diagnosis of breast, prostate, or colorectal cancer in patients over 18 years of age, with no prior treatment.
Study population: 273 index cases and 2 first or second-degree relatives.
Database: Structured in REDCap for prospective collection and storage of demographic, epidemiological, clinical, familial, pathological, and molecular data.
Sample collection: Blood and tumor tissue samples (index cases) were collected for WGS analysis, and blood samples (relatives) for Sanger sequencing analysis in positive index cases.
WGS analysis: Target coverage of ≥30× for germline WGS and ≥60× for somatic WGS. Variant classification according to international guidelines: ACMG/AMP.

Resultados

A total of 304 patients were recruited from 9 specialized cancer treatment centers, representing the 5 major Brazilian regions. The final cohort included 275 patients and 515 relatives. There were 140 cases of breast cancer (50.9%), 65 of prostate cancer (23.6%), and 70 of colorectal cancer (25.5%). Among the 275 probands, a panel of 103 genes was analyzed (54 genes related to increased cancer risk and 49 related to secondary findings). Pathogenic/Likely Pathogenic variants were identified in 32 probands (11.6%), with 25 (9.1%) having variants in cancer risk-related genes and 7 (2.5%) in genes associated with secondary findings. A total of 48 relatives of the 25 probands with P/LP variants were evaluated; 19 relatives (39.6%) presented the variant previously identified in the proband. In 275 probands, 269 somatic WGS analyses were performed (6 samples were insufficient), with 90 variants identified: 53 (59.9%) in breast tumors, one (1.1%) in a prostate tumor, and 36 (40.0%) in colorectal tumors. The study was concluded on December 31, 2023.

Conclusões

WGS analysis reinforces the importance of molecular classification to guide personalized treatments. The study highlights the importance of understanding demographic characteristics, lifestyles, and medical histories across different regions to effectively target resources and strategies for cancer prevention and treatment, including variants of uncertain significance.

Financiador do resumo

Ministério da Saúde - PROADI-SUS - A Beneficência Portuguesa de São Paulo

Palavras Chave

Câncer; Sequencing; Counseling