The Brazilian Genome Map Oncology Subproject: a nationwide multicentre hospital-based whole-genome sequencing study of breast, prostate, and colorectal cancer.

Abstract

The Brazilian Genome Map Oncology Subproject (BGMO) integrates paired germline and tumour WGS with lifestyle assessment across Brazil. We aimed to describe clinical, lifestyle, and genomic characteristics of probands with breast, prostate, and colorectal cancers and cascade-testing results in relatives. We conducted a cross-sectional analysis of 275 unrelated adults with breast (BC), prostate (PC), or colorectal cancer (CRC) across nine centres. Paired blood-tumour WGS was performed, and pathogenic/likely pathogenic (P/LP) germline variants were assessed using a 106-gene virtual panel. Somatic oncogenic/likely oncogenic variants were classified by tier. Lifestyle exposures before diagnosis were recorded with a questionnaire. First- and second-degree relatives of probands with P/LP variants in cancer-susceptibility genes were invited for targeted testing. The cohort included 140 BC (50.9%), 65 PC (23.6%), and 70 CRC (25.5%). Overall, 174 (63.3%) participants were women; mean age at diagnosis was 58.4 years (range 29-87). Most self-identified as brown (58.9%), followed by white (29.8%) and black (9.5%). Thirty-three probands (12.0%) carried P/LP germline variants, including 26 (9.5%) in cancer-susceptibility genes. Fifty relatives from 26 families underwent targeted testing; 19 (38.0%) carried the familial variant. Somatic WGS was successful in 269 probands; 88 tumours harboured 91 Tier 1 variants. This multicentre hospital-based WGS study provides an early snapshot of germline, somatic, lifestyle, and familial genetic findings in three high-burden cancers in Brazil and supports expansion to larger, longitudinal BGMO phases. Brazilian Ministry of Health (PROADI-SUS programme).