Family History of Colorectal Cancer in BRAF p.V600E mutated Colorectal Cancer Cases
Menée en population australienne auprès de 690 participants, cette étude analyse l'association entre une histoire familiale de cancer colorectal et le risque de cancer colorectal chez des membres de la famille porteurs de la mutation p.V600E du gène BRAF
Background: Previous reports suggest that relatives of CRC-affected probands carrying the BRAF p.V600E mutation are at an increased risk of colorectal (CRC) and extracolonic cancers (ECCs). In this study, we estimated the association between a family history (FH) of either CRC or ECC and risk of CRC with a BRAF p.V600E mutation. Methods: Population-based CRC cases (probands; aged 18-59years at diagnosis), recruited irrespective of family cancer history, were characterised for BRAF p.V600E mutation and mismatch repair (MMR) status. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Results: The 690 eligible probands demonstrated a mean age at CRC diagnosis of 46.9±7.8years, with 313 (47.9%) reporting a FH of CRC and 53 (7.7%) that were BRAF-mutated. Probands with BRAF-mutated, MMR-proficient CRCs were less likely to have a FH of CRC than probands that were BRAF-wildtype (OR=0.46, 95%CI=0.24-0.91; p=0.03). For probands with a BRAF-mutated CRC, the mean age at diagnosis was older for those with a CRC-affected first- or second-degree relative (49.3±6.4 years) compared with those without a FH (43.8±10.2 years; p=0.04). The older the age at diagnosis of CRC with the BRAF p.V600E mutation, the more likely these probands demonstrated a FH of CRC (OR=1.09 per year of age; 95%CI=1.00-1.18; p=0.04). Conclusions: Probands with early-onset, BRAF-mutated and MMR-proficient CRC were less likely to have a FH of CRC than probands that were BRAF-wildtype. Impact: These findings provide useful insights for cancer risk assessment in families and suggest that familial factors are more important in early-onset, BRAF-wildtype CRC.