title: Family history of colorectal cancer in BRAF p.V600E-mutated colorectal cancer cases.
abstract: BACKGROUND
  Previous reports suggest that relatives of colorectal cancer (CRC)-affected probands carrying the BRAF p.V600E mutation are at an increased risk of CRC and extracolonic cancers (ECC). In this study, we estimated the association between a family history of either CRC or ECC and risk of CRC with a BRAF p.V600E mutation.
  
  
  METHODS
  Population-based CRC cases (probands, ages 18-59 years at diagnosis), recruited irrespective of family cancer history, were characterized for BRAF p.V600E mutation and mismatch repair (MMR) status. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression.
  
  
  RESULTS
  The 690 eligible probands showed a mean age at CRC diagnosis of 46.9 ± 7.8 years, with 313 (47.9%) reporting a family history of CRC and 53 (7.7%) that were BRAF-mutated. Probands with BRAF-mutated, MMR-proficient CRCs were less likely to have a family history of CRC than probands that were BRAF wild-type (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 greater for those with a CRC-affected first- or second-degree relative (49.3 ± 6.4 years) compared with those without a family history (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 were to show a family history 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 family history of CRC than probands that were BRAF-wild-type.
  
  
  CONCLUSIONS
  These findings provide useful insights for cancer risk assessment in families and suggest that familial or inherited factors are more important in early-onset, BRAF-wild-type CRC.
authors: Cancer and Population Studies Group, Queensland Institute of Medical Research, 300 Herston Rd, Herston QLD 4006, Australia. Daniel.Buchanan@qimr.edu.au
authors: Daniel D
authors: DD
authors: Buchanan
authors: Aung K
authors: AK
authors: Win
authors: Michael D
authors: MD
authors: Walsh
authors: Rhiannon J
authors: RJ
authors: Walters
authors: Mark
authors: M
authors: Clendenning
authors: Belinda
authors: B
authors: Nagler
authors: Sally-Ann
authors: SA
authors: Pearson
authors: Finlay A
authors: FA
authors: Macrae
authors: Susan
authors: S
authors: Parry
authors: Julie
authors: J
authors: Arnold
authors: Ingrid
authors: I
authors: Winship
authors: Graham G
authors: GG
authors: Giles
authors: Noralane M
authors: NM
authors: Lindor
authors: John D
authors: JD
authors: Potter
authors: John L
authors: JL
authors: Hopper
authors: Christophe
authors: C
authors: Rosty
authors: Joanne P
authors: JP
authors: Young
authors: Mark A
authors: MA
authors: Jenkins
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf