Family history of colorectal cancer in BRAF p.V600E-mutated colorectal cancer cases

Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):917-26. doi: 10.1158/1055-9965.EPI-12-1211. Epub 2013 Mar 5.


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.

Impact: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Mismatch Repair
  • Family Health
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / genetics*


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf