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

Buchanan, Daniel D., Win, Aung K., Walsh, Michael D., Walters, Rhiannon J., Clendenning, Mark, Nagler, Belinda, Pearson, Sally-Ann, Macrae, Finlay A., Parry, Susan, Arnold, Julie, Winship, Ingrid, Giles, Graham G., Lindor, Noralane M., Potter, John D., Hopper, John L., Rosty, Christophe, Young, Joanne P. and Jenkins, Mark A. (2013) Family history of colorectal cancer in BRAF p.V600E-mutated colorectal cancer cases. Cancer Epidemiology Biomarkers and Prevention, 22 5: 917-926. doi:10.1158/1055-9965.EPI-12-1211


Author Buchanan, Daniel D.
Win, Aung K.
Walsh, Michael D.
Walters, Rhiannon J.
Clendenning, Mark
Nagler, Belinda
Pearson, Sally-Ann
Macrae, Finlay A.
Parry, Susan
Arnold, Julie
Winship, Ingrid
Giles, Graham G.
Lindor, Noralane M.
Potter, John D.
Hopper, John L.
Rosty, Christophe
Young, Joanne P.
Jenkins, Mark A.
Title Family history of colorectal cancer in BRAF p.V600E-mutated colorectal cancer cases
Formatted title
Family history of colorectal cancer in BRAF p.V600E-mutated colorectal cancer cases
Journal name Cancer Epidemiology Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
1538-7755
Publication date 2013-05
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-12-1211
Open Access Status DOI
Volume 22
Issue 5
Start page 917
End page 926
Total pages 10
Place of publication United States
Publisher American Association for Cancer Research
Collection year 2014
Language eng
Formatted 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.

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.
Keyword Island methylator phenotype
Colon-cancer
Microsatellite instability
Lynch-syndrome
Line-1 methylation
Serrated polyps
DNA methylation
Poor survival
Case series
Mutation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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