TY - JOUR
T1 - Family history of colorectal cancer in BRAF p.V600emutated colorectal cancer cases
AU - Buchanan, Daniel D
AU - Win, Aung K
AU - Walsh, Michael D.
AU - Walters, Rhiannon J.
AU - Clendenning, Mark
AU - Nagler, Belinda
AU - Pearson, Sally Ann
AU - Macrae, Finlay A
AU - Parry, Susan
AU - Arnold, Julie
AU - Winship, Ingrid
AU - Giles, Graham G.
AU - Lindor, Noralane M
AU - Potter, John D.
AU - Hopper, John L.
AU - Rosty, Christophe
AU - Young, Joanne P
AU - Jenkins, Mark A.
PY - 2013/5
Y1 - 2013/5
N2 - 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 CRCswere less likely to have a family history ofCRCthan probands that wereBRAFwild-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, andMMR-proficientCRCwere 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. Cancer Epidemiol Biomarkers Prev; 22(5); 917-26.
AB - 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 CRCswere less likely to have a family history ofCRCthan probands that wereBRAFwild-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, andMMR-proficientCRCwere 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. Cancer Epidemiol Biomarkers Prev; 22(5); 917-26.
UR - http://www.scopus.com/inward/record.url?scp=84877931368&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-12-1211
DO - 10.1158/1055-9965.EPI-12-1211
M3 - Article
C2 - 23462926
AN - SCOPUS:84877931368
VL - 22
SP - 917
EP - 926
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
SN - 1055-9965
IS - 5
ER -