TY - JOUR
T1 - Microsatellite instability and braf mutation testing in colorectal cancer prognostication
AU - Lochhead, Paul
AU - Kuchiba, Aya
AU - Imamura, Yu
AU - Liao, Xiaoyun
AU - Yamauchi, Mai
AU - Nishihara, Reiko
AU - Qian, Zhi Rong
AU - Morikawa, Teppei
AU - Shen, Jeanne
AU - Meyerhardt, Jeffrey A.
AU - Fuchs, Charles S.
AU - Ogino, Shuji
N1 - Funding Information:
This work was supported by the US National Institutes of Health (P01 CA87969 to S.E. Hankinson; P01 CA55075 and UM1 CA167552 to W.C. Willett; P50 CA127003 to CSF; and R01 CA151993 to SO); by the Bennett Family Fund and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance; by the Frank Knox Memorial Fellowship at Harvard University (to PL); by a fellowship from the Chief Scientist Office of the Scottish Government (to PL); and by a fellowship from the Japan Society for Promotion of Science (to TM).
PY - 2013/8/7
Y1 - 2013/8/7
N2 - BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] =1.12 to 2.28; P =. 009), 0.48 (95% CI = 0.27 to 0.87; P =. 02), and 0.25 (95% CI = 0.12 to 0.52; P <. 001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (Pinteraction >. 50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.
AB - BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] =1.12 to 2.28; P =. 009), 0.48 (95% CI = 0.27 to 0.87; P =. 02), and 0.25 (95% CI = 0.12 to 0.52; P <. 001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (Pinteraction >. 50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.
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U2 - 10.1093/jnci/djt173
DO - 10.1093/jnci/djt173
M3 - Article
C2 - 23878352
AN - SCOPUS:84881640407
SN - 0027-8874
VL - 105
SP - 1151
EP - 1156
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 15
ER -