Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer.
OBJECTIVE
We hypothesized that adverse prognostic associations of specific tumor molecular factors vary by patient age at colorectal cancer diagnosis.


METHODS
We examined the prognostic associations and interactions by age at colorectal cancer diagnosis (<60 vs. 60-74 vs. ≥75 years old) of key molecular factors-CpG island methylator phenotype (CIMP), microsatellite instability (MSI), KRAS, BRAF, and PIK3CA mutations, and nuclear CTNNB1 expression status-on colorectal cancer-specific survival (CSS) and overall survival (OS), using 1,280 incident colorectal cancer cases (median age, 69 years; range, 38-91 years) within the Nurses' Health Study and Health Professionals Follow-up Study cohorts.


RESULTS
MSI-high was associated with better survival, whereas BRAF mutation was associated with worse survival, but these associations did not appreciably differ by age group. Status of CIMP, KRAS mutation, or PIK3CA mutation was not associated with prognosis regardless of age. Nuclear CTNNB1 expression was associated with a trend toward worse prognosis among older adults [age ≥ 75 years; multivariate HR, 1.67; 95% confidence interval (CI), 0.89-3.13 (for CSS); multivariate HR, 1.44; 95% CI, 0.93-2.24 (for OS)] but not among younger patients, and there was a statistically significant interaction by age (Pinteraction = 0.03 for CSS; Pinteraction = 0.007 for OS).


CONCLUSIONS
Tumor nuclear CTNNB1 expression may be associated with higher mortality among older patients with colorectal cancer but not among younger patients. Our findings need to be confirmed in independent datasets. Detailed exploration of tumor molecular signatures in older patients with colorectal cancer in large populations is warranted.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. nj_mccleary@dfci.harvard.edu.
Nadine J
NJ
McCleary
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Kaori
K
Sato
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Reiko
R
Nishihara
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Kentaro
K
Inamura
Department of Pathology, University of Tokyo Hospital, Tokyo, Japan.
Teppei
T
Morikawa
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Xuehong
X
Zhang
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Kana
K
Wu
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Mai
M
Yamauchi
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Sun A
SA
Kim
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Yasutaka
Y
Sukawa
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Kosuke
K
Mima
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Zhi Rong
ZR
Qian
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Charles S
CS
Fuchs
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Shuji
S
Ogino
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Jeffrey A
JA
Meyerhardt
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D015897:Comorbidity; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis
D014408:Biomarkers, Tumor