TY - JOUR
T1 - Prognostic role of detailed colorectal location and tumor molecular features
T2 - analyses of 13,101 colorectal cancer patients including 2994 early-onset cases
AU - Ugai, Tomotaka
AU - Akimoto, Naohiko
AU - Haruki, Koichiro
AU - Harrison, Tabitha A.
AU - Cao, Yin
AU - Qu, Conghui
AU - Chan, Andrew T.
AU - Campbell, Peter T.
AU - Berndt, Sonja I.
AU - Buchanan, Daniel D.
AU - Cross, Amanda J.
AU - Diergaarde, Brenda
AU - Gallinger, Steven J.
AU - Gunter, Marc J.
AU - Harlid, Sophia
AU - Hidaka, Akihisa
AU - Hoffmeister, Michael
AU - Brenner, Hermann
AU - Chang-Claude, Jenny
AU - Hsu, Li
AU - Jenkins, Mark A.
AU - Lin, Yi
AU - Milne, Roger L.
AU - Moreno, Victor
AU - Newcomb, Polly A.
AU - Nishihara, Reiko
AU - Obon-Santacana, Mireia
AU - Pai, Rish K.
AU - Sakoda, Lori C.
AU - Schoen, Robert E.
AU - Slattery, Martha L.
AU - Sun, Wei
AU - Amitay, Efrat L.
AU - Alwers, Elizabeth
AU - Thibodeau, Stephen N.
AU - Toland, Amanda E.
AU - Van Guelpen, Bethany
AU - Zaidi, Syed H.
AU - Potter, John D.
AU - Meyerhardt, Jeffrey A.
AU - Giannakis, Marios
AU - Song, Mingyang
AU - Nowak, Jonathan A.
AU - Peters, Ulrike
AU - Phipps, Amanda I.
AU - Ogino, Shuji
N1 - Publisher Copyright:
© 2023, Japanese Society of Gastroenterology.
PY - 2023/3
Y1 - 2023/3
N2 - Background: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Methods: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. Results: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70–0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15–3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Conclusions: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.
AB - Background: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Methods: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. Results: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70–0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15–3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Conclusions: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.
KW - Biogeography
KW - Epigenetics
KW - Mismatch repair
KW - Molecular pathological epidemiology
KW - Young-onset cancer
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U2 - 10.1007/s00535-023-01955-2
DO - 10.1007/s00535-023-01955-2
M3 - Article
C2 - 36648535
AN - SCOPUS:85146393347
SN - 0944-1174
VL - 58
SP - 229
EP - 245
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
IS - 3
ER -