TY - JOUR
T1 - Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations
T2 - Comparison With Later-Onset Cases
AU - Ugai, Tomotaka
AU - Haruki, Koichiro
AU - Harrison, Tabitha A.
AU - Cao, Yin
AU - Qu, Conghui
AU - Chan, Andrew T.
AU - Campbell, Peter T.
AU - Akimoto, Naohiko
AU - Berndt, Sonja
AU - Brenner, Hermann
AU - Buchanan, Daniel D.
AU - Chang-Claude, Jenny
AU - Fujiyoshi, Kenji
AU - Gallinger, Steven J.
AU - Gunter, Marc J.
AU - Hidaka, Akihisa
AU - Hoffmeister, Michael
AU - Hsu, Li
AU - Jenkins, Mark A.
AU - Milne, Roger L.
AU - Moreno, Victor
AU - Newcomb, Polly A.
AU - Nishihara, Reiko
AU - Pai, Rish K.
AU - Sakoda, Lori C.
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 - Woods, Michael O.
AU - Zaidi, Syed H.
AU - Potter, John D.
AU - Giannakis, Marios
AU - Song, Mingyang
AU - Nowak, Jonathan A.
AU - Phipps, Amanda I.
AU - Peters, Ulrike
AU - Ogino, Shuji
N1 - Publisher Copyright:
© 2023 Wolters Kluwer Health. All rights reserved.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - INTRODUCTION:Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management.METHODS:Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases.RESULTS:The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated) (all Ptrend<0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors (P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend<0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend.DISCUSSION:Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.
AB - INTRODUCTION:Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management.METHODS:Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases.RESULTS:The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated) (all Ptrend<0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors (P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend<0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend.DISCUSSION:Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.
KW - colorectal continuum
KW - colorectal neoplasm
KW - epigenetics
KW - mismatch repair
KW - molecular pathological epidemiology
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U2 - 10.14309/ajg.0000000000002171
DO - 10.14309/ajg.0000000000002171
M3 - Article
C2 - 36707929
AN - SCOPUS:85151312754
SN - 0002-9270
VL - 118
SP - 712
EP - 726
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 4
ER -