Journal Article

DKFZ-2023-00107

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases.

Ugai, T. ; Akimoto, N. ; Haruki, K. ; Harrison, T. A. ; Cao, Y. ; Qu, C. ; Chan, A. T. ; Campbell, P. T. ; Berndt, S. I. ; Buchanan, D. D. ; Cross, A. J. ; Diergaarde, B. ; Gallinger, S. J. ; Gunter, M. J. ; Harlid, S. ; Hidaka, A. ; Hoffmeister, M.DKFZ* ; Brenner, H.DKFZ* ; Chang-Claude, J.DKFZ* ; Hsu, L. ; Jenkins, M. A. ; Lin, Y. ; Milne, R. L. ; Moreno, V. ; Newcomb, P. A. ; Nishihara, R. ; Obon-Santacana, M. ; Pai, R. K. ; Sakoda, L. C. ; Schoen, R. E. ; Slattery, M. L. ; Sun, W. ; Amitay, E.DKFZ* ; Alwers, E.DKFZ* ; Thibodeau, S. N. ; Toland, A. E. ; Van Guelpen, B. ; Zaidi, S. H. ; Potter, J. D. ; Meyerhardt, J. A. ; Giannakis, M. ; Song, M. ; Nowak, J. A. ; Peters, U. ; Phipps, A. I. ; Ogino, S.

2023
Springer Tokyo

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Please use a persistent id in citations: doi:10.1007/s00535-023-01955-2

Abstract: 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.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.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.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.

Keyword(s): Biogeography ; Epigenetics ; Mismatch repair ; Molecular pathological epidemiology ; Young-onset cancer

Note: 2023 Mar;58(3):229-245

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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