Journal Article DKFZ-2026-01297

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Epigenetic indicators of body mass predict survival outcomes in colorectal cancer patients: patient cohort analysis.

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2026
BioMed Central London

Genome medicine 18(1), 73 () [10.1186/s13073-026-01678-y]
 GO

Abstract: The prognostic relevance of body mass index (BMI) in colorectal cancer (CRC) remains controversial, partly due to disease-related weight loss. DNA methylation (DNAm)-based BMI scores may be a more stable prognostic indicator than a single BMI measurement. This study evaluated the associations between blood-derived DNAm-BMI scores and mortality in CRC patients, compared with self-reported BMI.We analyzed data from 2,126 newly diagnosed CRC patients (41.2% women, median age 69) in the German DACHS study. Self-reported BMI at diagnosis and up to 14 years earlier and pre-diagnostic weight loss was recorded. Five externally developed and validated DNAm-BMI scores were calculated from blood DNAm. Outcomes included all-cause, CRC-specific, and non-CRC-specific mortality. Associations were estimated using Cox proportional hazards models adjusted for demographic, lifestyle, clinical, and treatment factors.All DNAm-BMI scores showed consistent correlations with self-reported BMI at CRC diagnosis and up to14 years prior (Spearman r = 0.15-0.41). Underweight at diagnosis was linked to increased all-cause mortality (adjusted hazard ratio [aHR]: 1.42, 95% confidence interval [CI]: 1.07-1.88), whereas obesity was associated with decreased risk (0.83, 95%CI: 0.70-0.99). In contrast, four of the five DNAm-BMI scores (mBMI-135, mBMI-379, mBMI-435, mBMI-1109) showed consistent, positive linear associations with mortality risk. The 135-CpG score was most predictive (1.57, 95%CI: 1.23-1.99). Most of these associations were confined to the subgroup with blood samples collected before chemo-/radiotherapy.Blood-based DNAm-BMI scores, reflecting the biological effects of adiposity exposure, were positively associated with CRC mortality, and might be useful to improve risk stratification beyond self-reported BMI.

Keyword(s): Humans (MeSH) ; Colorectal Neoplasms: mortality (MeSH) ; Colorectal Neoplasms: genetics (MeSH) ; Colorectal Neoplasms: diagnosis (MeSH) ; Female (MeSH) ; Body Mass Index (MeSH) ; Male (MeSH) ; DNA Methylation (MeSH) ; Aged (MeSH) ; Middle Aged (MeSH) ; Epigenesis, Genetic (MeSH) ; Prognosis (MeSH) ; Cohort Studies (MeSH) ; Biomarkers ; Colorectal cancer ; Epigenetics ; Obesity ; Survival

Classification:

Note: #EA:C070#LA:C070#

Contributing Institute(s):
  1. Klinische Epidemiologie der Krebsfrüherkennung (C070)
  2. Microarrays (W110)
  3. Koordinierungsstelle der Cancer Prevention GS (M320)
Research Program(s):
  1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2026
Database coverage:
Medline ; DOAJ ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2026-06-01, last modified 2026-06-01


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