Genome medicine · 2026
Epigenetic indicators of body mass predict survival outcomes in colorectal cancer patients: patient cohort analysis.
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Yuan Tanwei, Mandic Marko, Li Xianzhe, Bewerunge-Hudler Melanie, Brenner Hermann, Hoffmeister Michael
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.