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Background <p>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.</p> Methods <p>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&#xa0;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.</p> Results <p>All DNAm-BMI scores showed consistent correlations with self-reported BMI at CRC diagnosis and up to14 years prior (Spearman <i>r</i> = 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月28日

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  • Tanwei Yuan,
  • Marko Mandic,
  • Xianzhe Li,
  • Melanie Bewerunge-Hudler,
  • Hermann Brenner,
  • Michael Hoffmeister

摘要

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.