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Background <p>Smoking is a well-established risk factor for colorectal cancer (CRC) development. However, the reliability of DNA methylation-based smoking signatures in predicting smoking status and their prognostic value in CRC remain unclear, particularly across different biological sample types.</p> Results <p>Five previously validated methylation-based smoking signatures were analyzed in 2237 CRC patients with blood-derived DNA and 2273 patients with tumor tissue-derived DNA. Blood-derived signatures showed strong correlations with self-reported smoking status, effectively differentiating current smokers from never smokers (all <i>p</i> &lt; 0.0001), with excellent discriminative ability (median area under the receiver operating characteristic curve: 0.94). In contrast, tumor tissue-derived signatures exhibited much weaker associations with smoking status. Among non-metastatic CRC patients, blood-derived methylation signatures were significantly associated with increased risks of all-cause and non-CRC-related mortality, but not with CRC-specific mortality. Conversely, two tumor tissue-derived signatures demonstrated stronger associations with CRC-specific mortality compared to blood-derived signatures.</p> Conclusions <p>Blood-derived methylation-based smoking signatures are robust indicators for smoking exposure and are associated with increased mortality risk among non-metastatic CRC patients. When applied to tumor tissue, signatures showed stronger associations with CRC-specific mortality.</p>

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Methylation-based smoking signatures in blood and tissue samples for the prediction of self-reported smoking status and mortality in patients with colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月3日

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  • Tanwei Yuan,
  • Katrin E. Tagscherer,
  • Wilfried Roth,
  • Melanie Bewerunge-Hudler,
  • Alexander Brobeil,
  • Matthias Kloor,
  • Hendrik Bläker,
  • Hermann Brenner,
  • Michael Hoffmeister

摘要

Background

Smoking is a well-established risk factor for colorectal cancer (CRC) development. However, the reliability of DNA methylation-based smoking signatures in predicting smoking status and their prognostic value in CRC remain unclear, particularly across different biological sample types.

Results

Five previously validated methylation-based smoking signatures were analyzed in 2237 CRC patients with blood-derived DNA and 2273 patients with tumor tissue-derived DNA. Blood-derived signatures showed strong correlations with self-reported smoking status, effectively differentiating current smokers from never smokers (all p < 0.0001), with excellent discriminative ability (median area under the receiver operating characteristic curve: 0.94). In contrast, tumor tissue-derived signatures exhibited much weaker associations with smoking status. Among non-metastatic CRC patients, blood-derived methylation signatures were significantly associated with increased risks of all-cause and non-CRC-related mortality, but not with CRC-specific mortality. Conversely, two tumor tissue-derived signatures demonstrated stronger associations with CRC-specific mortality compared to blood-derived signatures.

Conclusions

Blood-derived methylation-based smoking signatures are robust indicators for smoking exposure and are associated with increased mortality risk among non-metastatic CRC patients. When applied to tumor tissue, signatures showed stronger associations with CRC-specific mortality.