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Epidemiology

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study

British Journal of Cancer volume 131, pages 1635–1643 (2024)Cite this article

Subjects

Abstract

Background

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent.

Methods

In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40–78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression.

Results

During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar.

Conclusions

Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

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Fig. 1
Fig. 2: Associations of bilirubin levels with the risk of colorectal cancer in Korean men and women.
Fig. 3: Associations of bilirubin levels with the risk of colorectal cancer in Korean men and women allowing for non-linearity.

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Data availability

The datasets analysed during the current study are available after the approval of the review committee of the Korea National Institute of Health. The authors are not authorized to share the data other than the approved research group.

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Acknowledgements

The authors appreciate all participants in the KoGES-HEXA Cohort Study.

Funding

This work was supported by the Austrian Science Fund (FWF, grant nr. P 32303) and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C1004608).

Author information

Author notes

  1. These authors contributed equally: Hwayoung Noh, Jeeyoo Lee.

Authors and Affiliations

  1. Department of Cancer Prevention and Environment, INSERM U1296, Leon Berard Cancer Centre, Lyon, France

    Hwayoung Noh & Beatrice Fervers

  2. Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

    Hwayoung Noh, Nazlisadat Seyed Khoei, Laia Peruchet-Noray & Heinz Freisling

  3. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

    Jeeyoo Lee, Daehee Kang & Aesun Shin

  4. Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria

    Nazlisadat Seyed Khoei & Karl-Heinz Wagner

  5. Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain

    Laia Peruchet-Noray

  6. Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Korea

    Daehee Kang & Aesun Shin

  7. Cancer Research Institute, Seoul National University, Seoul, Korea

    Aesun Shin

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Contributions

All authors have contributed to the publication according to the ICMJE guidelines for authorship. The specific contributions of each author are as follows. Study conceptualization and funding acquisition: K-HW, AS, and HF; Study concept and design: AS and HF; Data acquisition: JL, DK, and AS; data analysis: JL; supervision and interpretation of data analysis: HN, AS, and HF; Drafting of the manuscript: HN and HF; Reviewing of the manuscript: JL, NSK, LP-N, BF, AS, and HF; All authors approved the final version for submission.

Corresponding authors

Correspondence to Aesun Shin or Heinz Freisling.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This research was conducted according to the principles expressed in the Declaration of Helsinki. All study participants provided informed consent. Ethical approval was obtained from the IRBs of Seoul National University and collaborating centres of the KoGES groups, and an additional ethical approval specifically for this project was obtained from the IRB of Seoul National University College of Medicine/Hospital (Reference no.: E1810-006-974).

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The manuscript does not contain any individual person’s data. All reasonable measures have been taken to ensure the anonymity of study participants.

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Noh, H., Lee, J., Seyed Khoei, N. et al. Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study. Br J Cancer 131, 1635–1643 (2024). https://doi.org/10.1038/s41416-024-02847-9

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