Cancer Causes & Control

, Volume 12, Issue 10, pp 887–894 | Cite as

Serum bilirubin and 10-year mortality risk in a Belgian population

  • Elisabeth H.M. Temme
  • Jianjun Zhang
  • Evert G. Schouten
  • Hugo Kesteloot


objective: The endogenous antioxidant serum bilirubin may scavenge free radicals and protect against free radical-related diseases. Methods: Using the 10-year follow-up mortality data from the Belgium Inter-university Research on Nutrition and Health (BIRNH) study the association between serum bilirubin and all-cause, cardiovascular, and cancer mortality in 5460 men and 4843 women was investigated. Results: In men, with the highest (≥0.6 mg/dl) compared with the lowest serum bilirubin concentration (≤0.2 mg/dl), the adjusted relative risk (RR) was 0.73 (95% confidence interval (CI) 0.57–0.94) for all-cause and 0.42 (95% CI 0.26–0.68) for cancer mortality. The risk for cancer mortality decreased with increasing concentrations of serum bilirubin (p for trend = 0.004) especially for non-lung cancer mortality (p for trend = 0.02). The associations persisted after adjusting for smoking. In women the associations between serum bilirubin and cancer mortality were in the same direction, but did not reach statistical significance (RR = 0.76, 95% CI 0.39–1.5). No significant associations were found between serum bilirubin and cardiovascular mortality in men and women. Conclusions: In this population high serum bilirubin, however, within normal ranges, was associated with low cancer mortality, especially in men. This may be due to the antioxidant activity of bilirubin. Measurement of serum bilirubin concentrations may contribute to cancer risk estimation.

bilirubin cancer cardiovascular healthy subjects mortality prospective study. 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Davies KJA (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp 61: 1-31.Google Scholar
  2. 2.
    Frei B (1994) Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med 97(Suppl. 3A): 5S-13S.Google Scholar
  3. 3.
    Halliwell B (1991) Reactive oxygen species in living systems: source, biochemistry and role in human disease. Am J Med 91(Suppl. 3C): 14S-22S.Google Scholar
  4. 4.
    Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 23: 1043-1046.Google Scholar
  5. 5.
    Neuzil J, Stocker R (1993) Bilirubin attenuates radical-mediated damage to serum albumin. FEBS Lett 331: 281-284.Google Scholar
  6. 6.
    Wu TW, Wu J, Li RK, Mickle D, Carey D (1991) Albumin-bound bilirubins protect human ventricular myocytes against oxyradical damage. Biochem Cell Biol 69: 683-688.Google Scholar
  7. 7.
    Ewing JF, Haber SN, Maines MD (1992) Normal and heatinduced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein. J Neurochem 58: 1140-1149.Google Scholar
  8. 8.
    Hopkins PN, Wu LL, Hunt SC, James BC, Vincent GM, Williams RR (1996) Higher serum bilirubin is associated with decreased risk-for early familial coronary artery disease. Arterioscler Thromb Vasc Biol 16: 250-255.Google Scholar
  9. 9.
    Schwertner HA, Jackson WG, Tolan G (1994) Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin Chem 40: 18-23.Google Scholar
  10. 10.
    Schwertner HA (1998) Association of smoking and low serum bilirubin antioxidant concentrations. Atherosclerosis 136: 383-387.Google Scholar
  11. 11.
    De Backer G (1984) Regional differences in dietary habits, coronary risk factors and mortality rates in Belgium. I. Design and methodology. Acta Cardiol 39: 285-292.Google Scholar
  12. 12.
    Gambino SR, Freda VJ (1966) The measurement of amniotic fluid bilirubin by the method of Jendrassik and Grof. Am J Clin Pathol 46: 198-203.Google Scholar
  13. 13.
    Bachorik PS, Wood PD, Albers JJ, et al. (1976) Plasma highdensity lipoprotein cholesterol concentrations determined after removal of other lipoproteins by heparin-manganese precipitation or by ultracentrifugation. Clin Chem 22: 1828-1834.Google Scholar
  14. 14.
    Kornitzer M, Dramaix M (1989) The Belgian interuniversity Research on Nutrition and Health (the BIRNH study). Acta Cardiol 94: 89-99.Google Scholar
  15. 15.
    Chan-Yeung M, Ferreira P, Frohlich J, Schulzer M, Tan F (1981) The effect of age, smoking, and alcohol on routine laboratory tests. Am J Clin Pathol 75: 320-326.Google Scholar
  16. 16.
    Frei B, Forte TM, Ames BN, Cross CE (1991) Gas phase oxidants of eigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Biochem J 277: 133-138.Google Scholar
  17. 17.
    Yamaguchi T, Shioji I, Sugimoto A, Komoda Y, Nakajima H (1994) Chemical structure of a new family of bile pigments from human urine. J Biochem 116: 298-303.Google Scholar
  18. 18.
    Yamaguchi T, Horio F, Hashizume T, et al. (1995) Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo. Biochem Biophys Res Commun 214: 11-19.Google Scholar
  19. 19.
    Stocker R, Glazer AN, Ames BN (1987) Antioxidant activity of albumin-bound bilirubin. Proc Natl Acad Sci 84: 5918-5922.Google Scholar
  20. 20.
    Vreman HJ, Wong RJ, Sanesi CA, Dennery PA, Stevenson DK (1998) Simultaneous production of carbon monoxide and thiobarbituric acid reactive substances in rat tissue preparations by an iron-ascorbate system. Can J Physiol Pharmacol 76: 1057-1065.Google Scholar
  21. 21.
    Winkel P, Statland BE, Bokelund H (1974) Factors contributing to intra-individual variation of serum constituents: 5. Short-term day-to-day and within-hour variation of serum constituents in healthy subjects. Clin Chem 20: 1520-1527.Google Scholar
  22. 22.
    Galbraith R (1999) Heme oxygenase: who needs it. Proc Soc Exp Biol Med 222: 299-305.Google Scholar
  23. 23.
    Stocker R, McDonagh AF, Glazer AN, Ames B (1990) Antioxidant activities of bile pigments: biliverdin and bilirubin. Methods Enzymol 186: 301-309.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Elisabeth H.M. Temme
    • 1
  • Jianjun Zhang
    • 1
  • Evert G. Schouten
    • 1
    • 2
  • Hugo Kesteloot
    • 1
  1. 1.Department of Public Health, Division of Nutritional EpidemiologyK.U. LeuvenLeuvenBelgium
  2. 2.Human Nutrition and EpidemiologyWageningen UniversityWageningenThe Netherlands

Personalised recommendations