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Novel Serum Biomarker Bilirubin Predicted Lung Cancer Risk in Smoker

April 7, 2013
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  • Serum metabolites are emerging biomarkers for lung cancer detection.
  • Bilirubin identified by metabolomic profiling had biomarker potential.
  • Men who were smokers and had low bilirubin levels had increased risk for cancer incidence and mortality.

WASHINGTON, D.C. — Smokers with low bilirubin levels were at increased risk for lung cancer incidence and mortality compared with those who had the highest bilirubin levels, making serum bilirubin a potential biomarker for lung cancer risk prediction, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Although it was expected that bilirubin may be protective against lung cancer incidence and mortality, we were somewhat surprised that the effect of bilirubin was only evident in smokers, which will have profound public health implications, given that 90 percent of lung cancers occur in smokers,” said Xifeng Wu, M.D., Ph.D., professor and chair of the Department of Epidemiology at The University of Texas MD Anderson Cancer Center in Houston.

Most patients with lung cancer are diagnosed at inoperable advanced stages and the prognosis is particularly dismal, with the five-year survival rate for stage 3b and stage 4 diseases being 5 percent and 1 percent, respectively, according to Wu. Biomarkers are urgently needed for improving risk prediction for lung cancer beyond smoking variables, and serum metabolites are emerging as promising markers.

Wu and colleagues used a unique multiphase study design for the metabolomics profiling of serum samples. In the initial discovery phase, the researchers recruited 20 healthy individuals, 20 patients with early-stage non-small cell lung cancer and 20 patients with late-stage non-small cell lung cancer, matched for age and gender. They performed global, unbiased metabolite profiling using the serum from patients’ blood samples. They then validated the top three differentially expressed metabolites in the next phase involving two additional populations with a total of 519 healthy individuals and patients with non-small cell lung cancer.

The metabolite bilirubin emerged as the most promising marker, and the researchers further validated this finding in the third phase, which included a large Taiwanese prospective cohort of 435,985 individuals.

Among the Taiwanese cohort, the researchers found a 7.02 incidence rate of lung cancer per 10,000 person-years for men with bilirubin levels of 0.68 mg/dL or less, compared with an incidence rate of 3.73 among men whose bilirubin levels were 1.12 mg/dL or more. This translates into a 51 percent increase in the risk for developing lung cancer for patients with low bilirubin. Researchers also found a lung cancer-specific mortality rate of 4.84 for men with the lowest levels of bilirubin compared with a mortality rate of 2.46 for men with the highest bilirubin levels — a 59 percent increase in lung cancer-specific mortality among those with the lowest bilirubin levels.

Looking only at smokers, Wu and her colleagues found that those with the lowest levels of bilirubin had a 69 percent increase in the risk for lung cancer development and a 76 percent increase in mortality compared with smokers with the highest levels of bilirubin. In contrast, there was no significant effect of bilirubin in “never-smokers.”

The association between bilirubin levels and lung cancer was only significant in “ever-smokers” and men, according to Wu.

“The ability to use low bilirubin to identify higher-risk smokers, over and above the number of ‘pack years’ smokers report having smoked, has significant public health impact in reducing lung cancer burden,” said Wu. “Low levels of bilirubin, established as an objective risk index for lung cancer incidence and mortality, may be viewed by smokers as an urgent health warning to drive them to quit.”

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About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit

Media Contact:
Jeremy Moore
(215) 446-7109
In Washington, D.C.,
April 6-10, 2013:

(202) 249-4005

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