A team led by researchers at The University of Texas MD Anderson Cancer Center reported its findings at the American Association for Cancer Research (AACR) Annual Meeting 2013 in Washington.
"Our study indicates male smokers with low levels of bilirubin are a high-risk group that can be targeted with smoking cessation help, low-dose spiral CT screening of their lungs and other preventive measures," said senior author Xifeng Wu.
Lung cancer usually is diagnosed at a late stage, when tumours are inoperable and treatments largely ineffective.
The National Lung Screening Trial found that low-dose spiral computed tomography screening reduces mortality among heavy smokers by 20 per cent.
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However, 95 per cent of growths found by spiral CT are false positives, a barrier to large-scale screening.
"Validated bio-markers are urgently needed to improve risk prediction for lung cancer and to reduce false positives, shifting the balance toward more effective and efficient CT screening for cancer detection," Wu said in a statement.
They analysed 60 samples divided into three groups known as "trios" - normal controls, early stage and late stage non-small cell lung cancer patients. The top three metabolites were validated in two more groups of 50 and 123 trios.
When bilirubin emerged as the most significant metabolite, another validation study was done in a prospective cohort of 435,985 people with 208,233 men in Taiwan.
Men were divided into four groups according to their serum bilirubin levels. Lower bilirubin level was associated with significantly higher rates of both lung cancer incidence and mortality.