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.
In the Taiwanese cohort, the incidence rate per 10,000 person-years in men was 7.02 for those in the lowest bilirubin quartile (.68 mg/dL or less), compared to 3.73 in the highest quartile of bilirubin level (1.12 mg/dL or more). The mortality rate per 10,000 person-years was 4.84 for the lowest level compared with 2.46 in the highest bilirubin quartile.
Next step: Establish a risk prediction model in heavy smokers
Bilirubin makes sense as a protective agent because of its anti-oxidant, anti-inflammatory and anti-proliferative effects. "It's plausible that bilirubin protects against lung cancer by scavenging free radicals and carcinogens associated with smoking," said study presenter Fanmao Zhang, a doctoral candidate in epidemiology.
Indeed, a Belgian study showed that bilirubin in the high normal range lowered cancer mortality in men. A study in the United Kingdom showed higher bilirubin levels in the normal range were associated with lower risks of chronic obstructive pulmonary disease, lung cancer and all-cause mortality. Neither of those studies stratified their analysis of bilirubin by smoking status.
"We expected that bilirubin might be protective, but our finding that bilirubin levels affect only smokers was somewhat of a surprise," Wu said. "Our discovery that low levels increase lung cancer risk is unique."
Smokers in the two middle cohorts of bilirubin levels also had hi
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center