David Brill
A simple urine test could one day reveal which smokers are at greatest risk of developing lung cancer, according to a team of Singaporean, Chinese and American scientists.
The group recently reported the first link between elevation of certain urinary metabolites – total NNAL* – and increased lung cancer risk in humans. Cigarette smokers with the highest total NNAL levels were over twice as likely to develop lung cancer.
A commercially available test remains at least 5 years off, but the identification of these urinary biomarkers raises “an exciting possibility,” say the researchers.
“Such a test would enable doctors to screen more frequently for lung cancer in smokers with high levels of biomarkers, and provide a strong incentive for these smokers to quit smoking,” said study authors Associate Professor Yuan Jian-Min of the University of Minnesota, US, and Associate Professor Koh Woon-Puay of the National University of Singapore, in a joint statement to Medical Tribune.
“With the identification of new biomarkers, we could ultimately develop an assay that simultaneously quantifies a panel of tobacco carcinogens or their metabolites to best predict the risk of lung cancer for an individual smoker,” they said.
The work goes some way towards explaining why some smokers develop lung cancer while others do not. With over 60 established carcinogens in cigarette smoke, it may be that individual differences in the uptake and metabolism of particular chemicals play an important role in the development of cancer, the authors say.
One such carcinogen, NNK**, has been strongly linked to lung cancer but an epidemiological link had only been shown in animal studies.
Yuan, Koh and colleagues instead investigated levels of NNAL – a metabolite of NNK – in a nested case-control study using data on 63,257 men and women from the Singapore Chinese Health Study, and 18,244 men from the Shanghai Cohort Study. They identified 246 cases of incident lung cancer, and 245 matched controls. [Cancer Res 2009;69:2990-5]
The odds ratio of developing lung cancer was 2.11 for smokers who were in the highest tertile of urinary total NNAL before cancer diagnosis, compared to those in the lowest tertile (95% CI 1.25 – 3.54; P for trend = 0.005).
Combination with cotinine, a nicotine metabolite, further increased the predictive value of NNAL: the odds ratio for developing cancer was 8.47 for smokers in the highest tertile for both markers, compared to those in the lowest tertile (95% CI 3.69 – 19.46; P for trend – 0.005).
“Biomarkers for prediction of cancer risk are useful as proxy measures of outcome in interventional studies. Nevertheless, for smokers, the best intervention for the reduction of lung cancer risk is still to quit smoking,” added Yuan and Koh.
------------------------------------------------------------------------------------------------
* NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Total NNAL is the sum of NNAL and its glucuronides.
**NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
The group recently reported the first link between elevation of certain urinary metabolites – total NNAL* – and increased lung cancer risk in humans. Cigarette smokers with the highest total NNAL levels were over twice as likely to develop lung cancer.
A commercially available test remains at least 5 years off, but the identification of these urinary biomarkers raises “an exciting possibility,” say the researchers.
“Such a test would enable doctors to screen more frequently for lung cancer in smokers with high levels of biomarkers, and provide a strong incentive for these smokers to quit smoking,” said study authors Associate Professor Yuan Jian-Min of the University of Minnesota, US, and Associate Professor Koh Woon-Puay of the National University of Singapore, in a joint statement to Medical Tribune.
“With the identification of new biomarkers, we could ultimately develop an assay that simultaneously quantifies a panel of tobacco carcinogens or their metabolites to best predict the risk of lung cancer for an individual smoker,” they said.
The work goes some way towards explaining why some smokers develop lung cancer while others do not. With over 60 established carcinogens in cigarette smoke, it may be that individual differences in the uptake and metabolism of particular chemicals play an important role in the development of cancer, the authors say.
One such carcinogen, NNK**, has been strongly linked to lung cancer but an epidemiological link had only been shown in animal studies.
Yuan, Koh and colleagues instead investigated levels of NNAL – a metabolite of NNK – in a nested case-control study using data on 63,257 men and women from the Singapore Chinese Health Study, and 18,244 men from the Shanghai Cohort Study. They identified 246 cases of incident lung cancer, and 245 matched controls. [Cancer Res 2009;69:2990-5]
The odds ratio of developing lung cancer was 2.11 for smokers who were in the highest tertile of urinary total NNAL before cancer diagnosis, compared to those in the lowest tertile (95% CI 1.25 – 3.54; P for trend = 0.005).
Combination with cotinine, a nicotine metabolite, further increased the predictive value of NNAL: the odds ratio for developing cancer was 8.47 for smokers in the highest tertile for both markers, compared to those in the lowest tertile (95% CI 3.69 – 19.46; P for trend – 0.005).
“Biomarkers for prediction of cancer risk are useful as proxy measures of outcome in interventional studies. Nevertheless, for smokers, the best intervention for the reduction of lung cancer risk is still to quit smoking,” added Yuan and Koh.
------------------------------------------------------------------------------------------------
* NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Total NNAL is the sum of NNAL and its glucuronides.
**NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
No comments:
Post a Comment