Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case-control study examining baseline levels and subsequent
lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean
biomarker concentrations for 28 matched cases and 52 controls for the correlation of
biomarker levels among controls and for adjusted odds' ratios (
ORs) for
lung cancer incidence by
biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and
opium use.
Lung cancer cases had higher average levels of most
biomarkers including total
nicotine equivalents (TNE-2),
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many
biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA).
Lung cancer risk increased with concentration for several
biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55),
N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for
opium use. Concentrations of many
biomarkers were higher at the baseline for participants who subsequently developed
lung cancer than among the matched controls. Odds of
lung cancer were higher for several
biomarkers including with adjustment for smoking exposure for some but not with adjustment for
opium use.