Center for Tobacco Products, Food and Drug Administration, Silver Spring, MD 20993, USA.
Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Environ Res Public Health. 2021 Jul 9;18(14):7349. doi: 10.3390/ijerph18147349.
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.
烟草暴露的生物标志物已知与疾病风险相关，但以前的研究数量有限，仅限于某些地区。我们在伊朗戈勒斯坦队列研究中进行了一项嵌套病例对照研究，研究了目前男性专用卷烟吸烟者的基线水平和随后的肺癌发病率。我们计算了 28 名匹配病例和 52 名对照者的生物标志物浓度的几何平均值，以研究对照者之间生物标志物水平的相关性，以及根据生物标志物浓度计算肺癌发病率的调整比值比 (OR)，并考虑了人口统计学特征、吸烟量和吸烟时间以及鸦片使用情况。肺癌病例的大多数生物标志物（包括总尼古丁当量（TNE-2）、4-（甲基亚硝氨基）-1-（3-吡啶基）-1-丁醇（NNAL）和 3-羟基芴）的平均水平均较高。许多生物标志物彼此高度相关，包括 TNE-2 与 NNAL 和 N-乙酰-S-（2-氰乙基）-L-半胱氨酸（2CYEMA），以及 N-乙酰-S-（4-羟基-2-丁烯-1-基）-L-半胱氨酸（t4HBEMA）与 N-乙酰-S-（3-羟基丙基-1-甲基）-L-半胱氨酸（3HMPMA）和 N-乙酰-S-（4-羟基-2-甲基-2-丁烯-1-基）-L-半胱氨酸（4HMBEMA）。几项生物标志物的浓度与肺癌风险增加相关，包括 TNE-2（OR=2.22，95%CI=1.03，4.78）和 NNN（OR=2.44，95%CI=1.13，5.27），并且在进一步调整人口统计学和吸烟特征后，2CYEMA（OR=2.17，95%CI=1.03，4.55）、N-乙酰-S-（2-氨甲酰基乙基）-L-半胱氨酸（2CAEMA）（OR=2.14，95%CI=1.01，4.55）和 N-乙酰-S-（2-羟基丙基）-L-半胱氨酸（2HPMA）（OR=2.85，95%CI=1.04，7.81）的估计值也有统计学意义。调整鸦片使用后，估计值不显著。与匹配对照者相比，随后发展为肺癌的参与者的基线生物标志物浓度更高。调整吸烟暴露后，一些生物标志物的肺癌风险更高，但调整鸦片使用后则没有。
