Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study

Brian L Rostron; Jia Wang; Arash Etemadi; Sapna Thakur; Joanne T Chang; Deepak Bhandari; Julianne Cook Botelho; Víctor R De Jesús; Jun Feng; Mitchell H Gail; Maki Inoue-Choi; Reza Malekzadeh; Akram Pourshams; Hossein Poustchi; Gholamreza Roshandel; Meredith S Shiels; Qian Wang; Yuesong Wang; Baoyun Xia; Paolo Boffetta; Paul Brennan; Christian C Abnet; Antonia M Calafat; Lanqing Wang; Benjamin C Blount; Neal D Freedman; Cindy M Chang

doi:10.3390/ijerph18147349

Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study

Int J Environ Res Public Health. 2021 Jul 9;18(14):7349. doi: 10.3390/ijerph18147349.

Authors

Brian L Rostron¹, Jia Wang¹, Arash Etemadi^{2

3}, Sapna Thakur¹, Joanne T Chang¹, Deepak Bhandari⁴, Julianne Cook Botelho⁴, Víctor R De Jesús⁴, Jun Feng⁴, Mitchell H Gail⁵, Maki Inoue-Choi², Reza Malekzadeh³, Akram Pourshams³, Hossein Poustchi⁶, Gholamreza Roshandel⁷, Meredith S Shiels⁸, Qian Wang⁹, Yuesong Wang⁴, Baoyun Xia⁴, Paolo Boffetta^{10

11}, Paul Brennan¹², Christian C Abnet², Antonia M Calafat⁴, Lanqing Wang⁴, Benjamin C Blount⁴, Neal D Freedman², Cindy M Chang¹

Affiliations

¹ Center for Tobacco Products, Food and Drug Administration, Silver Spring, MD 20993, USA.
² Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
³ Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 1411713135, Iran.
⁴ Division of Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
⁵ Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Liver and Pancreaticobilliary Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 1411713135, Iran.
⁷ Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4917867439, Iran.
⁸ Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
⁹ Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁰ Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA.
¹¹ Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
¹² International Agency for Research on Cancer, 69372 Lyon, France.

Abstract

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.

Keywords: biomarker; lung cancer; tobacco.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Biomarkers
Carcinogens
Case-Control Studies
Cohort Studies
Humans
Lung Neoplasms* / epidemiology
Male
Nitrosamines*
Smokers
Tobacco Products*

Substances

Biomarkers
Carcinogens
Nitrosamines

Abstract

Publication types

MeSH terms

Substances

Grants and funding