Relationship Between Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol and Lung Cancer Risk in the General Population: A Community-Based Prospective Cohort Study.

Eun Young Park,Do-Hoon Lee,Jin-Kyoung Oh,Min Kyung Lim

doi:10.3389/fonc.2021.611674

Abstract

No published studies have prospectively evaluated the association between urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels and lung cancer risk in the general population. Here, we conducted a prospective community-based cohort study in the Republic of Korea to evaluate the relationship between urinary NNAL levels and lung cancer risk using prediagnostic urine samples. This prospective cohort study was based on the Korean National Cancer Center Community Cohort. During the follow-up period, 173 primary lung cancer cases were identified. Total urinary NNAL levels were measured by liquid chromatography-tandem mass spectrometry, and data were analyzed using multivariable Cox proportional hazards regression models. The risk of lung cancer was significantly increased per unit of natural log-transformed urinary NNAL (HR, 1.27; 95% CI, 1.09–1.48), after adjusting for age, region, entry year into the cohort, education achievement, alcohol consumption status, BMI, smoking status, and urinary cotinine levels. Cox proportional-hazards models with NNAL quartiles also showed positive dose-response relationships with risk of lung cancer. A significantly increased risk of lung cancer was found in the fourth quartile of urinary NNAL levels (HR, 3.27; 95% CI, 1.37–7.79, P for trend < 0.01). After stratification with sex, the significant association remained in only men. Urinary NNAL levels are associated with the risk of lung cancer in the general population, and this association is independent from the quantification of cigarette smoking and nicotine uptake.

Highlights

Lung cancer is the leading cause of cancer mortality and one of the most commonly diagnosed cancers in Korea and worldwide [1, 2]
In the nested case-control study of lung cancer within the Shanghai Cohort, total urinary NNAL was associated with lung cancer risk in people with the highest tertile (≥0.210 pmol/mg creatinine [43.94 pg/mg creatinine]) compared with those in lowest tertile (≤0.105 pmol/mg creatinine [21.97 pg/mg creatinine]), after adjustment for total urinary cotinine levels and smoking intensity and duration [9]
The lung cancer risk associated with NNAL in this study was estimated to be relatively higher than those from other previous studies [9, 13, 14], as approximately half of the study participants were self-reported nonsmokers, who have lower level of NNAL than smokers who used as reference group of other previous studies, and they were mostly categorized as a reference group in the present study

Summary

Introduction

Lung cancer is the leading cause of cancer mortality and one of the most commonly diagnosed cancers in Korea and worldwide [1, 2]. The carcinogenicity of occupational and environmental exposure of some factors such as radon, asbestos, silica, polycyclic aromatic hydrocarbons, and air pollution has been well identified for lung cancer [3], contribution of long-term cigarette smoking is an established causal factor for lung cancer and contributes to approximately 90% of lung cancer mortality [4]. Total urinary NNAL has an advantage over other smoking-related biomarkers (e.g., urinary cotinine) for epidemiological studies due to its relatively long halflife (i.e., 10 days to 3 weeks) [8, 9]. This measure is a sensitive and specific biomarker of exposure to secondhand smoke [10, 11]

Methods

Results

Conclusion