Abstract

Simple SummaryLung cancer is currently the most common cancer worldwide. This study investigates whether visit-to-visit variability in metabolic parameters is associated with lung cancer risk. We found that a high variability in fasting blood glucose, systolic blood pressure, total cholesterol, and body weight were each associated with increased risk of lung cancer. A higher number of high-variability parameters were also associated with increased lung cancer risk. Further research is needed to examine whether reducing variability can lead to decreased lung cancer risk.We investigated whether visit-to-visit variability in metabolic parameters is associated with lung cancer risk. We used nationally representative data from the Korean National Health Insurance System, and 8,011,209 lung-cancer-free subjects who underwent over three health examinations from 2005 to 2010 were followed until 2017. Variability of fasting blood glucose, total cholesterol, systolic blood pressure, and body weight were measured by the variability independent of the mean, assessed by quartiles. There were 44,982 lung cancer events. The hazard ratio (HR) and 95% confidence interval (CI) for lung cancer risk was 1.07 (1.04, 1.10) for fasting blood glucose in the highest quartile, 1.08 (1.05, 1.10) for systolic blood pressure, 1.04 (1.01, 1.07) for weight, and 1.11 (1.08, 1.14) for total cholesterol. When comparing ≥3 vs. 0 high-variability metabolic parameters, the HR for lung cancer was 1.18 (95% CI, 1.14, 1.22). However, while ≥3 high-variability parameters showed an increased lung cancer risk in men (HR 1.26, 95% CI 1.21, 1.31), women did not show increased risk (HR 0.99, 95% CI 0.92, 1.06). High variability in each metabolic parameter, and a higher number of high-variability parameters, were associated with increased lung cancer risk.

Highlights

  • Lung cancer is currently the most commonly diagnosed cancer worldwide, and the leading cause of deaths due to cancer, according to global cancer statistics [1]

  • The risk of lung cancer was highest in the highest variability independent of the mean (VIM) quartile group, compared with the lowest quartile, even after adjusting for baseline metabolic parameters (Table 2)

  • Our study is the first to suggest that a high variability of FBG, SBP, and TC may be associated with increased lung cancer risk

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Summary

Introduction

Lung cancer is currently the most commonly diagnosed cancer worldwide, and the leading cause of deaths due to cancer, according to global cancer statistics [1]. Tobacco smoking is known as the largest risk factor for lung carcinogenesis, but according to estimates by the International Agency for Research on Cancer, approximately 20% of lung cancer cases occur in never-smokers [1]. Previous studies have suggested associations between lung cancer risk and metabolic parameters such as diabetes mellitus [4], obesity [5], high blood pressure [6], and plasma lipid levels [7]. Possible mechanisms include oxidative stress and inflammation [8], which may lead to reduced intracellular antioxidants in favor of lung carcinogenesis, and increased reactive oxygen species, which may damage deoxyribonucleic acid (DNA) through oxidation or impaired DNA repair [9]. Alterations in insulin-like growth factors [10], and adipokines [11] are suggested as potential mechanisms for these associations

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