Shortened telomere length in peripheral blood leukocytes of patients with lung cancer, chronic obstructive pulmonary disease in a high indoor air pollution region in China

Highlights

• Telomere length shortened in lung cancer cases in coal smoke exposure population.

• Telomere length shortened in COPD cases in coal smoke exposure population.

• Coal smoke exposure levels affected Telomere length.

• Lung function was associated with telomere length and environmental exposure.

Abstract

Lung cancer and chronic obstructive pulmonary disease (COPD) are closely linked diseases. In Xuanwei, China, the extremely high incidence and mortality rates of lung cancer and COPD are associated with exposure to household smoky coal burning. Previous studies found that telomere length was related to lung disease. The objective of this study is to investigate the relationship of peripheral blood leukocyte telomere length to both lung cancer and COPD, as well as indoor coal smoke exposure in Xuanwei. We measured telomere length using quantitative polymerase chain reaction (qPCR) in peripheral blood leukocytes of 216 lung cancer patients, 296 COPD patients, and 426 healthy controls from Xuanwei. The telomere length ratios (mean ± SD) in patients with lung cancer (0.76 ± 0.35) and COPD (0.81 ± 0.35) were significantly shorter than in that of controls (0.95 ± 0.39). Individuals with the shortest tertile telomere length had 3.90- and 4.54-fold increased risks of lung cancer and COPD, respectively, compared with individuals with the longest tertile telomere length. No correlation was found between telomere length and pack-years of smoking. In healthy subjects, coal smoke exposure level affected telomere length. Lung function was positively and negatively associated with telomere length and environmental exposure, respectively, when combination the control and COPD groups. The result suggests that shortened telomere length in peripheral blood leukocytes was associated with lung cancer and COPD and might be affected by coal smoke exposure level in Xuanwei. Whether variation in telomere length caused by environmental exposure has a role in lung cancer and COPD development and exacerbation needs further research.

Introduction

Lung cancer and chronic obstructive pulmonary disease (COPD) cause a major health care burden and high mortality among respiratory diseases. Worldwide, lung cancer is the most common and deadliest cancer, representing up to 11.6% of total new cases and 18.4% of all cancer deaths in 2018 [1]. According to The Global Burden of Disease Study 2015, COPD was the third leading cause of death, with an estimated 174 million cases worldwide [2,3]. With many common underlying predispositions and disease mechanisms, lung cancer and COPD are considered to be closely related diseases [4]. Further, the presence of COPD has been proved to be an independent risk factor for lung cancer, and COPD patients were at twice greater risk of lung cancer development [5,6]. With the exception of smoking, exposure to air pollutants is also the primary risk factors for COPD and lung cancer [7,8].

Xuanwei City has the highest incidence and mortality of lung cancer and twice the national average prevalence rates of COPD in China, which has been attributed to the high prevalence of tobacco smoking and serious environmental exposures to indoor air pollution from the household use of smoky coal [9,10]. Indeed, smoky coal combustion generates substantial polycyclic aromatic hydrocarbons (PAHs), mineralogical compositions, and respirable particles, which are strongly related to the development of lung cancer and COPD [11,12]. Xuanwei City provides a typical model in which to assess lung disease susceptibility, pathogenesis, and etiology related to environmental factors in a coal smoke exposure population.

Telomeres consist of short DNA repeats and associated proteins located at the ends of chromosomes that play important roles in maintaining genomic integrity and stability. Generally, telomere length is regarded as a biomarker of aging, and telomeres shorten during DNA replication and cell division in somatic cells. This process may be accelerated by cumulative oxidative stress and inflammation [13,14]. Telomere length in peripheral blood leukocytes is often used as a surrogate for telomere length in other tissues due to its convenience. Telomeres are linked to a variety of lung diseases, including emphysema, idiopathic pulmonary fibrosis, COPD, and lung cancer [15]. Several studies have demonstrated that patients with COPD have shorter telomere length in circulating leukocytes [16,17]. However, prospective and retrospective studies have shown inconsistent results about the relationship between peripheral leukocyte telomere length and lung cancer risk [18,19]. Additionally, exposure to air pollution such as particulate matter (PM), PAHs, and black carbon, has been reported to affect leukocyte telomere length [20,21]. Thus, whether the high incidence of lung cancer and COPD is associated with variation in telomere length caused by environmental exposure is a subject worthy of study.

In this study, we investigated the circulating leukocyte telomere length in patients with lung cancer and COPD from Xuanwei to explore the relationship between telomere length and both lung cancer and COPD, as well as the effects of indoor air pollution exposure on telomere length.