Associations between history of chronic lung disease and non–small cell lung carcinoma in Maryland: variations by sex and race

Highlights

• Chronic inflammatory lung diseases (COPD and asthma) are associated with NSCLC risk.

• Increase in disease duration is associated with NSCLC risk in women, not in men.

• In never smokers, women, but not men, with asthma are at increased risk for NSCLC.

• Chronic inflammatory lung disease is associated with NSCLC risk in black and white.

Abstract

Purpose

Lung cancer is a multifactorial malignancy for which some risk factors, such as chronic lung diseases, their interactions with smoking, and how they differ by race and sex, are not fully understood. We investigated the associations between chronic inflammatory lung disease and non–small cell lung carcinoma (NSCLC) and how sex and race may affect such associations.

Methods

Using logistic regression, we analyzed 1660 lung cancer cases and 1959 population controls and estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs).

Results

Chronic lung disease was significantly associated with higher odds of having NSCLC in never (AOR = 1.99; 95% CI = 1.19–3.34), former (AOR = 1.68; 95% CI = 1.29–2.20), and current smokers (AOR = 2.40; 95% CI = 1.62–3.57), after adjustment for relevant covariates. For each 5-year increment in chronic lung disease duration, the risk of lung cancer increased only among females (AOR = 1.07; 95% CI = 1.02–1.13). Females, but not males, with asthma were at risk for NSCLC (AOR = 2.08; 95% CI = 1.40–3.10).

Conclusions

This study provides support for chronic lung inflammation as a potential contributing factor to lung cancer risk and possible sex difference in the inflammatory events underlying disease mechanisms.

Introduction

Lung cancer is the leading cause of cancer-related mortality worldwide and in the United States [1], [2], [3]. There are two predominant types: small cell lung carcinoma and non–small cell lung carcinoma (NSCLC); the latter is the most common type (85%–90% of all cases) [4]. Differences in incidence and mortality exist by race and sex. In the United States, age-adjusted incidence and mortality rates of lung cancer are significantly higher in black than in white men, but comparable between black and white women [3], [5], [6]. Cigarette smoking is a well-established risk factor for developing lung cancer [7]; however, approximately 25% of all lung cancer cases are not attributable to smoking [8], [9], and 10%–15% of these cancer deaths occur in never smokers [10]. Other established risk factors for lung cancer, including environmental tobacco smoke (ETS), radon gas, occupational exposures to carcinogens, air pollution, and genetic susceptibility [11], [12], failed to explain all of its incidence, particularly in never smokers [9], [10].

Lung cancer in never smokers occurs disproportionately in women [13], [14], has better response to targeted therapy [15], and its incidence is higher in non-whites [16]. These unique characteristics suggest that it may be a different disease from smoking-related lung cancer [9], [15]. One potential risk factor is chronic inflammation, which can lead to DNA damage, mutations, and ultimately cell growth and proliferation [17], especially among never smokers [18], [19], [20], [21], [22]. Both prospective and retrospective studies have found a positive association between chronic obstructive pulmonary disease (COPD) and lung cancer risk in never smokers [18], [19], [23], [24], whereas others found positive associations with other lung diseases such as asthma, tuberculosis, and pneumonia [18]. Many of these studies did not explore sex- and/or race-specific associations, and some studies had small sample size or did not carefully examine the potential interplay of chronic lung diseases and tobacco exposures.

To address these gaps in knowledge, we analyzed data from the Maryland lung cancer study. We assessed the associations between NSCLC risk and history of chronic lung disease (defined as history of chronic bronchitis, COPD, emphysema, or asthma) and its duration (i.e., time since the participants' diagnoses), and how sex and race affect such associations, in the presence or absence of smoking.