Non-malignant lung diseases and the risk of lung cancer:  A Meta Analysis

Michael J. Kelo

Background: Lung cancer accounts for 28% of all cancer deaths and many more Americans now die from lung cancer than breast, prostate, and colorectal cancer combined. Although there is a well-established relationship between lung cancer and smoking, there is disagreement in the scientific literature as to whether exposure to prior lung diseases results in an increased risk of lung cancer later in life. Since the 1960’s, studies have been conducted to investigate the effect of emphysema, chronic bronchitis, tuberculosis (TB), pneumonia, and asthma as causative factors for lung cancer. To better delineate the role of these disease states in the risk for lung cancer, many studies simultaneously investigated the impact of smoking and environmental exposures as additional factors for developing lung cancer. We conducted a meta-analysis of studies that investigated the role of emphysema, chronic bronchitis, tuberculosis, pneumonia, and/or asthma as causative factors in the risk of developing lung cancer to further understand the potential relationship between prior lung diseases and lung cancer.

Methods: A computerized search of the English language published studies was conducted cross-referencing each of the five non-malignant lung diseases with lung cancer. Studies published from January 1960 through January 2001 were identified using the MEDLINEâ and PUBMEDâ databases. Inclusion criteria were developed which determined the acceptance of 22 studies into the final analysis. Analyses were conducted separately using each of the five non-malignant lung diseases as the effect variable and lung cancer as the outcome variable. Additional analyses were conducted to investigate whether gender, continent of study, and the type of lung cancer pathology studied altered the effect size. Each non-malignant disease and lung cancer category was further scrutinized using sensitivity analysis and influence analysis. Studies were also assessed using a weighted quality score based on five study characteristics. Results: All effect sizes were estimated using odds ratios (OR) and 95% confidence intervals (CI). Statistically significant risks for lung cancer from emphysema for all males and females was OR= 1.77 (1.34, 2.20). The risk for lung cancer from emphysema for Asian and American women combined was OR= 1.91 (1.22, 2.60) while the risk for American women was even greater at OR= 2.73 (1.48, 4.01). Former smokers and non-smoking women with emphysema showed no statistically significant risk for the development of lung cancer. Emphysema and type of cancer pathology was significant for adenocarcinoma (ADC) OR= 2.26 (1.27, 3.15) but not for non-ADC. Chronic bronchitis and risk of lung cancer was not statistically significant for Americans OR= 1.35 (0.98, 1.68) but Asians had substantially increased risk at OR= 2.18 (1.46, 2.90). Asian males and females who had TB had a greater risk of any lung cancer studied OR= 1.47 (1.13, 1.79) versus Americans. TB and lung cancer risk was greatest for Asians with non-ADC OR= 2.25 (1.31, 3.18) while no group had a statistically significant risk for ADC. Asians and Americans with a history of pneumonia had a statistically significant risk for all categories of lung cancer studied. Smokers with pneumonia had an increased risk of lung cancer, OR= 4.14 (1.71, 6.56). In the studies that analyzed asthma and lung cancer, only American studies allowed for gender analysis. Females had no statistically significant increase in risk of lung cancer for any of the asthma factors analyzed but the data indicated that males likely have an increased risk. Conclusions: These results showed an increased risk of lung cancer for individuals who previously had emphysema, chronic bronchitis, TB or pneumonia. There was no evidence to support the notion that asthma results in an increased risk of lung cancer for females while males likely have an increased risk. The results support the notion that preventing non-malignant lung diseases earlier in life may likely reduce the risk of getting lung cancer later in life.