Canadian doctors are suggesting people with reduced lung function face an increased risk of lung cancer.1
While other experts have implied that this association may exist, "several epidemiological questions regarding this relationship remain unanswered," wrote D.D. Sin, MD, MPH, and his colleagues in the James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research at the University of British Columbia in Canada.
For one thing, since people with reduced lung function are frequently smokers, it's not really known if the reduced function is directly tied to an increased risk of cancer, or if the smoking habit is what boosts the risk, the researchers stressed.
PH and Lung Cancer Relationship
This year alone, it's estimated that more than 172,000 people will be diagnosed with lung cancer, and 163,000 of those will likely die.2 Symptoms include shortness of breath, incessant coughing, wheezing, coughing up blood, chest pain, fever, and weight loss. Smoking, including secondhand smoke, certain environmental influences like radon gas, and inheritance are specific risk factors for the disease.3
While pulmonary hypertension (PH) doesn't normally co-exist in people with lung cancer, case reports have been published involving PH patients in whom a metastatic tumor blocked some of the lung's blood vessels.4,5
PH and lung cancer also share several different pulmonary pathologies, including idiopathic pulmonary fibrosis6 and chronic obstructive pulmonary disease (COPD).7 While the incidence of cancer in people with IPF is relatively rare in the United States,6 the incidence of lung cancer in COPD is "high", experts estimate.8
Lung Function Correlates with Cancer Risk?
In their study, Sin and his colleagues reviewed the results of past research that have examined this possible association. In all, nearly 205,000 patients were included in these studies, who were followed from between nine and 18 years after diagnosis. The investigators used measures of forced expiratory volume, the maximum amount of air that can be exhaled in a given time period, as an indicator of lung function.
Of the patients in the studies reviewed, 6185 eventually died from lung cancer. After considering other potential lung cancer risk factors, such as age, smoking, and body weight, those with the best lung function had the lowest risk of lung cancer, and vice-versa.
Compared to those patients with the best lung function, those with the worst had more than twice the risk of cancer, Sin and his colleagues found. The researchers were also surprised to learn that even those with minimally decreased lung function, including measurements considered within the normal range, had a higher cancer risk—more than one-and-a-half times higher. In all cases, the risk of lung cancer associated with reduced lung function was higher for women. However, the researchers point out that differences in cancer susceptibility between men and women have been controversial.
"Although baseline health status, degree of abnormality in lung function, and length of [patient] follow-up varied considerably between the various cohorts, the associations were remarkably similar," Sin and his team wrote.
Why Does This Apparent Link Exist?
While the reasons that reduced lung function increases the cancer risk weren't explored in this study, the researchers have several theories. It's believed, for example, that inflammation is mainly responsible for the destruction and narrowing of pulmonary tissues that occurs in diseases like IPF and COPD, and which reduces lung function in smokers. This inflammation, Sin and his group speculate, may also play a role in the development of lung cancer since cigarette smoke can ignite an inflammatory reaction in the lungs.
Further, harmful molecules known as free radicals can cause damage in the lungs, and may activate cancer-causing genes in that organ, the researchers speculate. In fact, they theorize that the genes that are responsible for progression of diseases like COPD, as well as lung cancer, may share common origins.
Another theory is that people with reduced lung function "may have an impaired ability to clear inhaled carcinogens from their airways," the research team wrote.
One limitation of the study is that smoking may still have impacted the study's outcome, even though smoking was taken into account when the findings were being analyzed. That is, the patients' smoking habits may have boosted the risk of lung cancer, even though the researchers were looking only at reduced lung function and cancer risk.
Take-Home Message
What's the clinical implication of this study? "In smokers and former smokers, [lung function measurements] may provide criteria beyond age and smoking intensity to identify smokers at high risk for lung cancer," the researchers wrote, in conclusion. "Furthermore, since lung cancer can occur in individuals with only small decreases in [lung function], the traditional boundaries of "normal" [lung function] may need to be modified for screening purposes."
1. Wasswa-Kintu S, Gan WQ, Man SF, Pare PD, Sin DD. Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax 2005 Jul;60(7):570-5.
2. National Center for Chronic Disease Prevention and Health Promotion. Centers for Disease Control and Prevention (CDC). Lung Cancer Statistics. Available at: http://www.cdc.gov/cancer/lung/statistics.htm. Accessed August 4, 2005.
3. National Center for Chronic Disease Prevention and Health Promotion. Centers for Disease Control and Prevention (CDC). Lung Cancer Answers and Questions. Available at: http://www.cdc.gov/cancer/lung/qa.htm#statistics.
4. Nakamura H, Adachi H, Sudoh A et al. Subacute cor pulmonale due to tumor embolism. Intern Med 2004 May;43(5):420-2.
5. Perrin C, Dumon MC, Saint-Paul MC et al. A rare case of severe pulmonary artery hypertension. Thrombosing pulmonary microangiography due to tumor [Translated from French]. Rev Mal Respir 1998 Sep;15(4):545-7.
6. Ma Y, Seneviratne CK, Koss M. Idiopathic pulmonary fibrosis and malignancy. Curr Opin Pulm Med 2001 Sep;7(5):278-82.
7. Lopez-Encuentra A, Astudillo J, Cerezal J, Gonzalez-Aragoness F, Novoa N, Sanchez-Palencia A;Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery. Prognostic value of chronic obstructive pulmonary disease in 2994 cases of lung cancer. Eur J Cardiothorac Surg 2005 Jan;27(1):8-13.
8. Nakayama M, Satoh H, Sekizwa K. Risk of cancers in COPD patients. Chest 2003 May;123(5):1775-6.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
