CARET's keys to earlier detection

Nearly 90 percent of people who develop lung cancer are smokers, yet only about 10 percent of lifetime smokers will develop the disease. A recent study from the Public Health Sciences Division provides insight into one of the factors that may put a subset of tobacco users at increased risk of lung cancer.

In a study of more than 17,000 men and women, the majority of whom were heavy smokers, Dr. Alyson Littman and colleagues found that those who had been diagnosed with chronic bronchitis or emphysema (CB/E) prior to their cancer diagnosis were about 30 percent more likely to develop lung cancer than those without such a diagnosis. The risk associated with CB/E for a form of the disease known as squamous-cell carcinoma was even higher, about 50 percent.

The study, published in the October issue of Cancer Causes and Control, is the most comprehensive analysis to date on the association between prior lung diseases and lung cancer in heavy smokers. Co-authors included Fred Hutchinson investigators Drs. Mark Thornquist, Emily White, Gary Goodman and Thomas Vaughan, and Dr. Lisa Jackson of the Center for Health Studies at Group Health Cooperative.

The findings — and other research of this kind — are important because they may help doctors identify smokers who are most likely to get lung cancer. Those individuals may benefit from prevention strategies or screening tests that could allow the disease to be diagnosed at an early stage, when it is more likely to be treatable.

"Part of what makes lung cancer so deadly is that it's typically detected when it's advanced," said Littman, who conducted the analysis as part of her doctoral research with Vaughan, head of the center's epidemiology program. "Of course, the best lung-cancer prevention strategy is for people to quit smoking. But if it were possible to identify high-risk individuals within a group that is already at high risk due to smoking, it may be possible to target screening to those people to allow for earlier cancer detection."

Screening for lung cancer, such as by spiral computed tomography (CT) scanning, has been controversial because of its expense and lack of comprehensive studies. Research is underway at many institutions, including Fred Hutchinson, to identify protein markers in blood serum or sputum that signify early onset of lung cancer.

CARET study

In the current study, researchers analyzed information on non-cancerous lung diseases among participants in the Carotene and Retinol Efficacy Trial (CARET), a randomized prevention trial begun in 1985 that evaluated whether beta-carotene and vitamin A supplements reduce the risk of lung cancer in heavy smokers and asbestos-exposed workers. The intervention portion of the trial ended early, in 1996, when it was discovered that the supplements did not prevent, and in fact increased the risk of lung cancer in these high-risk groups.

At the start of the CARET study, participants provided information about whether they had ever been diagnosed with certain medical conditions, including five lung diseases: asbestosis, asthma, chronic bronchitis or emphysema, pneumonia and tuberculosis.

Through June 2002, 1,028 cases of lung cancer were diagnosed among the 17,698 participants who were followed. The researchers used statistical analyses to determine whether prior lung diseases were associated with the development of different forms of lung cancer among the participants.

The median age of participants at the start of the study was 58 years, and the average "pack-years" of smoking were 44 — the equivalent of a pack a day for 44 years or two packs a day for 22 years.

Researchers found that lung-cancer rates increased with age. Among the noncancerous lung diseases examined, having had CB/E was the only condition found to be associated with a significantly increased likelihood of developing lung cancer. Overall, those with CB/E were 30 percent more likely to develop lung cancer than those without a history of CB/E; the risk was 50 percent greater for squamous cell carcinoma among those with CB/E compared to those without such a history. The association was strongest among those diagnosed with lung cancer before age 65.

Chronic bronchitis and emphysema, conditions generally brought on by smoking, are characterized by ongoing inflammation and obstruction of the airways from the windpipe to the lungs.

Although the study did not address whether CB/E actually causes lung cancer the researchers point out two possible ways in which this could occur. Because CB/E is associated with obstruction of the airways, cancer-promoting inhalants — such as from cigarette smoke — could accumulate and cause further damage to lung tissue. In addition, inflammation, which triggers a cycle of tissue injury and repair, has been associated with increased cancer risk of many types. Increased turnover of cells due to injury or inflammation increases the likelihood of genetic errors being introduced into DNA, some of which could predispose cells to become cancerous.