Gene Profiling Plus Bronchoscopy Improves Lung Cancer Screening

Researchers have improved the detection rate for lung cancer in smokers and former smokers suspected of having the disease by profiling gene activity in cells that were obtained from the airway during fiberoptic bronchoscopies. Dr. Avrum Spira of the Boston University School of Medicine described the experimental strategy and findings from their research at the AACR annual meeting.

A bronchoscopy is often used as the first tool for diagnosing the disease, but the test is accurate in only about half the cases. By adding the gene profiling to the bronchoscopy, the researchers detected lung cancer accurately in more than 90 percent of cases in their study population.

The study included individuals who were scheduled to have a bronchoscopy to screen for the disease, but, in addition, the researchers profiled the activity of 80 genes in the airway cells collected during the bronchoscopies. In this procedure, a tube the size of a pencil is passed into the lungs to collect cells from the walls of the airways. The researchers noted that the gene signature was better than bronchoscopy at detecting the disease in its early stages, when treatment is likely to be most effective.

In the United States, an estimated 75,000 cases of lung cancer are not detected as early as they potentially could be because they are missed by bronchoscopies, according to Dr. Spira. To address this problem, his team identified the set of 80 genes that can be used to accurately distinguish smokers and former smokers who have the disease from those who do not. The gene signature is not yet ready for use in the clinic, but Dr. Spira expects to have a refined version ready within the next 2 years.

Long-Term Smoking Cessation May Repair Lung Damage

Long-term smoking cessation increases the blood levels of an important anti-inflammatory protein CC10 that several studies have suggested may play a role in combating the development of lung cancer, NCI researchers reported at the AACR annual meeting. The findings, says the study's leader, Dr. Jiping Chen, a cancer prevention fellow at NCI, provides some important insights about smoking cessation's impact at the molecular level.

"This is good news for former smokers," Dr. Chen says. "It provides more evidence that quitting smoking can undo some of the damage to the lung resulting from tobacco exposure."

The researchers measured levels of CC10 in 81 current and 23 former smokers with precancerous lesions called bronchial dysplasia. All of the participants had been part of a lung cancer chemoprevention trial. Levels of CC10 were measured in blood and bronchoalveolar lavage samples, which are collected by injecting sterile saline into the lungs with a fiberoptic scope and then removing samples of the resulting fluid.

CC10 is known to protect the bronchial lining from oxidative and inflammatory insults. Several studies have shown that its expression is decreased in smokers; laboratory and animal model studies conducted at NCI also have shown that CC10 is downregulated in the earliest stages of cancer development, and that increasing its expression can slow tumor development.

In this study, CC10 levels in the blood samples of former smokers were statistically significantly higher than in current smokers; CC10 levels were also higher in the lavage samples of former smokers, but the difference did not achieve statistical significance. The average length of smoking cessation in the former-smokers group was 7 years.

Further studies are needed to elucidate CC10's role in lung cancer, Dr. Chen cautions, such as a large cohort study that could "prospectively determine whether CC10 is associated with lung cancer incidence."

Rituximab Shows Promise for Graft-Versus-Host Disease

A phase I-II study of rituximab, an anti-B-cell monoclonal antibody, among patients who suffer from chronic graft-versus-host disease (GVHD), a deadly posttransplant autoimmune illness, reduced symptoms in 70 percent of participants after 1 year of follow-up. Of the 21 patients who participated, 2 lost all signs of the disease. The study results appeared online in Blood on March 21.

GVHD occurs frequently in patients who receive donor tissues, such as leukemia patients who receive bone marrow transplants. Corticosteroid therapy and calcineurin inhibitors can be used to treat it, but they are toxic, not always effective, and had already failed among participants in this study.

The trial regimen included 4 initial weeks of rituximab at a dose of 375 mg/m² per week, with subsequent courses offered to those who did not initially respond. When symptoms were limited to the skin and musculoskeletal system, rituximab showed the greatest result - the median body surface area affected dropped from 42 to 20 percent in sclerodermatous cutaneous GVHD cases, and from 19.5 to 3 percent in lichenoid cutaneous GVHD cases. Patients with rheumatologic symptoms saw their pain and fatigue fall significantly after two treatment cycles and continue to decrease thereafter.

Until recently, it was thought that GVHD is mediated by T cells in the donor tissue, but the authors note that these results support their previous work, indicating B cells may also be involved. "The use of monoclonal anti-B-cell therapy should be tested as a prophylactic and initial treatment strategy," they write.

Smoking, Drinking, and Gender Linked to Colorectal Cancer

The risk of developing advanced colorectal cancer at a younger age is greater among men, and also among people who smoke or drink, according to a retrospective American population study published in the March 27 Archives of Internal Medicine. The findings could influence strategies for screening to detect the second most lethal cancer.

The researchers used self-reported data from an HMO database to classify 166,172 colorectal cancer patients according to smoking and drinking history (former, current, or never). Current users of both substances were an average of 7.8 years younger when diagnosed than those who had never used either, with the effect more pronounced among men. Current smokers who never drank fared slightly better; the age at diagnosis was reduced by 6.3 years in women, compared with 3.7 years in men. Among all patients, drinking raised risk by 19 percent, smoking by 16 percent.

Screening for colorectal cancer is especially important because detectable symptoms usually mean advanced disease and poor prognosis. Screening is currently recommended at age 50, but these findings suggest that those who smoke and drink would benefit from earlier screening, wrote study leader Dr. Anna L. Zisman and colleagues from Northwestern University.