Study Suggests Smoking Is Associated with Chromosome Loss

A study of lung cancer patients led by Duke University investigators and funded by the V Foundation showed chromosome loss in nearly half of those classified as “heavy smokers.”

Researchers found that a portion of chromosome 11 was missing in 43% of patients who were heavy smokers. Heavy smokers, for the purposes of the study, were people who had smoked about 40 pack-years. (The number of packs a day multiplied by the number of years smoked gives the amount smoked in pack-years.)

The chromosome deletion indicated more aggressive tumors, with patients living only about half as long as their counterparts who did not have the chromosome loss, says Dr. Gerold Bepler, assistant professor of medicine at Duke and chief of hematology/oncology services at the Veterans Administration Medical Center in Durham, North Carolina. The median survival for patients without the chromosome loss was 42 months, compared to 25 months for patients in whom the loss occurred.

Bepler says the chromosome loss was more apparent in male than in female smokers.

No chromosome loss was found in lung cancer patients who were nonsmokers. “The striking finding about this study, in my opinion, is the strong association with smoking,” Bepler says. While further studies need to be done, the finding could lead to more aggressive treatments for lung cancer patients who demonstrate the chromosome loss, he says.

New Prognostic Marker

In Notes, a publication from the Duke Comprehensive Cancer Center, Bepler says the missing length of chromosome may serve as a prognostic molecular marker to physicians, indicating an out-of-control, fast-growing tumor that needs intensive treatment measures.

He says previous studies showed some mutations in tumor-suppressor genes in smokers, but did not indicate a change this extensive.

“This study does not indicate a single-based change,” he says. “We are talking about a big break in the chromosome. A whole gap, an entire big piece is missing. A person who has lung cancer and has this loss has a more aggressive tumor and probably will not live as long as a patient with lung cancer who does not have this loss.” He says at least one out of three smokers with lung cancer is likely to have the missing piece.

The research team looked at the LOH11B (LOH = loss of heterozygosity) lung cancer region on chromosome 11. The region does not cause lung cancer, but simply indicates a poorer prognosis for patients who have lost it. It contains a gene responsible for lung cancer malignancy, separate from the usual metastatic potential of lung cancer.

Far-Reaching Effects

The break in the chromosome occurred next to the telomere. Such losses are usually seen in association with ionizing radiation, such as high radiation doses, Bepler says. The short arm of chromosome 11 (11p) is also altered in breast and bladder cancer and in the childhood tumor rhabdomyosarcoma and Wilms’ tumor, he adds.

In his search for a gene that causes lung cancer, he is concentrating on another portion of chromosome 11, the LOH11A region. He says the research team came across the chromosome break in their search for a lung cancer gene.

“The search for a gene is very complex, since you will find several regions that are involved in the development of lung cancer,” he says. “One region might set up the cell to become cancer. Another might turn the cell into adenocarcinoma versus squamous cell carcinoma. Another might be important in how a patient responds to treatment. Another might show how aggressive the cancer is and how fast it is metastasizing. This particular region shows how aggressive the cancer is.”

Details of this study were published in the May issue of Cancer Epidemiology, Biomarkers & Prevention.