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An activity known as methylation (addition of a molecule containing a carbon and 3 hydrogen atoms) of four genes in patients with Stage I non–small cell lung cancer (NSCLC) is associated with an early recurrence. These results were recently published in the New England Journal of Medicine.

Lung cancer remains the leading cause of cancer-related deaths in the United States. The most common type of lung cancer is NSCLC. “Non–small cell” refers to the type of cell within the lung where the cancer originated.

Stage I NSCLC is the earliest stage of lung cancer, where there has been no spread of cancer from the site of origin in the lung. Stage I NSCLC can be cured with surgery alone or with the addition of chemotherapy and/or radiation therapy. Unfortunately, a significant portion of patients with Stage I NSCLC experience a recurrence of their cancer following surgery. The addition of chemotherapy and/or radiation therapy following surgery may improve outcomes for these patients; however, these treatments have high rates of severe side effects. In addition, results regarding the use of chemotherapy and/or radiation therapy following surgery for Stage I NSCLC have not been consistent.

Researchers affiliated with the National Cancer Institute recently conducted a clinical study to evaluate the potential association between methylation in a specific region of seven genes in the original site of cancer and lymph nodes and risk of recurrence. This study included a total of 167 patients with Stage I NSCLC who underwent the surgical removal of their cancer with the intent to cure. Fifty-one patients experienced a cancer recurrence within 40 months following surgery and 116 patients did not experience a cancer recurrence within 40 months following surgery.

  • Methylation within four genes (p16, CDH13, RASSF1A and APC) in the original cancer and lymph nodes with no detectable cancer cells was associated with a significantly increased rate of an early recurrence.
  • Methylation of a certain region (promoter region) of p16 and CDH13 in both the original cancer and mediastinal (middle of the chest) lymph nodes was associated with an approximate 25-fold risk of an early cancer recurrence.

The researchers concluded: “Methylation of the promoter region of the four genes in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence.” If these results are confirmed, methylation of these genes may help to guide a more individualized treatment approach for patients with Stage I NSCLC.

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Patients with Stage I NSCLC may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating these or other markers to help determine risks and individualize therapy for patients with this disease. Two sources of information regarding ongoing clinical trials include the National Cancer Institute ( and

Reference: Brock M, Hooker C, Ota-Machida E, et al. DNA methylation markers and early recurrence in Stage I lung cancer. New England Journal of Medicine. 2008;358:1118-1128.

Related News:

Worse Prognosis for Certain Patients with Stage I Non–Small Cell Lung Cancer (03/17/2008)

Gene Expression Linked with Prognosis in Early-stage Non–Small Cell Lung Cancer (09/17/2007)

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