Gene Environment Interactions in Women With Breast and Secondary Lung Cancer
Annual summary rept. 1 Jul 2003-30 Jun 2006
GEORGETOWN UNIV WASHINGTON DC
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Women with breast cancer are at increased risk for developing a second primary tumor in the lung. There may be a greater risk for women who receive radiotherapy and smoke. 110 cases with breast and lung cancer and 123 controls with breast cancer only were collected through the Swedish Cancer Registry in Stockholm, Sweden. Two pathologists jointly conducted a review to verify the registered primary status of the lung tumors. About 25 of lung tumors could not be confirmed as primary and these cases were excluded from data analysis. Four possible markers of susceptibility to lung cancer after breast cancer were examined p53 mutations, p16 and Ecad methylation, and Estrogen Receptor Alpha ERA. 81 of control breast tumors, 73 of case breast tumors, and 2 of case lung tumors were positive for ERA by immunohistochemistry. We found a decreased risk of lung cancer diagnosed less than ten years after breast cancer associated with strongly positive ERA expression in breast tumors OR 0.08 CI 0.008-0.5. 2 of control breast tumors, 4 of case breast tumors, and 15 of case lung tumors were positive for p16 promoter methylation. No breast tumors and 11 of case lung tumors were positive for Ecad promoter methylation. Methylation of p16 or Ecad in lung tumors was associated with radiotherapy and ipsilateral lung tumors diagnosed greater than ten years after breast cancer p0.03. 4 of control breast tumors, 5 of case breast tumors, and 21 of case lung tumors were positive for p53 mutations. Though limited by small sample size, this project will be a unique addition to the study of primary lung cancer after breast cancer. We found that as much as 25 of lung tumors registered as primary may actually be metastases, that ERA positive breast tumors are associated with a decreased risk of lung cancer diagnosed less than ten years after breast cancer, and that methylation of p16 or Ecad is associated with lung tumors characteristic of radiationinduced cancer.
- Medicine and Medical Research
- Stress Physiology