||5R01CA092705-05 Interpret this number
||Molecular Epidemiology of Secondary Lung Cancer
Several studies indicate that women with breast cancer who undergo radiotherapy are susceptible to secondary lung
cancer, whether they are smokers or nonsmokers. However, all studies to date have methodological limitations and
have been small. Also, none have used molecular markers, which can improve exposure assessments or elucidate
mediating mechanisms. Over time, radiotherapy methods have changed and doses to the lung have lessened. On the
other hand, prevalence of smoking has increased among women in the western world. The identification of lung cancer
risk is important in the context of the debates for benefits of radiation therapy in good prognosis tumors or older
women. Thus, a study of breast and secondary lung cancer is needed to improve dosimetry assessments for radiation-
induced lung cancer, with and without an interactive effect of smoking. Also, studying a unique population of women
who have had both breast and lung cancer can provide new insights into carcinogeneis and cancer risk. In order to do
this, we are proposing a population-based study using the Swedish Cancer Registry (SCR) and determination of
radiation doses to the whole lung and side of the lung where the tumor subsequently develops. Reliable smoking data
will be available. Our specific aims are to: 1) determine risk factors for secondary lung cancer in women treated with
radiotherapy for breast cancer using complementary nested case-control and case-only study designs (n=559 cases and
559 matched controls); 2) to determine p53 inactivation pathways, (i.e., mutational spectra and loss of heterozygosity)
in lung tumors of women with a prior history of breast cancer (n=402) and; 3) to determine the frequency of p53
inactivation pathways in breast tumors of women who did and did not develop lung cancer, and compare them to the
frequency of p53 inactivation pathways in the lung tumors (n=342 cases and 342 controls). The first aim will allow us
to identify risks. The second aim will provide information about the mechanistic relationship of radiotherapy to lung
cancer and may identify a unique spectrum for radiation-related lung cancer. The third aim considers the combined
occurrence of breast and lung cancer in a woman as phenotype of susceptibility for multiple primary cases. This study
provides unique opportunities. Using the SCR and the unparalleled ability to obtain tissue blocks dating back to the
1950's, we can provide new data to understand risk in the context of molecular markers, especially because we will be
able to retrieve the tumor blocks from both the breast and lung cancer from the same women.
Lombardi Cancer Center Karolinska Institute
Georgetown University Medical Center Department of Medical Epidemiology
The Research Building Box 381
3970 Reservoir Road NW 19179 Stockholm
Washington, DC 20007-2197
KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in
Start with Principal Investigator. List all other key personnel in alphabetical order, last name first.
Dr. Peter Shields Georgetown University Medical Center, Washington, DC
Dr. Per Hall Karolinska Institute, Sweden
Dr. Giovanna Gagliardi Karolinska Institute, Sweden
Dr. Balgit Singh Georgetown University Medical Center, Washington, DC
Dr. Bassam Haddad Georgetown University Medical Center, Washington, DC
Dr. Tim Jorgensen Georgetown University Medical Center, Washington, DC
Dr. Frederik Granath Karolinska Institute, Sweden
Dr. Melissa Bondy MD Anderson Cancer Center, Houston, TX
Dr. Jo Freudenheim SUNY, University at Buffalo, Buffalo, NY
Dr. Lois Travis National Cancer Institute, NIH, Bethesda, MD
Dr. Goran Pershagen Karolinska Institute, Sweden
Disclosure Permission Statement. Applicable to SBIR/STTR Only. See instructions.  Yes  No
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Role on Project
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¿ Principal Investigator/Program Director (Last, first, middle): Shields, Peter G.
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TABLE OF CONTENTS
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