Estrogen Metabolism in the Lung May Increase Lung Cancer Risk

Margie Clapper PhD, deputy scientific director and co-leader of the Cancer Prevention and Control Program
Margie Clapper PhD, deputy scientific director and co-leader of the Cancer Prevention and Control Program

PHILADELPHIA (December 7, 2017) – Researchers at Fox Chase Cancer Center have found a new link between estrogen and lung cancer among never-smokers and smokers: that human lungs can metabolize the hormone estrogen, yielding a carcinogenic derivative.

Estrogen has an established link to increased risk of breast and endometrial cancer, and in a previous study, this same group of researchers found estrogen metabolites within the lungs of mice, some of which are known to have the potential to cause cancer. The new study is the first to demonstrate the ability of the human lung to convert the hormone into numerous metabolites. This process is accelerated as the tumor forms.  This discovery appears in the journal Oncotarget.

“Our finding underscores the importance of understanding and treating lung cancer as a disease with more than one cause,” said Margie Clapper PhD, deputy scientific director and co-leader of the Cancer Prevention and Control Program at Fox Chase and senior author of the study. “While it is true that smoking tobacco is the top risk factor for lung cancer, a substantial number of people receive a diagnosis despite having never smoked.”


Jing Peng, PhD, research associate at Fox Chase and lead author of the study, said the research also revealed that production of the carcinogenic estrogen metabolite varies with race/ethnicity, sex, and smoking status.

“While estrogen metabolites were detected within the lungs of both men and women, men had lower levels, as expected. Chinese-American women produced more of the “bad” estrogen than non-Hispanic white women, which makes sense, as Chinese never-smoking women have much higher rates of lung cancer than never-smoking European and Caucasian women,” Peng said.

Moving forward, the researchers will determine whether blocking the pathways that allow the production of “bad” estrogen metabolites in the lung will reduce the incidence of cancer.

“These findings have many clinical implications and provide exciting new insight into how we may be able to prevent this devastating disease,” Clapper said. “We’ve already begun looking at whether the level of the “bad” estrogen can serve as a marker of cancer risk or prognosis.”

Worldwide, about 15 percent of men and 50 percent of women with lung cancer have never smoked.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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