Researchers at Fox Chase Cancer Center have found a new link between oestrogen and lung cancer among never-smokers and smokers: that human lungs can metabolize the hormone oestrogen, yielding a carcinogenic derivative.

Oestrogen has an established link to increased risk of breast and endometrial cancer, and in a previous study, this same group of researchers found oestrogen 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 tumour 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 oestrogen metabolite varies with race/ethnicity, sex, and smoking status.

“While oestrogen 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” oestrogen 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” oestrogen 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” oestrogen 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.