There is increasing evidence that women are more susceptible to lung cancer than men, particularly if they smoke. A Roswell Park Comprehensive Cancer Center research team led by Christine Ambrosone, PhD, Chair of Cancer Prevention and Control, recently added support to the estrogen hypothesis of lung cancer development by identifying a link among smoking, sex, and hormones in patients with non-small cell lung cancer (NSCLC). Their findings have been published online ahead of print in the Journal of the National Cancer Institute.

The team collected tumor samples from 813 men and women with NSCLC in an attempt to identify the association between both smoking status and sex and the expression of different hormone receptors in the lung. The researchers found that the expression of estrogen receptor beta (ER-β), a hormone receptor that is known to inhibit tumor growth, was lower in women than in men, which supports the idea that women are in fact more susceptible to lung cancer. Levels of this hormone receptor were particularly low in postmenopausal women and in those who had never used hormone therapy, suggesting that a decrease in the amount of circulating estrogen could be responsible. Other studies have suggested that expression of ER-β in NSCLC patients is lower in women than men, but the Roswell Park study is the first to confirm this sex difference.

The researchers also found that smoking influences hormone expression in both men and women. Lung tumors of smokers had higher levels of estrogen receptor alpha (ER-α), which is known to promote tumor growth, than the tumors of nonsmokers. Smokers also tended to have lower expression of progesterone receptors, which contributes to a poorer prognosis, because progesterone can inhibit the growth of cancer cells.

“Our findings suggest that smoking increases an individual’s cancer risk by disrupting important hormone pathways,” notes first author Ting-Yuan “David” Cheng, PhD, assistant professor of oncology with the Roswell Park Cancer Prevention and Control team, who also holds a faculty appointment at the University of Florida. “Smoking cessation is, therefore, important for both women and men in order to preserve the integrity of hormone receptors.”