Estrogen Plays a Key Role in Lung Cancer Development
A link between hormones and smoking may provide insight as to why women are more likely to develop non–small cell lung cancer compared with men.
Previous research shows that incidence rates of lung cancer are increasing among younger women in the United States and other countries, according to study findings published in the Journal of the National Cancer Institute.
“In a number of studies, there have been indications that, at the same levels of smoking, women may be more susceptible to lung cancer than men,” first author Ting-Yuan “David” Cheng, Ph.D., assistant professor of oncology with the Roswell Park Cancer Prevention and Control team and assistant professor at the University of Florida, said in an interview with CURE. “Also, in patients with lung cancer who never smoked in their lifetime, the proportion of women is higher than men. We, therefore, hypothesized that steroid hormones, which differ between women and men, can be a factor influencing the etiology of lung cancer.”
To examine the association between smoking status, gender and the expression of different hormone receptors, the research team from Roswell Park Comprehensive Cancer Center in Buffalo, New York, collected tumor samples from 813 patients (450 women and 363 men). The researchers determined that the expression of estrogen receptor beta (ER-beta), a hormone receptor that is known to inhibit tumor growth, was lower in women than in men. They also found lower levels of this hormone in postmenopausal women and those who had never used hormone therapy.
“This suggests that circulating estrogen, which is reduced due to menopause and elevated due to hormone therapy, may play a role in modifying ER-beta levels,” he said. This study did not directly measure circulating estrogen, so a prospective study would need to confirm this finding, Cheng noted.
Hormone receptors may also be influenced by cigarette smoking, concluded the researchers. In the tumors of smokers, there were higher levels of the estrogen receptor alpha — this promotes tumor growth — than in people who had never smoked. Individuals, however, who smoked had lower expression of progesterone receptors. According to the researchers, this contributes to a poorer prognosis because progesterone can inhibit the growth of cancer cells.
“We observed that hormone receptor levels in lung tumor tissue were associated with survival in patients with lung cancer,” Cheng said. “Thus, hormones may play a role in influencing survival, and future research may build upon this. But the most important message is not to smoke. In research that we are conducting at Roswell Park, we have seen that among smokers with any type of cancer, their risk of dying is lower if they quit smoking, even if they only quit shortly after they are diagnosed.”
As next steps, the research team plans to explore genetic and nongenetic factors, such as hormone use, diet, and second-hand smoke, that can influence the hormone receptors. Additionally, they want to examine the hormone hypothesis in Asian populations.
“In our lung cancer study, there was a relatively high proportion of Asians who never smoked,” he said. “In Asian populations, the smoking rate among women is very low in general, but they have high lung cancer incidence, and the reasons are not clear.”
Cheng encouraged clinicians to advise patients, both men and women, to quit smoking and donate their unused surgical samples — parts of samples may remain after the doctor uses what they need for medical tests.
“Surgical samples have been a crucial part of research in cancer etiology and outcomes,” Cheng said. “Science can only go forward with the involvement of patients and communities.”