Scientists have found why lung cancer rates are increasing in women, particularly in non-smoking women.
Researchers at Fox Chase Cancer Center, led by Dr. Margie Clapper, worked in a mouse model of smoking-induced lung cancer.
They found that smoke triggers rapid changes in gene expression in the lungs of female mice, including increasing expression of a network of genes involved in estrogen metabolism.
Based on these data, the team hypothesizes that estrogen metabolism may contribute to lung cancer in non-smoking women as well.
Following smoke exposure for 3, 8, or 20 weeks, Dr. Sibele Meireles, an assistant member in the Clapper Lab, found that 10 genes were differentially expressed in the lungs of smoke-exposed female mice as compared with control animals.
The gene most affected by smoke was cytochrome P450 1b1 (Cyp1b1), which is responsible for breaking down toxins and is a key enzyme for estrogen metabolism.
Additionally, when the team looked at networks of genes, they saw that genes involved in estrogen metabolism were altered within the lungs of animals exposed to smoke as compared to controls.
"We found a link between hormones and lung cancer through Cyp1b1 when we weren't looking for it -very exciting. Previous work has suggested that estrogen may play a role in lung cancer, but no one has shown that smoke can actually accelerate the metabolism of estrogen within the lungs; the suggestion from our data," said Clapper.
The investigators hypothesize that estrogen plays a role in the formation and progression of lung cancers, similar to the role it plays in some breast cancers.
The idea is consistent with previous studies indicating that women with lung cancer who take hormone replacement therapy have a poorer prognosis than women who do not, regardless of their smoking history.
Additionally the observation that estrogen can be detected within the lungs and that its metabolism is unregulated in the lungs of smoke-exposed female mice may provide new insight into why lung cancer is rising so quickly in women, including non-smoking women world wide, according to Clapper.
The investigators decided to look at gene expression changes after short-term smoke exposure in hopes of finding ways to intervene in or reverse the process.
"If we can identify the earliest events that happen within the lungs when you begin to smoke, we might be able to use therapeutics to block them as well as lung cancer," said Clapper.
The study was published in the TK-ISSUE of Cancer Prevention Research.