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ESTROGEN ACCELERATES PROGRESSION OF HEAD-NECK CANCER

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Estrogen might increase the movement of precancerous cells in the oral cavity, thereby promoting the progression of head and neck cancer, according to new research published in the January issue of Cancer Prevention Research.

"The finding is still from cultured cells in a dish, so we're far from the clinic, but the hope is that our research will lead to the development of new compounds that will block this progression," senior author Margie L. Clapper, PhD, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, told Medscape Medical News.

Exposure to tobacco smoke and use of alcohol are major risk factors for the development of head and neck cancer. More recently, infection with human papillomavirus has been linked to squamous cell cancer of the oropharynx.

However, a recent report indicates that 75% of individuals who develop primarily oral tongue squamous cell cancer are female, suggesting that estrogen contributes to the development of head and neck cancer.

In previous work, Dr. Clapper and her team from the Cancer Prevention and Control Program at Fox Chase reported that estrogen metabolism changes after tobacco smoke exposure in the lungs, suggesting that estrogen metabolism plays a role in the formation of lung and other cancers in the aerodigestive tract.

In the current study, the researchers, led by Ekaterina Shatalova, PhD, a postdoctoral fellow at the Fox Chase Cancer Center, examined the contribution of estrogen to the development of head and neck cancers.

They found that estrogen induces the expression of the cytochrome P450 1B1 (CYP 1B1) enzyme, which is responsible for breaking down toxins and metabolizing estrogen, but only in leukoplakia cells. In a surprise finding, the researchers discovered that estrogen did not induce the enzyme in cancer cells.

Specifically, exposure to estrogen increased levels of CYP 1B1 transcripts 2.3- to 3.6-fold, compared with control cells (P = .0004), in leukoplakia cells but not in head and neck squamous cell cancer cells.

When the CYP 1B1 enzyme was deleted, migration and proliferation of the precancerous leukoplakia cells were reduced by 57% and 45%, respectively.

The study also found that exposure of the precancerous cells to estrogen inhibited apoptosis by 26%, but supplementation with the antiestrogen fulvestrant restored estrogen-dependent apoptosis.

"In the future, we would like to find a natural or dietary agent to deplete the CYP 1B1 enzyme to see if we can prevent oral cancer at the precancerous stage," Dr. Shatalova said in a statement.

Dr. Clapper added that "our previous studies showed that the CYP 1B1 enzyme sits at the hub of changes that occur in the lungs after smoke exposure. CYP 1B1 could be a wonderful target in precancerous lesions of the head and neck because by attacking it, we might stop those lesions from progressing or from moving to a more advanced stage," she said. "In the lab, we reduced this protein genetically. But if we could find drugs or natural compounds that could reduce it, you can imagine that it might be a good treatment for cancerous lesions."

The results from this study might help researchers "understand factors that cause head and neck cancer, in addition to the traditional risk factors of tobacco and alcohol exposure," said Jennifer R. Grandis, MD, professor and director of the Head and Neck Cancer Program at the University of Pittsburgh School of Medicine in Pennsylvania, in a statement.

She added that because these results are limited to a single premalignant cell line, "further studies are needed to validate these findings in head and neck cancer in a human population."

Dr. Clapper and Dr. Shatalova have disclosed no relevant financial relationships. Dr. Grandis is an editorial board member for Cancer Prevention Research.

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