As doctors have substantially brought down the rate of lung cancer in men over the past three decades, they face a stubborn riddle: Why does it continue to grow among women?

A new study offers an intriguing possibility that the answer may involve estrogen, the Wall Street Journal reported in its Tuesday edition.

Lung cancer is the leading cancer killer of both women and men. And overall, it still kills more men than women: About 71,000 deaths are projected in women and 86,000 in men in 2010.

That's a much higher casualty rate than the No. 2 killer, breast cancer, with about 40,000 deaths expected, according to the American Cancer Society.

Experts don't agree on whether women are naturally at greater risk for lung cancer or more vulnerable to the effects of tobacco smoke than men. Still, there are striking gender differences in cancer rates. For instance, women who have never smoked are far more likely than men who have never smoked to get lung cancer, according to data from the National Cancer Institute.

The diagnostic trajectory among women is concerning. Researchers are trying to understand why it is rising and what can be done to change it.

The hormone estrogen is a possible culprit. Certain forms of estrogen are known to help create genetic mutations in cells and contribute to tumor formation in the breast. Recently, researchers found out that lung cells in both women and men also make estrogen, raising the possibility that the hormone contributes to lung-cancer development.

Margie Clapper and her colleagues at Fox Chase Cancer Center, a major research center in Philadelphia, set out to examine what would happen to the lung cells of female animals that were exposed to tobacco smoke. They wanted to identify early genetic changes in the cells — before tumors formed — that could be targeted in the future.

The goal is that one day these early genetic changes could be disrupted, preventing lung cancer from developing in the first place, said Dr. Clapper, co-leader of the cancer prevention and control program.

The findings, published last week in the journal Cancer Prevention Research, "reinforce the role that estrogen is clearly a player and we need to look at it more closely," Dr. Clapper said.

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