Medical researchers are faced with solving a difficult puzzle. Why is the prevalence of lung cancer in men decreasing at the same time it is increasing in women?

Lung cancer in U.S. women is a contemporary epidemic that only recently has started leveling off. Since the mid-1970s, the incidence of lung cancer in women has increase six-fold, becoming one of this country’s major health problems.

The human and financial burden of lung cancer is hard to comprehend. Currently, U.S. women have the highest lung cancer rates in the world. Last year alone, lung cancer killed enough U.S. women to equal or surpass the entire population of Muncie, Indiana, and killed more than breast, ovarian and uterine cancers combined. Every year, approximately $9.6 billion is spent in the U.S. treating this disease.This scene is repeated in other top economic countries, and is expected to take its toll on emerging economic nations in the next few decades.

But why is this happening? The short answer is nobody knows for sure and some of the “causes” are still controversial, but there are some pretty impressive clues that have been uncovered.

The incidence for women we are seeing now is a result of the rise in women's smoking from decades ago, says Michael Thun, a researcher and former head of the surveillance and epidemiology at the American Cancer Society. "Women as a group started smoking later than men and are slower to quit, and smoking is known to be the biggest contributor to lung cancer," he said.

Cigarette smoking in men and women is thought to cause up to 90 percent of all lung cancers in the U.S. This is a major concern as epidemiological data suggest that women may be more susceptible than men to develop lung cancer.

Smoking explains part of the trend, but it falls short in making clear why there has been an increase of lung cancer in never smokers, like Dana Reeve, the wife of Superman actor Christopher Reeve, who died of the disease in 2006, at the age of 44.

Research conducted by Neal Freedman of the National Cancer Institute and published in The Lancet Oncology July 2008 edition, found that women who have never smoked seem to be at higher risk of developing lung cancer than men who have never smoked. Other studies suggest one-in-five lung cancers are seen in never smokers. The majority of these cases are diagnosed in young women under age 40.

While still controversial, research has found some evidence that estrogen production may play a part in this puzzle. As in breast cancer, estrogen can serve as a tumor promoter, some studies suggest. Many lung cancer tumors have been found to have estrogen receptors on them in both men and women. The current hypothesis is since women produce more estrogen than men, they are more likely to have a reaction with the estrogen receptor in the tumors.

Beyond hormones, a laundry list of other factors may be putting women who have never smoked or former smokers at risk for lung cancer, including exposure to the human papilloma virus (HPV), hormone replacement therapy, as well as certain biomarkers that are more prevalent in women than men. Add environmental factors, such as exposure to secondhand smoke, asbestos, air pollution, high levels of arsenic in drinking water and radon gas in homes, and occupational exposure to dry cleaning chemicals and those used in nail salons and unraveling the lung cancer puzzle gets increasing complicated in the modern world.

While researchers don’t all agree on why women are increasingly being diagnosed with lung cancer, they do agree that lung cancer is woefully underfunded, in part because fewer lung cancer advocates exist when compared to other cancers. One reason is only about one in 10 patients live long enough to advocate on behalf of the disease.

Generally speaking, the news around lung cancer seems grim, but improvements in treatment have made leaps and more is known about this disease than just a few years ago, putting recovery in the grasp of more lung cancer patients.

Lynette Summerill is an award-winning writer who lives in Scottsdale, Arizona. In addition to writing about cancer-related issues, she writes a blog, Nonsmoking Nation, which follows global tobacco news and events.