Key Point:

The incidence of lung cancer in women has risen markedly. Women have a higher risk of lung cancer than men do but survive longer once they have the disease.

NEW YORK CITY—Lung cancer is one of the leading causes of death worldwide. Although the incidence of lung cancer in men has dropped sharply in the last two decades, no comparable decrease has been seen in women. In fact, between 1930 and 1997, the rate of death from lung cancer in women increased 600%; lung cancer incidence rates have leveled off since then but have not declined.

Even worse, one quarter of adult women in the United States continue to smoke, and most of them started in their teenage years. Thus, lung cancer has been described as a “contemporary epidemic” in American women.[1] According to experts in the field, women appear to have a higher risk of developing lung cancer than men. However, once women have lung cancer, they survive longer than men with the disease.

WOMEN AT RISK

In comparison with men, women may be more predisposed to carcinogen-induced genetic mutations of the p53 gene. In addition, studies have identified more smoking-related DNA adducts in female lung cancer patients. The formation of DNA adducts depends on the balance between two processes: the rates at which carcinogens in tobacco smoke are oxidized and the rates at which reactive products are detoxified. In one study that reported higher numbers of DNA adducts in female lung cancer patients, the women had smoked for a shorter time than the men had and thus had lower carcinogen exposure.

Estrogen may also be a contributing factor. Expression of the hydrocarbon-activating CYPA1A1 gene is higher in female smokers than in male smokers.

The findings that β-estradiol causes proliferation in non–small cell lung cancer and that antiestrogens block the spread of cancer further suggest that estrogen signaling affects the biology of the lung. Women also have a lower DNA repair capacity than men do, and genetic mutations are more common in female smokers with non–small cell lung cancer than in their male counterparts.

According to Mark G. Kris, MD, Chief of Thoracic Oncology Services at Memorial Sloan-Kettering Cancer Center in New York City, “the genetic changes [affect] how the body handles cigarette smoke and the by-products of cigarette smoke. So, from a behavioral standpoint, stopping smoking is the way to negate these kinds of genetic changes and any kind of predisposition to either accelerate the effect of carcinogens or break down carcinogens.”

Although women are more likely to develop lung cancer, they survive longer than do men with the disease. This increased survival is not wholly accounted for by longer life expectancy or differences in factors affecting prognosis. “In general, no matter what cancer therapy you administer (chemotherapy, radiation, or surgery), women tend to do a little bit better. The newer drugs that block growth factor signaling are also more likely to benefit women,” Dr. Kris observed.

SMOKING

The increasing number of lung cancer cases in women is the result of a rise in smoking among women that began several decades ago. Following the first Surgeon General’s report on the health effects of smoking (released in 1964), smoking rates among men dropped sharply but decreased much more slowly among women; it was not until the early 1980s that women began giving up smoking at rates comparable to men’s. The large number of women who continued smoking in the 1960s and 1970s are now at risk for lung cancer. “That [is] a big cohort of people,” stressed Dr. Kris, “and because of that, we’re going to have more and more cases of lung cancer now.”

Although the fact that people are paying today for smoking they did decades ago is hardly new, Dr. Kris is not discouraged. In fact, he made two points about smoking: First, he said, “quitting at any stage, even when you have lung cancer, means that you’re going to live longer.” Second, “quitting at any point when you don’t have lung cancer lowers your risk of getting lung cancer—but it never goes back to zero,” he warned.

However, stopping smoking doesn’t solve the current problem, Dr. Kris pointed out. “We have tens of millions of women at risk for lung cancer because they smoked, and this epidemic is going to continue.” Even if everybody stopped smoking today, lung cancer incidence would still increase, he said, because of smoking that took place in the 1960s and the 1970s. “We need to focus societal efforts on doing something about lung cancer. There are 70,000 women with this disease. That’s not a tiny number, and lung cancer is fatal in the vast majority.”

—Gale Jurasek

Reference
1. Patel JD, Bach PB, Kris MG. Lung cancer in US women: a contemporary epidemic. JAMA. 2004;291:1763-1768.

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