Are Women More Susceptible to Lung Cancer Than Men?

Although lung cancer was once thought of as a "man's disease," over the past several decades, women have been catching up. Today, lung cancer is the deadliest cancer among women -- killing more women than breast cancer, uterine cancer and ovarian cancer combined. The American Cancer Society estimates that in 2017, 105,510 women will have been diagnosed with lung cancer and 71,280 women will have died of the disease. Compare those figures to men's statistics -- 116,990 new cases diagnosed and 84,590 men dying of the disease in 2017.

The ACS reports that "the lung cancer rate has been dropping among men over the past few decades, but only for about the last decade in women." The America Lung Association reports that although more men are diagnosed with lung cancer each year, more women live with the disease, and the rate of incidence in women has only started to level off recently. "The rate of new lung cancer cases (incidence) over the past 39 years has dropped 32 percent for men while it has risen 94 percent for women. In 1975, rates were low for women but rising for both men and women. In 1984, the rate of new cases for men peaked (102.1 per 100,000) and then began declining. The rate of new cases for women increased further, did not peak until 1998 (52.9 per 100,000) and has now started to decline."

[See: 7 Things You Didn't Know About Lung Cancer.]

So what's driving these rates and why is there a sex difference in lung cancer? "There's multiple theories, but no definitive answer," says Dr. Karen Reckamp, associate professor of medicine and medical director of thoracic oncology at City of Hope Comprehensive Cancer Center in Duarte, California. One theory is that hormones could be a contributing factor. Some forms of cancer, including cancers of the breast and prostate, rely on hormones to grow, and some studies have shown that certain forms of lung cancer also feed on estrogen.

Additionally, some studies have shown a potential link between hormone replacement therapy and a worse outcome for women with lung cancer. Although there is some conflicting data out there, and it's unclear whether HRT increases a woman's risk of developing lung cancer in the first place, some evidence suggests that if she has lung cancer, HRT can lead to "a more aggressive cancer," and a higher likelihood of dying of the disease, Reckamp says.

Environmental and genetic aspects also contribute. "We don't understand that fully, but there are definitely genetics involved with it, and we're doing some work in trying to understand the genetics of lung cancer," Reckamp says. The hope is that down the road, this research will lead to better screening tests, similar to how breast cancer patients are often tested for genetic mutations on the BRCA gene, which have been conclusively linked to an increased risk of developing breast cancer. This may lead to screening of lower-risk individuals and a cure for lung cancer, but "we're not there yet," Reckamp says.

In investigating the genetic mutations that can lead to lung cancer in both smokers and never-smokers, researchers at Memorial Sloan Kettering Cancer Center found that women seem to be more susceptible to genetic mutations that result in lung cancer. Dr. Marc Ladanyi, a lung cancer researcher and chief of molecular diagnostics at MSKCC, says this 2012 study didn't set out looking for differences between men and women but found them anyway. "We were looking at lung cancers that have KRAS mutations, which is the most common mutation in lung cancers." Building on other research that showed cigarette smoking causes specific changes to the DNA sequence of lung cells, Ladanyi and his team noted a difference in the type of KRAS mutations among smokers versus nonsmokers. Smokers are more likely to have a KRAS G12C mutation, whereas other KRAS mutations were found more often in never-smokers, Ladanyi says. (The ACS reports that up to 20 percent of lung cancer deaths each year -- about 30,000 people -- occur in people who never smoked.)

[See: What Not to Say to Someone With Lung Cancer.]

Because the study was so large -- including more than 3,000 patients -- Ladanyi says his team was able to "identify subtle differences" among patients that led to a discernment that women may well be at higher risk for developing lung cancer than men. "Along the way, we compared men and women with how frequently they had this KRAS G12C mutation if they were smokers, and it was more common in women. The women were younger when they were diagnosed and had a shorter smoking history, so it really suggested that women were at risk from smoking for this KRAS mutation triggering a lung cancer based on a shorter smoking history than men. So we think that women are more susceptible based on this KRAS mutation," Ladanyi says. The age difference Ladanyi mentions is 65 for women versus 69 in men, which may not seem that big in absolute terms, but was "very significant" statistically speaking, he says.

Although this study didn't assess the mechanism by which these genetic mutations seem to happen more frequently in women, cigarette-for-cigarette, women appear to be at higher risk of developing lung cancer than men because of a "heightened susceptibility to tobacco carcinogens," the study reports.

As science gets closer to pinpointing exactly which genetic mutations can lead to lung cancer, that could lead to better screening tests. Even so, Reckamp says it's unlikely that all women would be routinely screened for lung cancer such as they generally are for breast cancer because of challenges associated with screening for lung cancer. Currently, the best screening tool available for lung cancer is a low-dose CT scan, but in lower risk individuals, it often leads to false positives and unnecessary biopsies that are invasive and can cause complications. This is because the lungs are deep inside the body and hard to access surgically. "With breast cancer, you can do a biopsy with minimal invasion," Reckamp says. "But when you have lung cancer or a nodule of the lung and you have to biopsy it, there are potential complications associated that are higher risk than a breast biopsy."

Taken all together, this means regular screening for lung cancer is generally reserved for high-risk individuals -- those who have a 30-pack-year or higher smoking history. (The National Cancer Institute calculates a pack-year "by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, 1 pack year is equal to smoking 1 pack per day for 1 year, or 2 packs per day for half a year, and so on.") For people with this sort of smoking history, low-dose CT screening has been shown to be effective in finding lung cancers earlier.

[See: 7 Innovations in Cancer Therapy.]

Reckamp says that women who are concerned about their risk of developing lung cancer can lower that risk by simply not smoking. Recommendations "No. 1, 2 and 3 are don't smoke, and if you do smoke, stop smoking. Even though there are stories of people who have never smoked and young people getting lung cancer, still by far, the highest risk is people who smoked or are currently smoking. Stopping smoking and not using tobacco products is incredibly important," she says.

Ladanyi agrees. "Even without a mechanism worked out about why women seem more susceptible, I think it's yet another reason for women to avoid or stop smoking," he says.

Elaine K. Howley is a freelance Health reporter at U.S. News. An award-winning writer specializing in health, fitness, sports and history, her work has appeared in numerous print and online publications, including AARP.org, espnW, SWIMMER magazine and Atlas Obscura. She's also a world-record holding marathon swimmer with a passion for animals and beer. Contact her via her website: elainekhowley.com.