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Signs of a Gender Gap

SPECIAL TO THE TIMES

There won’t be a dry eye in the house if Michele Reed gets to walk down the aisle in April and promise to love her new husband “till death do us part.” Less than a year ago, doctors told the 28-year-old Albuquerque secretary she had terminal lung cancer. She may not survive long enough for her wedding.

A light smoker, Reed never imagined that, at her age, backaches and neck pains could be the first signs of lung cancer. Neither did her doctors. By the time they ruled out stress, allergies and asthma, a tumor in her lung had grown to 4 inches wide and the cancer had spread to her bones.

“I seriously thought it was stress-related,” Reed said recently, after letting out a long, deep cough. “I would get this fluttering feeling in my chest. I didn’t know what it was. Now I do.”

Lung cancer is deadly for both sexes, but it is now killing more women than ever. That’s no surprise. The surge in female smoking that began in the 1930s started to ebb in the 1960s but continues to take its toll. What is surprising is that young women like Reed are dying from the disease.

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Scientists have suspected a lung cancer gender gap since 1995, when a prominent cancer journal reported that women smokers are nearly twice as likely as men to develop the disease.

The debate has been ongoing since, said Curtis Harris, the head of the National Cancer Institutes’ Laboratory of Human Carcinogenesis. “There are a number of studies showing that women have an increased risk of developing lung cancer if they are smokers,” he said. “But there are also papers that don’t show a difference. So it’s an unresolved issue.”

Now scientists are finding evidence that the gender gap is real. Female smokers appear to develop the disease earlier. They don’t seem to need to smoke as much as men to get ill. And nonsmoking women are more likely than nonsmoking men to develop the disease.

The interaction of cell biology, genetics and tobacco smoke may be the reason the disease seems to play itself out differently in men and women.

For years, lung cancer was a man’s disease. Men put down their pipes and cigars when cigarettes became fashionable around the turn of the century. And because society considered cigarette smoking unladylike until the 1930s, men started getting lung cancers first.

But by the time the U.S. surgeon general’s landmark report on smoking and cancer came out in 1964, cigarettes had begun to take a toll on women too. With that report came the “war on cancer,” and people began giving up smoking. At the same time, cigarette makers, who once targeted women by promoting their product as a way to lose weight, went for a liberation link with campaigns such as “You’ve come a long way, baby . . .”

The lung (and bronchus) cancer rate for men has declined from a peak of 75 deaths per 100,000 in 1990 to 68 deaths per 100,000 in 1996, according to age-adjusted data from the National Cancer Institute. The death rate for women has not declined. Although the sharp increases of the 1970s and ‘80s have slowed, the rate has grown from 13 per 100,000 women in 1973 to 34 per 100,000 in 1996.

Survival Rate Has Barely Improved

In general, cancer is not the death sentence it was in the 1960s. With early detection and better treatment, people now survive many once-fatal cancers. Lung cancer, however, is usually not one of them. From 1975 to 1990, the average survival rate for all cancers except lung cancer--that is, the percentage of cancer patients alive five years after diagnosis--rose from 56% to 67%. During that same period, the lung cancer survival rate hardly budged, moving from 13.4% to 13.9%.

This bleak disparity stems in part from the lack of a screening test for lung cancer similar to mammography for breast cancer or colonoscopy for colon cancer. Doctors usually detect the disease only after people develop symptoms. By then, it is almost always too late. Lung cancer kills about 160,000 people each year in the U.S.--more than breast, colon and prostate cancer combined. Lung cancer is also different from other cancers in that it is almost completely preventable. Between 85% and 90% of all lung cancer patients are current or former smokers. Yet, even as cigarette smoking becomes unacceptable in many once-welcoming settings--such as airplanes, break rooms and restaurants--about 25% of the national population still smokes.

That rate has essentially held steady for adults over the last decade. Smoking rates are even higher for teenagers and actually went up during the mid-1990s, peaking at 35% in 1997, according to the federal Centers for Disease Control and Prevention. The rate is leveling off and may even be declining for male students but remains virtually unchanged for females.

Most smokers start in their teens, but the cancers don’t usually kick in for about 40 years.

For some reason, lung cancer hit hard and early for Michele Reed, who said she smoked about three cigarettes a day for 10 years. An active, petite Arizona native who once spent weekends playing softball and exploring the desert in her four-wheeler, Reed had planned to quit smoking early enough to cut her risk of getting cancer. Even when she learned of her diagnosis, Reed assumed she had a good shot at surviving.

“You see stuff in the paper and you see the billboards [about smoking and cancer], but I didn’t realize that it was so hard to treat,” she said. “I knew people who had had cancer and had made it through. Medicine is so advanced. I just sort of took for granted that they can take care of anything.”

Reed has undergone two rounds of chemotherapy--treatment that doctors hope will shrink her lung tumors and make her more comfortable, but that will not cure her.

Rosi Slater’s prognosis is more positive. She had even less reason to suspect she had lung cancer, but a little more than a year ago, while nursing her 3-week-old baby, the Montana horsewoman developed a high fever and went to the emergency room. Doctors there X-rayed her chest looking for pneumonia but found a tumor in her lung instead.

“You just think that’s not possible,” said Slater, who had surgery and is expected to survive. “I’m not a smoker, I had my house tested [for cancer-causing radon gas]. I am the least likely 36-year-old on the planet to have lung cancer.”

Proof of Gender Gap Remains Elusive

Despite stories like these, population studies comparing large groups of male and female smokers have yet to definitively confirm the lung cancer gender gap theory.

Those studies can be easily confounded by factors researchers may fail to properly account for, such as secondhand smoke. (Some studies have found that nonsmoking women who live with smokers have a 20% higher risk of lung cancer than women who live in smoke-free homes.)

“Men and women have different occupations,” says John Wienke, director of the Laboratory for Molecular Epidemiology at UC San Francisco. “Then you have the possibility that they smoke differently. I think the molecular approach is going to be the way that we’ll really see if there is a difference.”

Working with researchers at Harvard University, Wienke was part of a team that found female lung cancer patients were more likely than men to carry a cancer-linked genetic mutation called K-Ras. Women with lung cancer are also more likely to have a deficiency in the body’s ability to repair damaged cells, according to research out of the M.D. Anderson Cancer Center at the University of Texas.

Another group of researchers at the National Cancer Institute found that nonsmoking women exposed to secondhand smoke are much more likely to develop lung cancer if they have a defect in a gene that helps detoxify tobacco smoke.

Cell biologist Jill Siegfried began working in this area a few years ago after she noticed that more and more of the lung tumor samples she was collecting came from women. The University of Pittsburgh researcher ran genetic tests on her tissue samples and found a piece of the puzzle that may explain some cancers in nonsmoking women.

Women are more likely than men to carry an active form of a gene that promotes abnormal lung cell growth that can lead to cancer. Men, Siegfried’s team found, need to smoke to activate the gene; women don’t. She found something else as well: The female hormone estrogen seems to fuel the growth of lung tumors in the same way it fuels breast cancer.

Just how close those pieces are to forming a whole picture remains a subject of debate. An upcoming U.S. surgeon general’s report on women and tobacco is expected to cast the issue of female susceptibility to lung cancer as an open question. Gender could simply be masking another risk factor, such as diet or a tendency to puff harder on the “light” cigarettes women favor.

Finally, many questions regarding gender and lung cancer remain unanswered. For example, women seem more likely to develop a type of cancer called adenocarcinoma, while in the past, squamous cell tumors made up the vast majority of lung cancer cases. There doesn’t seem to be a difference in survival rates, but researchers say that adenocarcinoma may be easier to detect because it is less likely to occur deep in the lung.

As far as Dr. Fred Grannis is concerned, he has all the evidence of a lung cancer gender gap he needs in the women who walk through his office door.

The head of thoracic surgery at City of Hope National Medical Center in Duarte, Grannis said the surge in the number of nonsmoking females he treats has been impossible to ignore or explain.

“We take very careful smoking histories, and a lot of these women do not have high exposures to environmental tobacco smoke,” he said. Scientists would call such evidence anecdotal--reports of a trend that has yet to be confirmed through controlled experiments.

“I think it’s way beyond anecdotal,” said Grannis, who has been treating lung cancer patients for more than 25 years. “What it is due to is the big question.”


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