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Stalking the Beast: Cancer

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The young woman in the wheelchair wears a white headscarf and robe. Her left hand trembles as she speaks to the doctor in whispers. Something is wrong, she tells him. Something in her brain. She finds it difficult to focus on his face--one of her eyes keeps wandering.

It's a late morning in June, and outside, the Egyptian sun is blazing. Inside the cancer center, a dozen people sit on rows of plastic chairs not far from the woman, waiting.

In a dark room just off the hallway, a patient lies face-down on a gurvey, waiting to undergo radiation. A black X marks the spot on her right hip where technicians will point their wizardry. Upstairs in the pediatrics ward, children with huge eyes sit on beds as IV tubes feed them drugs.

Twice each week, Stacey Fedewa and her fellow American students catch a Cairo train and travel 60 miles north, through rice paddies and cotton fields, to this building in the city of Tanta. There, they pore through data as part of a $1.2 million training program funded by the National Cancer Institute in Bethesda, Maryland.

The students work on laptops in a room outside the medical director’s office, not far from the clinics and treatment rooms. Sometimes patients wander into the room in tears and ask if the director could look at a worrisome lump or feel a swollen thyroid gland. That’s when Fedewa looks up from her computer and remembers: this is the human face of the disease she has traveled 6,000 miles to try to prevent.

Cancer has been around for millennia—Egyptian mummies show evidence of tumors—but although scientists have identified the pathways by which some cancers work, many elude understanding.

“It’s a complex disease. It demands a global approach, with multiple collaborators,” says Amr Soliman, an associate professor of epidemiology at the University of Michigan School of Public Health. Soliman directs the NCI–funded SPH training program, Cancer Epidemiology Education in Special Populations, which sent Fedewa and four of her classmates to Egypt last summer and placed a half-dozen more SPH students in cancer clinics and registries around the world.

Globally, cancer kills six million human beings a year. Because it usually takes decades to wreak its cellular havoc, it is a greater threat to people in the developed world, where life expectancy is long. But increasingly it’s a worldwide plague.

The disease strikes different populations differently. Israelis suffer high rates of colon cancer; Moroccan women are prone to cervical cancer; liver cancer is especially prevalent in China. Breast cancer hits African-American women both earlier and more aggressively than it does white American women, and the rates of inflammatory breast cancer are ten times higher in North Africa than they are anywhere else in the world.

In its very diversity, however, scientists see new hope of decoding cancer’s secrets. Rare cancers, in particular, demand a collaborative approach, because the cases are too few and too scattered for concentrated study. But Soliman believes a multidisciplinary, global assault on the disease is the key to tackling all cancers. Without diversity—geographical, ethnic, behavioral, environmental—“you can’t see patterns and similarities.” Without a combination of disciplines—microbiology, histopathology, virology, computer science, nanotechnology, health education-—you can’t track how the disease evolves.

Gone are the days when cancer researchers worked in isolation, Soliman says.

His students call him “the guru of cancer epidemiology.” A former secretary calls Soliman the “now man” and indeed, he has the energy of a kid at a birthday party and the gleeful, high-pitched laugh to match. The Egyptian-born Soliman is bent on solving at least some of cancer’s riddles in his lifetime. Besides his SPH appointment, he’s a member of the UM Comprehensive Cancer Center, and he’s collaborating on three international studies to identify genetic traits, environmental exposures, interpopulation differences, and other factors to explain why certain cancers attack some but not others.

These are the kind of questions that perplex and fascinate Soliman and his collaborators, several of whom gathered in Ann Arbor last spring for a wide-ranging discussion of the disease. One debate centered around why bladder cancer is the leading cause of cancer among Egyptian men. Schistosomiasis, a parasitic disease that breeds in and around the Nile River, is a probable factor, but is it the only one? What about exposure to arsenic?

Arsenic is prevalent in Bangladesh and Taiwan, said Paolo Boffetta of the World Health Organization’s International Agency for Research on Cancer, which is funding one of Soliman’s studies —and those countries don’t show high rates of bladder cancer. In southern Spain, on the other hand, there’s little arsenic, but the incidence of bladder cancer is high. Perhaps it’s because people in southern Spain smoke black tobacco, Boffetta suggested.

Joe Harford, director of the NCI’s Division of International Affairs, which funded Soliman’s training grant, wondered if researchers should focus on exactly how people smoke. “Do they leave cigarettes in the ashtray while they talk in a cafe?”

“People do not change their genes,” Soliman points out. So by looking at behavioral influences and environmental exposures—in addition to genetic factors—he and his colleagues hope to deduce the causes of particular cancers and then to design prevention strategies. “Prevention is the beginning of the fight against cancer,” he says, “and prevention starts from epidemiology.”

Ideally their work will benefit both international and U.S. populations. “You can do work on original populations in Africa and then compare it to similar populations in the U.S.,” says Sofia Merajver, who directs the UM Comprehensive Cancer Center’s Breast and Ovarian Cancer Risk and Evaluation Program and is collaborating with Soliman on a study of inflammatory breast cancer, or IBC. With its substantial African- and Arab-American populations, Merajver adds, Michigan is an ideal place for launching cross-population studies.

She and Soliman and their colleagues know that success depends on their ability to analyze massive quantities of data from all over the globe, and that to get it they’ll need a small army of specially trained, passionate epidemiologists.

Enter Stacey Fedewa and students like her. Fedewa had never traveled to the developing world, but a long family history of cancer drove her to sign up for Soliman’s introductory course on cancer epidemiology.

It’s part of a new curriculum that provides required and elective courses, seminars, and special studies for the school’s new Cancer Epidemiology Education in Special Populations Program, which Soliman directs. Students in the program apply for summer field internships funded by the NCI training grant, and Fedewa was one of 11 to get one last year. She left for Egypt in May to spend the summer collecting data for a UM bladder-cancer study under the supervision of Soliman and his SPH colleagues Mark Wilson, professor of epidemiology, and Jerome Nriagu, professor of environmental health sciences.

In Cairo, Fedewa shared an apartment with several other SPH interns in the program. One of them was California native Kate Allen who, like Fedewa, grew up around cancer. When Allen was a kid, her mother was diagnosed with skin and then cervical cancer—both of which she survived—and as a result, the disease doesn’t frighten Allen. In fact, her mother’s experience taught Kate the importance of prevention. “My mother was always having moles removed,” she remembers.

The 26-year-old Allen spent her summer internship drafting, translating, and testing a questionnaire for North African women, which Soliman and Merajver would later use in their IBC study.

One of the most important things students on the program learn, Soliman says, is cultural sensitivity. How do you ask someone about body weight in a country where being thin is a sign of illness? How do you discuss cancer prevention in a village where people believe in the evil eye?

Soliman, who has lived in the U.S. since 1989, knows how tricky such encounters can be. He cut his epidemiological teeth on a huge study of diarrheal disease in Egypt in the 1980s, with findings that helped lower childhood mortality rates in that country from 250 deaths per 1,000 live births to 25 per 1,000. But he also spent eight years at the University of Texas M.D. Anderson Cancer Center in Houston. Equally at home in the developed and developing worlds, he says the training program “is not a lab experiment, where you have control over everything. You study people as they are.”

Soliman’s former M.D. Anderson colleague Bob Chamberlain, who chairs the external advising committee for the Michigan program and also directs the largest NCI–funded cancer-prevention education and teaching program, calls the summer internship “the real growth experience.”

Besides Egypt, the program’s 2007 interns traveled to Morocco, Tanzania, Turkey, Jordan, and India, as well as to California and several sites in Michigan, including an Indian reservation in the Upper Peninsula. They culled and analyzed data for international studies of liver, breast, bladder, pancreatic, cervical, and breast cancers. Soliman spent much of the summer dogging the students. On planes, in airports, maneuvering a rental car through Cairo’s clogged streets, in a half-empty cafe in Casablanca and a medical center in Dearborn, Michigan, he kept after them: How’s the questionnaire coming along? What does the data reveal? Have you set up an appointment with Dr. Ibrahim?

“If you want to work with me, you’ve got to be productive,” he says bluntly. “I’m not just nice. The part that will make us friends is productivity and work.” The students are expected to publish their findings, and here too Soliman goads them. His goal is to produce at least 10 specialists in international cancer epidemiology over the five-year period of the NCI grant. His long-range goal is to “motivate and encourage these young people to pursue international cancer epidemiology.”

But even students who don’t become specialists will benefit, says Chamberlain, “whether they work for a health department in Detroit or do world research. That’s one reason NCI thought it was so valuable.”

Unless trends change, cancer in the developing world is expected to represent 70 percent of global cancer cases by 2030, says NCI’s Harford. “As an institution with an international mandate, NCI’s challenge is not just to eliminate suffering and death due to cancer in the U.S., but to do so worldwide.” Because it’s designed to produce a new generation of epidemiologists able to conduct cancer research anywhere in the world, the Michigan training program is critical to that effort. “The mission to train both American and foreign nationals to battle cancer is one we take very seriously,” Harford says.

Soliman is already working to disseminate the program to other American universities. Meanwhile, for scientists like Merajver, the training grant and the data it’s yielding have been a godsend. Because she works on such a rare cancer, Merajver has often had to “scrape up dollars and cents” to fund her work on IBC. The grant changes that.

“People are waking up to the fact that people are the same everywhere, and that it is our moral and economic and scientific obligation to carry the bastion of research in the world,” Merajver says. “We must go where the diseases are to understand them. Often this means studying disease in societies that don’t have our wealth of resources. In that way, we all—Dr. Soliman and everyone—work not just for scientific understanding, but for peace.”

Inside the Tanta Cancer Registry, stacks of yellow and blue books hold data culled from 57 sites in Egypt’s Gharbia Province. The data reveal things like the rising incidence of liver cancer in the region, and the fact that childhood lymphomas are more common than leukemias.

It’s a good scientific base with which to start studies on the relationship of cancer to the environment, says Ibrahim Seifelden, who directs the Tanta Cancer Center. “You can put many hypotheses to study.”

Findings from the registry have helped Seifelden and his colleagues design early-detection programs for certain cancers, and the center’s clinics are now filled with well patients in addition to those seeking treatment. People increasingly show up before symptoms appear, drastically boosting their odds of survival.

The registry didn’t exist until 1999, and it’s the only one of its kind in Egypt. Hussein Khaled, dean of Egypt’s National Cancer Institute, is working to establish a nationwide cancer registry, but such undertakings depend on help from the developed world, he says. Students like Soliman’s can devote time and resources to tasks that their understaffed, underfunded Egyptian counterparts cannot.

Last summer, for instance, Fedewa and her fellow interns assessed the geographic distribution of bladder cancer in Ghar-bia Province and compiled population details for each of the region’s 316 villages and eight cities, including Tanta, so that officials at the Tanta Cancer Center could see the precise incidence and clustering of bladder cancer throughout the province. The students discovered a significant spike in one district. Fedewa says she may someday return to Egypt to understand why.

“Something’s there,” she says. “I just don’t know what it is.”

Mohammed Ramadan, who coordinates the Tanta registry, says the Michigan students “direct us to fine details that allow us to refine our work.”

On the other side of the African continent, pathologist Mehdi Karkouri of the University of Casablanca Cancer Center—one of several sites, including Egypt, where Kate Allen tested her breast-cancer questionnaire—says Michigan’s training program and the interns it sponsors bring “technical how-to-do” to his lab. “It is something like a locomotive, which scales up research in our department.”

In Dearborn, Michigan, at the medical center of the Arab Community Center for Economic and Social Services (ACCESS), UM researchers and students are comparing what they’ve learned abroad with data about Arab- American populations in the U.S. It’s another piece of the global cancer puzzle: translating overseas findings into education and prevention stra-tegies at home.

Farida Hatem, a Syrian-born Dearborn resident and a breast-cancer survivor, says she’s a “direct beneficiary” of the UM’s efforts to turn cancer from a bewildering scourge into a chronic disease, and she is grateful.

In a room outside the director’s office in an Egyptian cancer center, in a Moroccan laboratory, in a cancer ward in rural Tanzania, on an Indian reservation, epidemiologists from Michigan are at work. One finding at a time, they are pushing back the disease. And this, as Sofia Merajver puts it, “is how the circle closes.”

By Leslie Stainton

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