Cancer Knows No Borders | The Scientist Magazine®

Cancer Knows No Borders | The Scientist Magazine®

Cancer Knows No Borders

Unafraid to tackle cancer disparities across races, Olufunmilayo “Funmi” Olopade has demonstrated that genomics research can make a big impact on public health.

By Megan Scudellari | August 1, 2013

THE UNIVERSITY OF CHICAGO MEDICINE COMPREHENSIVE CANCER CENTERIn November 1982, a military officer practicing on the soccer field outside the Nigerian Navy Hospital in Lagos, Nigeria, collapsed and died. Olufunmilayo “Funmi” Olopade, a young, newly minted doctor, was working inside when the man was brought in to the emergency room. “We couldn’t understand why he died,” says Olopade. “That really shocked me, and made me realize that I needed to do more to be able to understand and help people.”
Three months earlier, Olopade had visited her brother, a graduate student at Stanford University, and while in the United States, she flew to Chicago where she interviewed with and was offered a job at Cook County Hospital. At the time, she wasn’t sure she was ready to commit to a medical residency in the U.S. But the day the soldier died, Olopade called Cook County and asked if the position was still available. It was, and 2 months later, she was on a plane to Chicago.

“I think we can democratize how we prevent and treat cancer, so people on the periphery can take advantage of the research going on in the center.”

Olopade quickly rose in the ranks at Cook County, becoming Chief Resident in 1986, then going on to a postdoctoral fellowship in hematology and oncology at the University of Chicago with geneticist Janet Rowley. Today, 26 years later, Olopade is still at the university, where she’s built a career bridging research and medicine, races and borders.
In the early 1990s, Olopade opened one of the country’s first clinics for genetic testing of tumors. She has also pioneered the exploration of population differences in tumor biology, finding, for example, that women of African descent who contract breast cancer overwhelmingly have aggressive tumors characterized by BRCA mutations—tumors that do not respond to the traditional first-line hormone therapy used in the West. Today, Olopade is dedicated to using genomics, big data, and common sense to improve global health disparities.
Here, this physician-scientist mulls over what it’s like to be a MacArthur “Genius,” the physics obsession that led her into the arms of her husband, and how fears of genetic discrimination hinder scientific progress.

Olopade On the Move

Paging Dr. Olopade. Born in Nigeria in 1957 to a pastor and a homemaker, Olopade was the fifth of six children. “My father really wanted to have scientists and doctors in the family. My siblings before me were in engineering and science—none of them chose to be in medicine—so I was his second-to-last hope. However, at that time, I was fascinated by physics. I didn’t care much for biology, but in Nigeria the option available to me was to be a doctor. I didn’t have any theoretical-physicist role models. So I passed a qualifying exam and went to medical school.”

Fateful visit. Olopade spent a rigorous 6 years at the University of Ibadan, where she showed an aptitude for biochemistry and for experimentation. “I was drawn to pathophysiology, and I wanted to be a cardiologist, because it was applied physics plus physiology.” In 1981, the first of two summers that Olopade visited her older brother at Stanford, “he couldn’t say enough about some of the tools and resources available to do his work. Silicon Valley was booming; it was the place to be in the early 1980s. I visited the medical schools at UCSF and Stanford. That’s when I got exposed to American medicine and the opportunities that were here.” Olopade returned to Nigeria, passed the American medical boards, and “the rest is history,” she says with a laugh.

Chance of snow. Well, almost history. The following summer, when Olopade went back to the U.S. and was offered a job at Cook County Hospital in Chicago, she delayed taking it until the death of the young sailor spurred her into action. “I came to Chicago in January. It was quite shocking because I had no idea the temperature was going to be that different from when I had visited in September. As my plane landed, people were talking about ‘flurries.’ I had no idea what that meant.”

Solid start. Olopade completed an internship and residency in internal medicine in 1986. At the beginning of her training in hematology/oncology, the program director, Harvey Golomb, encouraged Olopade to try a stint doing research, specifically in a genetics lab, which he predicted would be a hot field. After reading a paper by renowned geneticist Janet Rowley describing chromosomal changes in cancer, Olopade applied for a fellowship in Rowley’s lab at the University of Chicago. “I was fortunate to get into her lab and learn molecular biology. It was the best of times. Rowley advised me that it didn’t matter what I studied, but that I learn the skills.” At the time, geneticists had made many discoveries concerning blood cancer, but little was known about genetic abnormalities in solid tumors. “I learned to do chromosome mapping, what we then called ‘chromosome walking,’ and chose to map chromosome 9—a region that had shown deletions in leukemias and lymphomas and now was showing up in some solid tumors.” Olopade reasoned that if there was a tumor suppressor gene on that chromosome, the gene would be important in multiple cancer types. Indeed, she subsequently identified and characterized a new tumor suppressor gene on chromosome 9.

Assessing risk. In 1991, Olopade opened her own lab at Chicago and continued to work on tumor suppressor genes, gradually shifting to the study of genetic predisposition to breast cancer. But while happily keeping busy in the lab, Olopade began to feel a widening gulf between her genetics work in the lab and her clinical care of patients. “It was really wonderful to be able to map and clone genes, but as I worked with families, and saw the suffering that they went through and the worry about whether they or their relatives would die from breast cancer like their mother had, I was very compelled. I wanted to figure out a way to begin to do genetic testing in the clinic. All of my medical training had always emphasized that prevention is better than cure, and while we were making major discoveries in genetics, it wasn’t really getting translated into prevention.”
In 1992, Olopade founded the Cancer Risk Clinic at the university to perform testing for cancer-susceptibility genes in concerned and high-risk individuals. “At the time, it was unheard of. We had a huge debate between geneticists and oncologists about whether this was a good thing to do or not.” In 1996, Olopade wrote a frank editorial in the New England Journal of Medicine declaring that it was time to begin using genetic testing in earnest for cancer risk assessment and personalized cancer therapies. She chastised the medical community because while wealthy, informed women were seeking out genetic testing from commercial laboratories, economically disadvantaged or uninformed women at high risk were not being tested due to limited access to genetic testing. “I was getting frustrated with how long it was taking us to take advantage of these genetic advances.”

Olopade Observes

Confronting the race question. Both at Cook County Hospital and at the University of Chicago School of Medicine, Olopade regularly saw African American patients with familial breast cancer, and she began to wonder if there was a link between breast cancer genetics and the African diaspora. “People at County Hospital were not different from patients in Nigeria, in their attitudes and the way they presented with illness. So I was really curious about whether that was something peculiar to people of the African diaspora—whether it was poverty, or an underlying genetic factor we had not paid attention to. The literature was filled with disparities about how black people did poorly in every aspect of medicine. Social scientists would say that was because they had no access to medicine, but I thought maybe it was how early life events could impact a person, such as how poor nutrition early in life can make you disadvantaged forever.” In 2005, Olopade proposed that not just genetic constitution but societal factors, such as toxin exposure and obesity, can vary by race or ethnicity and affect breast cancer incidence. “That work recognized the fact that there will be population differences in tumor biology based on what’s driving the tumor,” she says.

Triple threat. Then Olopade went back to Nigeria to examine genetic patterns of breast cancer in African women, as breast cancer is a particularly virulent disease for young women on the continent. In 2009, she published the groundbreaking finding that the majority of tumors in indigenous African women with breast cancer are triple-negative tumors, a particularly aggressive type of breast cancer that grows rapidly and does not respond to some of the low-cost treatments common in the region. “The conventional wisdom was that these poor women just delayed getting their cancer diagnosis, so when they showed up, the cancer was big. But now we know some of them are mutation carriers, and within 2 weeks [of onset] their cancer can get really big.” The finding suggested that mammogram screenings and current first-line treatments might not be the best way to control breast cancer in Africa. The study “brought awareness to the fact that the real thing causing health disparities was an overrepresentation of the most aggressive type of breast cancer among Africans and African Americans,” says Olopade.

Genetic guidance. Today, Olopade continues to study the population genetics of breast cancer. “We really need to understand these complex interactions to understand cancer and develop effective interventions,” she says. Last year, her team sequenced the BRCA1 and BRCA2 genes of 434 Nigerian breast cancer patients and found that the population has an exceptionally high frequency of mutations in both genes, suggesting that genetic counseling should be broadly disseminated in Nigeria and other understudied populations. Her team also recently identified unique BRCA mutations in African families that are significantly different from those seen in Caucasian populations, mutations that many BRCA genetic tests do not currently identify. “I truly believe that once you understand the genetic basis [of cancer in a population], then you can look at pathways to disrupt, and get better drugs and better prevention. If people were not so afraid of genetic discrimination, we could direct more genomics toward public health.”

Big ideas. “My main project now continues to be to understand how to use genomics to improve global health and global cancer research. I’m building a big database of cancer patients I can use to inform the treatment of any patient, no matter where they are in the world. I think we can democratize how we prevent and treat cancer, so people on the periphery can take advantage of the research going on in the center. With health information tools, we can actually do that.”

Olopade Opines

Language barrier. “When we started our work in Nigeria, there wasn’t even a word in the language for breast cancer. The only word they had was “ulcer,” which meant that the cancer was advanced and ulcerating. People were not making a diagnosis until it was too late. And it wasn’t that these women didn’t show up to the doctor. They went to a low-level health professional who misdiagnosed them and gave them antibiotics, because the professional didn’t even know it was cancer.” Olopade has since organized numerous conferences in the country to raise awareness about breast cancer. “Through advocacy and now the US government funding of medical schools there to reform curriculums, we’re having better success.

“If people were not so afraid of genetic discrimination, we could direct more genomics toward public health.”

Genius club. In 2005, Olopade was awarded a MacArthur Fellowship “Genius” Award, a prestigious recognition of “extraordinary originality” and a no-strings-attached stipend of $500,000. “It’s not a lot of money, but the MacArthur gives you the ability to attract more funding. It allowed me to really be a physician-scientist. Physician-scientists are a dying breed, and I was being compelled to choose one or the other.” With the additional funding and recognition, Olopade has been able to continue her work in both the clinic and the laboratory.

Physical attraction. Olopade and her husband met while both were in medical school in Nigeria. “He was playing cricket for the university team, and I played badminton and squash. I would go over and keep score for the cricket team, because I just loved the numbers and watching the trajectory of the cricket ball as they pitched. It was the most beautiful way I could enjoy physics and nature. And that’s how we met.”

Family hike. Olopade and her husband have three grown children, ages 24, 28, and 29. “Our family climbed Mount Kilimanjaro last year. Our daughter was reporting on a book about Africa and living in Kenya, and she asked if we could do Kilimanjaro as a family. We decided it should be all or none, so we all trained. I thought I was going to be the weak link, so I worked hard to make sure I wouldn’t get sick. We all made it to the top. It was amazing.”

Giving back. “You may find me during the week lecturing to Nobel laureates at the university, but on the weekend I’m at a black church at a community event speaking about health care. I also try to mentor kids from the community so we can get more individuals with African ancestry into STEM. Unless they can see a role model, they don’t think it’s possible. I tell them I couldn’t ever have dreamt that I’d be a professor of genetics at the University of Chicago, but if I can do it, anyone can do it.”