Shelley Tworoger

Shelley Tworoger, PhD, first discovered epidemiology through a chance conversation with her friend’s father. Now a member of the BWH Channing Division of Network Medicine and the faculty director of the BWH/Harvard Cohorts Biorepository, Tworoger works to identify biomarkers and risk factors of ovarian cancer through collaborative epidemiologic efforts, such as the Nurses’ Health Studies and the Ovarian Cancer Cohort Consortium.

BWH Clinical & Research News recently asked Tworoger about her ongoing research and many roles at BWH.

What does your research involve?

ST: My main scientific focus is to understand the origins of ovarian cancer and how we can prevent this disease. Ovarian cancer is the fifth most common cause of cancer death in U.S. women, even though it is a relatively rare cancer. Each year, 22,000 to 24,000 women are diagnosed, but they are generally diagnosed at a late stage when the disease is no longer treatable. Current screening modalities don’t reduce mortality, which I think lends itself to trying to understand what the risk factors are so we can try to improve prevention. My team is looking at a wide variety of these factors, including psychosocial stress. We’ve found that women with a diagnosis of depression or depressive symptoms were at a 30 percent higher risk of ovarian cancer. If confirmed in other large-scale human studies, this could really open up some new opportunities for identifying high risk women. We are also interested in looking at markers of inflammation and which aspects of this exposure are most important in ovarian cancer.

Ovarian cancer is not a single disease, so we are working to understand tumor heterogeneity as well. Even in large, long-term epidemiologic studies like the Nurses‍’ Health Studies where we collected data from 238,000 women, we don’t have enough statistical power to really start looking at the rarer subtypes. I received a grant from the Department of Defense to develop the Ovarian Cancer Cohort Consortium, which includes 25 prospective cohort studies from around the world. We are working to integrate questionnaire, biomarker, genetic and tissue based data into epidemiologic research to better understand how ovarian cancer risk factors differ by type of tumor.

Tell us more about your role in the Nurses’ Health Studies.

ST: I’m also the faculty director of the BWH/Harvard Cohorts Biorepository, which houses 3.5 million biologic specimens from six cohort studies. These include the Nurses’ Health Study I and II as well as the Physicians’ Health Study, the Health Professionals Follow-Up Study and the Growing Up Today Study, which is the children of the women in the second Nurses’ Health Study. A large part of my effort is designed toward improving the integration of biomarker research into epidemiologic studies, so we often pilot new technologies like ‘omic platforms.

We collected blood samples in the Nurses’ Health Studies at two different points in time. In addition, every two years, the women in the study get questionnaires about their health. If their medical records show they’ve been diagnosed with a disease like ovarian cancer, we can pull their blood sample from before the diagnosis and compare the biomarker levels with a woman who did not get the disease.

We’re also quite heavily involved in collecting other sample types beside blood. I recently did a collection in a subset of women of fasting blood, first morning urine samples, timed saliva samples, hair and toenails. I’m most interested in using this dataset to better understand how we can use biomarkers to measure chronic stress. Looking at whether stress influences risk of ovarian cancer has made me realize how difficult it is to capture stress exposure well.

Take us through your career path. How did you get interested in your field?

ST: I went to undergraduate and graduate school at the University of Washington in Seattle. I started out as a biochemistry major and then I applied for combined medical school and masters in public health programs because I was really interested in doing research. When I applied to medical schools, I was asked at every single interview why I didn’t just go to graduate school. So I thought, why not go to grad school – but I didn’t really know what to do because I had never heard of epidemiology before and I knew I didn’t want to do basic science. One of my friends said that I should talk to his dad, since he did research in human populations with a lot of statistics. I love statistics and math, so I said I would. His dad introduced me to epidemiology and I started doing research in the field. The confluence of working with people and dealing with data on a large scale was something that was really exciting to me. I wish that epidemiology was more well-known. I stayed on for an extra year in undergrad and did research in epidemiology at the Fred Hutchinson Cancer Research Center.

For my thesis, I worked with Scott Davis, PhD, a radiation epidemiologist, looking at the link between electromagnetic field exposures and sleep patterns. I also worked with Anne McTiernan, MD, PhD, studying how physical activity influenced biomarkers related to cancer.

Tell us about your experience at BWH.

ST: After graduate school, I was offered a job here working with Sue Hankinson, ScD, MPH, who was the director of the biorepository at the time. I had done a lot of work in biomarkers using biological samples in my graduate work, so the resources here were really exciting. Sue turned out to be an amazing mentor. She worked to integrate me into the daily life of the cohorts. She guided me when I became the biorepository director, which gave me the opportunity to interact with a lot of investigators and be exposed to all of the different ongoing research. Sue was my teacher in learning how to manage people and finances. She has a passion for helping junior faculty to succeed.

I wasn’t expecting to stay here as long as I have, but I really love the environment here. Everybody who works on the Nurses’ Health Studies has an investment in making these studies the best that they can be, and I think it fosters a different kind of collaborative environment across disciplines. For example, I’ve started collaborating with Frank Hu, MPH, PhD, who studies diabetes at the Harvard School of Public Health. You wouldn’t think somebody who studies ovarian cancer and someone who studies diabetes would have an intersection, but we do have some similar interests in certain areas. One of the things that I’ve found about the overall environment that is supported here is this idea that everybody’s scientific contribution is valuable and that everybody brings something different to the table. I really enjoy that aspect of my job here.

What are your long term goals with your work?

ST: My goal is that women don’t get ovarian cancer. The overriding goals of my research are to find ways to prevent ovarian cancer and to help identify women who are at high risk for ovarian cancer.

We do know how to prevent ovarian cancer in one sense: we can remove a woman’s ovaries and that reduces her ovarian cancer risk by up to 90 percent. The problem is that having your ovaries removed is harmful in other ways. There have been a number of studies that show that women who have their ovaries removed have an increased risk for cardiac events. Even in post-menopause, when ovaries aren’t that active, they’re still altering the hormonal environment in such a way that influences health.

We can’t just tell all women once they’re postmenopausal to go get their ovaries removed because we know that’s not the healthy choice. However, if we could identify women who are at really high risk of getting ovarian cancer, then the surgery may be beneficial for them on the whole. Right now, even with the risk factors that we do know, we are not yet very good at predicting which specific women are at high risk of disease. We need to identify new risk factors to help us identify those high-risk women who could benefit from more specific risk-reducing interventions.