Friday, October 22, 2010

Genes influence how much people smoke and who gets lung cancer

Jerry Stitzel, University of Colorado, Boulder
The CHRNA gene is active in brain areas linked to addiction. In this image from a mouse brain, the bright white areas are the brain regions in which the gene is highly active.

Your DNA influences how much you smoke and whether you will develop lung cancer or chronic obstructive pulmonary disease (COPD), according to an international team of researchers led by Washington University School of Medicine in St. Louis.


The study is the first large-scale effort to match genetics with smoking, lung cancer and COPD combined. The investigators studied 38,000 smokers and found that two groups of gene variants on chromosome 15 influence risk for all three problems. Their findings appear in the journal Public Library of Science (PLoS) Genetics.

“We put together a consortium from around the world and analyzed DNA variants that we know cause biological changes in smokers,” says the study’s senior investigator Laura Jean Bierut, MD. “We were able to demonstrate that both of the variants affect the amount a person smokes. Then we showed that the same pattern of variants contributes to lung cancer and COPD.”

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Monday, October 18, 2010

At the heart of prevention


Photo by Bob Boston
Graham Colditz, MD, DrPH (left), goes over epidemiological research with Victoria Anwuri, project manager of the Siteman Cancer Center. “Graham Colditz is an exceptional leader,” says Larry J. Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine. “He has a clear vision for what it takes to build a world-class program and the keen ability to bring out the strengths in those he works with to accomplish that vision.”


By Caroline Arbanas
 
Growing up in Sydney, Australia, Graham Colditz, MD, DrPH, always knew he wanted to be a primary-care physician — just like his father.


But when he got to medical school, Colditz was struck by the kinds of patients he saw in the hospital. Too many were suffering from heart attacks or lung cancer — conditions linked to smoking. “It made me wonder: Couldn’t we do a better job at prevention?” he says.

That line of questioning changed the trajectory of Colditz’s career. Today, he is an internationally known leader in cancer prevention. Rather than treating patients after they get sick, his life’s work focuses on understanding the preventable causes of chronic disease, particularly among women, and translating that research into guidelines and policies aimed at promoting healthier lives through prevention.

After 23 years at Harvard University, Colditz joined the School of Medicine faculty in 2006 as the Niess-Gain Professor and associate director of Prevention and Control at the Siteman Cancer Center. His longtime associate at Harvard, Carol Leighton, joined Colditz, bringing her knowledge of research structures and implementation planning. Since his arrival, he has broadened the scope of prevention research, education and community outreach and markedly raised the profile of the university’s public health initiatives.

“Graham Colditz is an exceptional leader,” says Larry J. Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine. “He has a clear vision for what it takes to build a world-class program and the keen ability to bring out the strengths in those he works with to accomplish that vision.”

Colditz has recruited more than a dozen new faculty members whose research focuses on cancer’s link to physical activity, obesity and other lifestyle factors, and on public health strategies to help eliminate cancer disparities. He also has brought in more than $30 million in federal funding to expand the breadth and depth of cancer prevention research and programs.

Working with Edward F. Lawlor, PhD, dean of the George Warren Brown School of Social Work, Colditz was instrumental in establishing the university’s Institute for Public Health. The institute has expanded its interdisciplinary research and education programs to improve public health throughout the city, region and world.

Ahead of his time

After finishing medical school and an internal medicine residency at the University of Queensland in Brisbane, Colditz headed to Harvard University’s School of Public Health. He came with a dual interest in epidemiology and health policy.

As it turns out, Colditz was way ahead of his time. From the outset, Harvard epidemiologists advised him to steer clear of health policy.

“Clearly, their thinking was that epidemiology generates the truth and that policymakers could debate the research, but epidemiologists shouldn’t be involved in those discussions,” he says.

Colditz, however, wanted to bridge the divide. He wanted to apply the data, not just generate it. Colditz took courses in health economics and decision analysis and joined forces with health-care economists building a model that estimated the costs to society of smoking. Early in his career, he also was at the forefront of efforts to develop cancer prevention programs on the local, state and national levels, working with the city of Boston, the state of Massachusetts and the American Cancer Society.

Colditz earned a master’s degree in public health in 1982 and a doctorate in public health in 1986, also from Harvard.

For his dissertation, he worked on the landmark Nurses’ Health Study. This long-term study, initiated in 1976, has tracked the health of more than 238,000 nurses and is one of the largest investigations into the risk factors for chronic illnesses in women.

After finishing his doctorate, Colditz ran the day-to-day operations of the Nurses’ Health Study and, in 1996, became its principal investigator.

Through his efforts, the study was expanded to include data on fractures, diabetes, quality of life after breast cancer, tissue samples from premalignant and malignant lesions, and other health measures. Hundreds of studies since have been published based on data from the study. Among its major findings:

Smoking increases the risk of heart attacks and strokes in women.

Hormone replacement therapy increases the risk of breast cancer.

Even modest weight gain in adulthood increases a woman’s risk of diabetes.

Weight loss after menopause reduces risk for breast cancer.

“The Nurses’ Health Study is a massive undertaking,” Colditz says, “but it really gave us a incredible opportunity to look at how diet, physical activity and other lifestyle factors influence a woman’s risk of disease.”

New opportunity

Colditz’s son, Andrew Butler, PhD, began doctoral studies in psychology at Washington University in 2003, so Colditz knew of the school’s reputation and its academic rigor. Several years later, when former Harvard colleague Timothy J. Eberlein, MD, director of the Siteman Cancer Center, was looking to recruit someone to lead the Cancer Prevention and Control program, Colditz was intrigued.

Colditz was well aware of health disparities in the region. Missouri and Illinois both have cancer death rates higher than the national average; the problem is particularly worrisome in urban and rural areas with high poverty, where rates of smoking and obesity also are high. Some might look at those statistics as hopeless, but Colditz saw them as an opportunity and a challenge.

“We’ve got a phenomenal opportunity here to bring people together to change some of these disparities,” Colditz says.

Colditz and Aimee James, PhD, assistant professor of surgery, and other colleagues recently received additional National Institutes of Health funding for a major project to increase colorectal cancer screening among underserved and underinsured people in St. Louis and in Illinois.

Colditz also has spearheaded the development of the new master of population health sciences program for physicians and clinical trainees. He directs the one-year program, which launched this fall and is designed to give clinicians the research skills to evaluate the effectiveness of medications or clinical procedures in large populations.

“Graham has accomplished so much in such a short time,” Eberlein says. “Graham has a real gift for creating an environment where people want to work together. He’s a fantastic mentor, and everyone wants to work with him.”

In recent years, Colditz’s own research has focused on how diet and lifestyle during adolescence can influence cancer risk in later years. He has shown that regular exercise in girls as young as 12 can reduce their risk of breast cancer. In another study, he found that girls and young women who drink alcohol increase their risk of benign breast disease, which in itself raises their risk of breast cancer.

He also has initiated an effort to collect blood samples and health histories of the 25,000 women who get mammograms at the Joanne Knight Breast Health Center at Siteman. The information will be used as part of clinical studies to determine why certain women get breast cancer and why they respond differently to treatment.

“Washington University has enormous strength in basic science research and in understanding how disease develops,” Colditz says. “The challenge is to add ways to identify disease risk — both for individuals and within whole communities — and to change behavior to lower risk and improve people’s lives.”

Fast facts about Graham Colditz

Hometown: Sydney, Australia

Family: Wife, Pat Cox; son, Andrew Butler, PhD, 30, postdoctoral research associate at Duke University; daughter, Louisa Butler, 26, studying communication planning and information design at Carnegie Mellon University; daughter-in-law Anne Butler, 29, second-year epidemiology doctoral student at the University of North Carolina at Chapel Hill

Honors and awards: Member, Institute of Medicine; fellow, Australian Faculty of Public Health Medicine; Royal Australasian College of Physicians; Distinguished Alumni Award, Harvard School of Public Health

Valuable tool: Colditz and colleagues developed Your Disease Risk, an online tool to assess a person’s risk for cancer, heart disease, diabetes, stroke and osteoporosis.

Monday, October 4, 2010

Tradition of excellence

Kerry Kornfeld, MD, PhD (right), professor of developmental biology, and lab manager Luke Schneider observe C. elegans nematodes, the model organism Kornfeld uses to study cell pattern formation during development and aging. “(Kerry) is an outstanding developmental biologist and geneticist, a superb thinker and a wonderfully thoughtful person who was able to quickly forge connections between faculty and students in several departments, including molecular biology and pharmacology and genetics,” says Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and professor of medicine, of pathology and immunology and of developmental biology.


When Kerry Kornfeld, MD, PhD, says his life began at the School of Medicine, he means that literally.
 
“I was born at Barnes Hospital,” says Kornfeld, whose research laboratory is located a stone’s throw from the place of his birth.

As the youngest branch on a family tree with deep roots at the School of Medicine, Kornfeld, professor of developmental biology, is carrying on the family’s tradition of excellence in both research and service.

The first of Washington University’s elite cadre of faculty members known as “Dr. Kornfeld” was Kerry Kornfeld’s grandfather Max Kornfeld, the youngest member of the Washington University School of Dentistry’s Class of 1924. Max Kornfeld began teaching metallurgy and comparative dental anatomy at his alma mater in 1925.

The next Dr. Kornfeld at WUSTL was Max’s son Stuart, who completed a medical degree at the School of Medicine in 1962 and joined the faculty in 1966. Today, Stuart Kornfeld, MD, is the David C. and Betty Farrell Distinguished Professor of Medicine, co-director of the Physician Scientist Training Program at the School of Medicine and a world-renowned physician-scientist.

It was Stuart Kornfeld’s marriage to graduate student Rosalind Hauk during his medical training that led to Kerry Kornfeld’s aforementioned birth at Barnes Hospital.

“My mom (the late Rosalind Kornfeld, PhD) had my older sister and me while she was working on a doctorate in biochemistry,” says Kornfeld of his mother, who completed the doctorate in 1961 when Kerry still was an infant.

In 1966, Stuart and Rosalind Kornfeld joined the medical school faculty and began a professional collaboration that would lead to significant scientific discoveries.

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