Goal of next massive decades-long cancer study: reduce cancer to a nuisance

Before the first cancer prevention studies run by the American Cancer Society between 1952 to 1955, and again between 1959 and 1972, Americans had no idea that smoking causes cancer. Before the Cancer Prevention Study II, which started in 1982, physicians and patients didn't fully understand the link between nutrition, obesity and cancer.

The University of Alabama at Birmingham just became the largest enrolling center in the next study in this series, Cancer Prevention Study-3, or CPS-3, with a record 1,209 people signed up to participate at UAB. Nationally, the study will follow the health of 300,000 people for decades in hopes of making the next great leap in the understanding of what causes cancer.

Specifically, the study will track the lifestyle, environments, diet and genetics of people not previously diagnosed with cancer in hopes of understanding what causes or prevents cancer for each person in the coming decades. The ultimate goal is to turn cancer from a major killer into a manageable, chronic disease (a nuisance) or stop it before it starts.

We thought to ask Edward Partridge, M.D., director of the UAB Comprehensive Cancer Center, about the science behind massive, long-term studies like CPS-3, and about why they reveal clues about diseases that other studies miss. 

Show notes for the podcast:

1:06 Population-based studies like this are especially important because they enroll large numbers of people who are well at the beginning of study. Researchers can they see who gets sick over time, and go back to indetify which factors were associated most closely with disease. Sadly, a good many of the people in the study will develop cancer in the coming years, Dr. Patridge said. Was it a certain kind of food, or a certain certain of a gene that created risk? This is a different type of approach than studies that look at whether a drug will work in people who are already sick.

3:14 Massive, decades-long studies reveal patterns where other studies cannot because of the detailed tracking of so people and so many factors for so long. In addition, what the study designers decide to track in each patient is based on many studies in recent years that offered new clues about what to track. Participants take an original survey, which includes trying to recall what their lifestyle was like in their youth, and then repeat the survey every two years. The first of the CPS-3 study results might come out within a year, with more results will then continuing to come out for decades.

4:38 Importantly, this is the first large cancer prevention study that is taking a blood sample from every participant. That will enable researchers to study genetic factors, and their combination of withf other diseases, medications taken. diet, etc., over time.  The research team will also be able to look at epigenetics, the small chemical changes that turn genes on or off in reaction to the environment. In the future, this may enable the field to recognize future cancer risk from a blood sample taken from a perfectly healthy person and in time to intervene.

6:09  The CPS study before the current one, CPS II, led to a publication in 2001 that found obesity to be a major contributor to cancer. Today, some make the arugment that obesity has overtaken tabacco as the major cause of cancer.  In 1970, four percent of children between the ages of six and eleven were obese. Today, that number is 20 percent, a five-fold increase. Children who are obese are much more likely to become obese adults, and public health experts fear that a wave of obesity-related cancer is on its way. CPS-3 will include the largest percentage of obese people of any cancer prevention study so far, and the obesity-cancer link will be closely tracked. 

7:41 Other burning questions in cancer research that CPS-3 will help to answer are, for instance, what is the molecular basis of the increase in cancer risk related to obesity. Researchers will also be looking at what the drop in smoking has meant in terms of reduced risk. Researchers are also keen to study for the first time many of the pharmacuetical drugs taken now taken by so many Americans for large portions of their lives. For instance, what are the long-term effects of a drug like metformin, taken for Type 2 diabetes, on cancer risk?  It may actually reduce cancer risk and the study may explain why. 

9:23 Among the most exciting things about the study is the combination of taking blood samples and the fact that researchers have now mapped the human genome, the complete set of genetic material. That will enable researchers to see which deviations from normal genes are associated with cancer. Dr. Partridge said that he believes this study, and related efforts worldwide, will have eliminated cancer as a major public health threat half-way through the study, say by the year 2050.  By then, the field will detect and eliminate cancers before they become a health threat, or will be turning them into a chronic, manageable conditions, the way drug cocktials have enabled many AIDS patients to live normal lifespans. 

12:19  In a sign of the challenges involved in curing cancer, our society has not yet fully made use of the knowledge and data collected by cancer prevention studies that finished up decades ago, said Dr. Partridge. We all know that smoking causes cancer, and yet 22 percent of Americans still smoke, and even more Alabama. We know that colorectal cancer and mammography saves lives, and yet 40 percent of people with insurance don't opt for these tests. The new study will reveal many insights as well, but making the cultural changes needed to realize their value will be a larger task.

13:45 The fact that so many enrolled locally here in Birmingham says great things about the community, Dr. Partridge said.  He found it particularly gratifying that so many UAB employees enrolled. UAB is a major employer here, and to see nurses, staff, physicians and researchers, many of whom conduct research for a living, becoming participants in research.

14:54 Local enrollment in CPS-3 is closed, but folks can still visit the CPS-3 website to see what the 
nearest enrolling center is. The study will finish up enrolling nationally by December 2013.

Food fungus worsens African AIDS epidemic

I keep coming across factors that, while not directly related to the nature of the human immunodeficiency virus (HIV), are nonetheless driving the African AIDS epidemic.

Take the recent news about a study from the School of Public Health, which found that a type of fungus coating much of the stored corn, rice and nuts in many African and Asian countries may be weakening immune systems and encouraging HIV infection.

Kept in sacks piled in warehouses, food stores in countries near the equator are often contaminated by Aspergillus flavus and A. parasiticus, fungi that produce a toxic substance called aflatoxin.

About 4.5 billion people worldwide are exposed to aflatoxin at unsafe levels, and chronic exposure has been linked to liver damage and related cancers.

Work by Pauline Jolly, Ph.D., professor in the Department of Epidemiology within the UAB School of Public Health, argues that aflatoxin exposure may be taking an even greater toll in areas where millions are infected with HIV. The research team divided 314 HIV-positive people from Kamasi, Ghana, into four groups based on their level of aflatoxin exposure.  The team found that those in the highest exposure group were 2.6 times more likely to have a high HIV viral load than those in the lowest exposure group. Higher viral load translates into higher rates of HIV transmission. For information, please see our news release and related coverage by the New York Times.

Along the lines of non-viral factors worsening the AIDS epidemic was another study published this past August, also from the School of Public Health. Janet Turan, Ph.D., associate professor in the Department of Health Care Organization and Policy, and her team found that the fear of being labeled HIV-positive was strong enough to keep mothers from Kenya from having their babies in health-care facilities. Communities there have come to see clinics and skilled care as mostly for HIV-positive women, and HIV often is linked to promiscuity in the eyes of a woman's family.

In Nyanza, Kenya, a region where one in five pregnant women is HIV-positive, skilled care during pregnancy and birth increases the likelihood that those infected will receive antiretroviral drugs that prevent the passing of HIV from mother to child.

It just seems like Africa can’t get a break.

More troubling yet, the search for solutions to the epidemic's many contributors is not accelerating in the age of research budget cuts. The grants that paid for Jolly's research into the aflatoxin and HIV have ended, leaving her unable to pay for a full data analysis of the consequences of combination exposure on sets of immune cells. She does not know where her next round of funding will come from.

“A fungal contribution to HIV transmission will only be proved once and for all by larger randomized studies for which there now is no funding," Jolly said. "The scientific and world-health communities need to decide soon whether or not this question is worth answering.”

The hard work of making cities smart and green

By 2050, 90 percent of Americans will live in cities that consume most of the nation's energy and generate most of its greenhouse gases. Whether sprawling cities devolve into ecological disasters or slowly transform into smart, sustainable economic growth engines will depend partly on the next generation of engineers and the technologies they invent.

To face the challenges posed by megalopolises, experts say Americans need to do more than just upgrade the current, rusting infrastructure. In a perfect world, future cities would boast advanced public transportation systems, renewable energy resources,"complete streets" and green roofs. Birmingham aspires to become such a place, with a new kind of UAB campus at its heart. Solar-powered electric vehicles would traverse its avenues passing facilities cooled in part by the breeze instead of fossil-fuel-burning air conditioning.

As a step toward this futuristic vision, Fouad H. Fouad, chair of the UAB Department of Civil, Construction and Environmental Engineering – and director of the UAB Sustainable Smart Cites Research Center – recently convened the second annual Sustainable Smart Cities Symposium. We thought the meeting made for a good occasion to ask him about related research frontiers. It's an exciting time, but there is still a long way to go, with progress slowed by economic hard times and the slow pace of technological development. When will U.S.-made solar panels, for instance, be cheap enough to compete with fossil-fuel-generated electricity?

For any city re-imagining itself as sustainable, the effort must start with investment in smart, green infrastructure – power, transportation and buildings, according to Dr. Fouad.

Power
On the frontiers of alternative power generation, Alabama Power is currently testing solar panels at 50 locations across the state. Unfortunately, Alabama is not windy enough for massive wind power projects using current technologies, but engineers continue to experiment with the viability of rooftop units.

Research is underway in UAB Mechanical Engineering on the next generation of solar cells, some of the work done in combination with Alabama Power, said Dr. Fouad. UAB Energy Management’s dream is to carpet the roofs of UAB’s buildings with solar panels but presently, projects would take 30 years to generate enough savings to pay for themselves – in part due to the relatively low utility rates in Alabama.

Transportation

Smart, green transportation systems are a major ingredient in future-looking cities, with related efforts seeking to create new street plans that favor non-motorized traffic, take advantage of biofuels and launch electric vehicle fleets.

In terms of city planning research, Fouad said his team is doing many studies on congestion management.  Dynamic signaling systems may make it possible to better route traffic to lessen traffic jams. Thanks to a grant from the U.S. Department of Transportation, UAB recently joined the National Center for Transportation Performance and Management to conduct multi-disciplinary research on sustainable transportation infrastructure, economic competitiveness and safety.

Other concepts under investigation by UAB civil engineers include the "complete street," where city streets are designed to accommodate foot and bike traffic as much as motorized traffic. A UAB demonstration project is planned for 10th Avenue in combination with The Regional Planning Commission of Greater Birmingham, said Dr. Fouad.

Under the heading of green fuels and vehicle fleets, the planning commission's partnering initiatives include Alabama Partners for Clean Air and the Alabama Clean Fuels Coalition. Recent related news includes the announcement by the City of Trussville that it's expanding its fleet of compressed natural gas vehicles and opening a CNG fueling station. Compressed natural gas is a fossil fuel substitute for gasoline that is more environmentally sound. CNG may also be mixed with biogas, produced from landfills or waste water, which doesn't increase the concentration of carbon in the atmosphere.

UAB Civil Engineering has a project underway in conjunction with the Jefferson County Transit Authority and the U.S. Federal Transit Administration to design and construct a prototype for a hydrogen fuel cell powered bus, which they hope could be the workhorse of new green public transportation fleets in Birmingham. The first vehicles should on the road later this summer, said Fouad. Such vehicles make electricity to power the car using hydrogen, and they give off nothing more than water vapor from the tailpipe. On the consumer front, Honda and Toyota are getting closer to producing hydrogen-powered cars that could be sold to consumers, but they will be costly to start.

Alabama Power is also experimenting with fleets powered by alternative energy sources, and to date has more than 100 electric vehicles and 50 charging installations. The UAB Department of Energy Management has purchased two electric cars that are charged entirely by solar panels, which offer them the chance to evaluate a grid-free transportation technology with no carbon footprint.

Buildings and bridges
The UAB Department of Materials Science & Engineering has great research strength in the design of green composite materials for building, Dr. Fouad said. Often such materials are made from recycled materials and are lightweight, stronger and less expensive to use. His smart cities center will be participating in the Alabama Composites Conference starting on June 18 in Birmingham.

UAB Civil Engineering is also designing materials for use in the building of next-generation, critical infrastructures like the highways and bridges. Dr. Fouad is an expert, for instance, in autoclave-aerated concrete, which is filled with air bubbles such that it requires one-fifth of the weight of classical concrete to create a material that is much stronger. Composed of 80 percent air, it promises to deliver huge savings to the industry while creating an air-bubble barrier in building materials that insulates the building against energy loss. The barrier of air within the concrete acts as thermal installation, reducing heating/air conditioning costs.

UAB civil engineers are also looking at what's next for materials used to make bridges. Along with bridge materials research, projects underway are studying "bridge way in motion" sensors that send messages continually about the structural health of bridges to ensure timely maintenance, not to mention alerting authorities when trucks breaking weight limit laws cross bridges.

Also maturing are research efforts to develop green roof technology, where plants grown in soil beds on roofs conserve energy and improve air quality as plants turn carbon dioxide generated by cars into oxygen. Green roof test beds are currently in place atop the Hulsey Center, the Business and Engineering Complex, Campbell Hall and Hill University Center at UAB. They limit water runoff into the storm water drains, pumping it back through the irrigation system, which keeps polluted water from running into area creeks and the Black Warrior River. The presence of plants and surrounding soil controls water evaporation in a way that creates a cooling effect. Combined with the moist soil, this helps drop temperatures and has resulted in a 20 to 25 percent savings in power bills.

Both the vegetative and white reflective roofs are perhaps 80 degrees cooler in the mid-day summertime than standard black roofs, which can literally be used to fry eggs. The Alabama Department of Environmental Management is interested in promoting the adoption of vegetative roofs across the state.  

Impact on health
One of the most exciting projects underway is a partnership between Civil Engineering and the UAB School of Medicine's Division of Preventive Medicine. Called the "Go-ing Forward Project," it seeks to determine how the condition of the "built environment" in a city - the streets, lighting, housing, sidewalks, etc., - impacts the health of city dwellers. UAB researchers are going door to door surveying residents to determine how various aspects of the built environment are impacting their lives. The project's emphasis is looking at how transportation options, urban design, infrastructure decay, safety and security, and housing conditions affect obesity. More than one third of the American population is obese.

From the layout of streets to the options available for exercise, to the quality of air and water and to the condition and upkeep of residences, the built environment exerts silent but significant influence on the likelihood that people will be obese. Of all the engineering factors correlated with negative health outcomes, housing conditions are the most closely tied to health impacts. The presence of mold and its impact on asthma, poor indoor air quality in private homes and certain pollutants (e.g. estrogen-related compounds) in drinking water are all hypothesized to contribute to obesity risk.

Looking for partners
It was no accident that Richard Michos - global vice president, Smarter Cities, from IBM, was invited to speak at Fouad's recent UAB Smart Sustainable Cities symposium. UAB and the City of Birmingham hope to partner with IBM, perhaps through its Smarter Cities Challenge. This competitive IBM grant program is in the process of awarding $50 million worth of technology to 100 cities around the globe. These grants are designed to address the wide range of financial and infrastructure challenges facing cities today. Fouad met with Michos and Mayor Bell while Michos was in Birmingham, with their discussion covering the potential for IBM doing an assessment of the city's greatest sustainability needs, which is expected to yield a report and contribute to an action plan.

Speaking of partnerships, the City of Birmingham and UAB took a step toward smarter, healthier and more sustainable development with the Feb. 27, 2013, signing of a memorandum of understanding to partner on projects such as energy efficiency and city planning that accounts for a more “livable” city. Pilot projects expected out of the partnership include research into new recycling systems and lighting systems downtown that use less energy, perhaps in partnership with IBM.

UAB is also discussing the idea of creating a master's program in Sustainable Smart Cities, which would move forward with contribution from the deans and leadership of several schools across UAB.

For those interested in more information, other good sources include the UAB sustainabiltiy page and My Green Birmingham.

Image post 3: dangerous clumps of fungus

While most posts from The Mix feature a science story, we have also begun sharing images coming out of UAB research. Below is a brief description of what we are looking at and how related work may help to diagnose and treat fungal infections.

Here is a scanning electron microscope image of the fungus called Aspergillus. It's in the process of germinating, or emerging from round spores (at the center) to begin growing. The fungus has sprouted long, branching filaments called hyphae.

Most people breathe in Aspergillus spores daily without incident, but those with lung diseases or weakened immune systems can contract Aspergillosis, symptoms of which range from allergic reactions to severe lung infections. The fungus is a major player in some forms of allergic asthma, as clumps of hard-to-remove hyphae build up in the lungs.

According to the CDC, fungal infections pose an increasing threat to public health because of the growing number of people with weakened immune systems, including AIDS, cancer and transplant patients. In addition, treatment-resistant fungal infections have emerged as a growing problem in hospitals. Global warming may be contributing to an increase in infections, as fungi thrive in warm, moist conditions. Please see the CDC fungal page for more.

Current treatments are largely incapable of reducing morbidity and mortality in Aspergillosis, said John Kearney, Ph.D., professor in the Department of Microbiology within the UAB School of Medicine. He and his team are developing a new kind of vaccine that could provide protection against invasive Aspergillosis. Bacteria elicit a stronger human immune response than fungi but contain some of the same proteins (e.g. chitin). Based on these common building blocks, it may be possible to develop a vaccine where bacterial protein vaccine ingredients are used to activate immune cells that also target a fungus and remove it from the body.

This image was made by Dr. Jeffrey Sides from the Kearney laboratory at UAB using an instrument made available by the UAB School of Engineering.