Research Notes

Updated 10:00 AM July 6, 2004

Research Notes

Genetic risk factor for colon cancer identified

An international research team studying Israeli colon cancer patients has identified a new virulent genetic risk factor, a discovery that could lead to early screening methods to save the lives of people who have this genetic disposition for colon cancer.

The team—led by Dr. Stephen Gruber, who directs the U-M Health System (UMHS) Cancer Genetics Clinic, and Dr. Steven Lipkin of the University of California, Irvine—discovered a novel mutant gene that significantly increases the risk of colon cancer.

The researchers found that people with this genetic variant form of MLH1—a gene already linked with colon cancer—have a 40 percent lifetime risk of getting colon cancer, compared to a 6 percent risk for the general population. Study results appeared last month as an advance online publication on the Web site of Nature Genetics.

Colorectal, or colon, cancer is one of the most common forms of the disease in the United States, and rates in Israel are among the highest in the world. It is preventable through early detection.

During the past three years, the research team has been conducting a genetic epidemiological survey of colon cancer patients in northern Israel and found that more than 1 percent carried this previously unidentified variant gene, called MLH1 D132H.

Significantly, these patients were found to have no other risk factors, and they could not be identified with one particular ethnic, cultural or religious group.

"Because this genetic change is found in colon cancer cases from all major ethnic groups in Israel, it's likely that the genetic change also plays a role in colorectal cancer in other populations," says Laura Rozek, a post-doctoral research fellow at UMHS who led the study's analytic effort. "People with this genetic change are five times more likely to develop colorectal cancer than the general population."

Others from U-M who worked on the study included Joel Greenson and Eric Fearon of UMHS. The American Cancer Society, Ravitz Foundation and National Institutes of Health provided funding.
—Nicole Fawcett, UMHS Public Relations

Workers need to feel they're making a difference

When workers are aware that their work makes a difference to others—even in small ways—their job satisfaction and productivity rise, according to research recently presented at the annual American Psychological Society convention.

Most efforts to improve worker productivity hurt job satisfaction while efforts to boost worker morale tend to lessen productivity, but few factors have been shown to promote both, says Adam Grant, an organizational psychology doctoral student.

Grant thought researchers could find ways to make workers more productive and happier at the same time. He conducted several experiments and field studies to look at a variety of workers from firefighters to telemarketers. Grant found that feeling your work had a positive impact on others was important for both job satisfaction and productivity.

The study found 10 of 60 firefighters hoped they could fight more fires so they could have a greater impact on people. And among telemarketers, those who believed their work had a positive impact on others were more satisfied with their jobs and had more sales per hour.

"Most work makes a difference in someone's life in some way, or else the job wouldn't exist," Grant says. "We found that something as minor as showing people the client who benefited from the work made them care more. Just seeing that person, not even talking to him, could make them care more about what they were doing."'
—Joseph Serwach, News Service

High mastectomy rates due to breast cancer patients' choices

As surgeons develop ways to make breast cancer treatment less invasive and less disfiguring, mastectomy rates have remained surprisingly high, causing many researchers to suspect doctors are not giving their patients these options. But a new study shows it's the patients who are choosing the more aggressive surgery.

Researchers at the Comprehensive Cancer Center (CCC) and Wayne State University found that women with breast cancer who said they made their own treatment decisions were more likely to have a mastectomy than women who said their surgeon made the decision. Among women who had a mastectomy, fewer than a third received reconstructive surgery to create a new breast.

Results were presented last month at the annual meeting of the American Society of Clinical Oncology.

Breast-conserving surgery, called lumpectomy, is a less invasive option for women with breast cancer. The surgery involves removing only the tumor and a small margin of tissue around it, and cosmetic results can be almost unnoticeable. Meanwhile, advances in reconstructive surgery have allowed doctors to improve the cosmetic results of mastectomy, which removes the whole breast.

All women surveyed reported being most concerned about their cancer coming back and said that was the primary basis for their treatment decisions. Women who were most influenced by concerns about recurrence or the effects of radiation therapy, which is standard after lumpectomy, were more likely to have received mastectomy.

Dr. Steven Katz—associate professor of internal medicine at the Medical School and of health management policy at the School of Public Health (SPH), and a member of CCC—directed the study. Co-investigators were Nancy Janz, associate professor of health behavior and health education in SPH and a member of CCC, and Paula Lantz, a member of CCC and associate professor of health management and policy at SPH. Other authors from U-M were Angela Fagerlin, Barbara Salem, Indu Lakhani and Mahasin Mujahid, all from the Department of Internal Medicine. Funding came from the National Cancer Institute.
—Nicole Fawcett, UMHS Public Relations

Most of us are poor judges of our own abilities

If you believe you're a good driver or a lousy dancer, think again.

Most of us believe we can gauge accurately how our personal performance and abilities stack up against our peers, but research suggests that we are in fact poor judges of our own comparative talents.

Researchers from the Business School, Duke University and the University of Chicago report that people at all skill levels, including top achievers and poor performers, show similar degrees of inaccuracy and bias in making interpersonal comparisons.

These errors in judgment are tied to perceptions about the difficulty of an assigned task. When the task seems hard, top achievers underestimate their standing relative to their peers, resulting in less accurate predictions. When a task appears to be easy, poor performers overestimate their relative standing, making their predictions less accurate.

"Judgments of relative ability play an important role in decisions about engaging in competitive activities, purchasing goods and services, and undertaking challenging tasks," says Katherine Burson, assistant professor of marketing at the Business School.

"Overestimates of relative ability can lead to frustration, loss and even physical harm, as in the case of beginning skiers who attempt to ski advanced trails," Burson says. "On the other hand, there also are significant domains in life where relative ability may be underestimated, so people fail to participate when they would have succeeded."
—Bernie DeGroat, News Service

Quality of life affected long-term after treatment for prostate cancer

Four to eight years after men undergo treatment for prostate cancer, they continue to see changes—both positive and negative—in their quality of life because of that treatment, researchers at the U-M Health System (UMHS) and Harvard Medical School report.

While previous research has documented the effects of prostate cancer treatment on quality of life two years after it occurs, this is the first study to look at these issues beyond five years after treatment.

Researchers compared outcomes for men who had undergone surgery, external radiation and brachytherapy—a type of radiation in which seeds are implanted inside the prostate. Results of the study were presented in May at the American Urological Association annual meeting.

"Over the long term, some men who are treated for prostate cancer may continue to have varying degrees of urinary, sexual or bowel dysfunction when compared to men without prostate cancer. When we looked beyond two years of follow-up, we saw quality of life outcomes continue to change for men treated with either type of radiation—some for the better and some for the worse," says lead author Dr. David Miller, a fellow in urology at the Medical School.

Aging may have contributed to some of these changes, as the external radiation patients were older than those who had undergone surgery, he notes. For men who had surgery, quality of life tended to be stable, and their situation at two years was similar to their situation after more than six years.

Other authors from U-M were Rodney Dunn, UMHS research associate; Hector Pimentel, a Medical School student; Dr. James Montie, professor and chair of urology; Dr. Howard Sandler, professor of radiation oncology; Dr. P. William McLaughlin, professor of radiation oncology; and Dr. John Wei, assistant professor of urology.

Funding was from the National Institutes of Health and the Department of Urology.
—Nicole Fawcett, UMHS Public Relations

Why island populations are susceptible to exotic diseases

Researchers have shown that Darwin's finches on smaller islands in the Galapagos archipelago have weaker immune responses to disease and foreign pathogens—findings that could help explain why island populations worldwide are particularly susceptible to disease.

New research on finches helps scientists understand how island populations respond to invasive parasite species. (Photo courtesy Robert Rothman)

The paper was written by Johannes Foufopoulos, an assistant professor at the School of Natural Resources and Environment who specializes in disease ecology, and collaborators from Princeton University and the University of Upsalla. It investigates the relationship between immunological investment (how developed the body's immune system is), native parasite abundance and island size. The findings were published online June 8 in the Proceedings of the Royal Society of London.

The paper helps scientists understand how island populations respond to invasive parasite species. The introduction of exotic parasites and diseases through travel, commerce and domestic animals and the resulting destruction in native wildlife populations is a worldwide problem, Foufopoulos says, but it's even more serious for species that have evolved on islands.

The team found that finches on smaller islands with fewer parasites had a weaker immune response, and that when new parasites accidentally are introduced by humans to these islands, the birds are ill-prepared to resist infection.

In the Hawaiian islands, many native bird species have gone extinct after the introduction of avian malaria, Foufopoulos says. Galapagos authorities are realizing that the greatest danger to the islands' wildlife comes from exotic species, such as invasive pathogens, accidentally introduced by humans.
—Laura Bailey, News Service

Dementia often leads to nursing home admission

Nursing home admissions remain steady, even though Americans have more options in caring for elderly loved ones today than in the past and the medical community has new ways of treating Alzheimer's disease.

Those with dementia are at least twice as likely as those without it to be admitted to a nursing home, according to an article in the April/May/June issue of Alzheimer
Disease and Associated Disorders.

Jane Banaszak-Holl, associate professor of health management and policy at the School of Public Health, is the lead author of a study analyzing data from nearly 7,000 respondents who participated in the Institute for Social Research's (ISR) Health and Retirement Study between 1993 and 2000.

She says marked changes in nursing home alternatives—such as skilled home care and in improved treatments for Alzheimer's disease—have made previous studies seem outdated.

"To some surprise, our study results indicate that those with cognitive impairments remained at high risk of nursing home admission, despite the increasing availability of substitute services and advances in clinical treatment options," the journal article states.

Among the researchers findings: even modest improvements in physical function can cut the likelihood of entering a nursing home significantly, and dementia has a stronger effect on nursing home admission than most other chronic medical conditions.

Co-authors from U-M were Ken Langa, an assistant professor of internal medicine and faculty associate at ISR; Dr. A. Mark Fendrick, associate professor of internal medicine-general medicine and of health management and policy, and director of the Health Services Research Core Laboratory; Dr. Norman Foster, senior research scientist in the Institute of Gerontology (IoG) and professor of neurology in the Medical School; A. Regula Herzog, senior research scientist at IoG and at ISR's Survey Research Center, and adjunct professor in the Department of Psychology; and Mohammed Kabeto, research associate II at the Department of Internal Medicine.
—Colleen Newvine, News Service

When blood can't get to the brain, CT scan helps guide treatment

It's a no-brainer that the brain needs a constant supply of blood to keep it going. But some medical conditions—such as a stroke, a clogged artery or a brain tumor—can block or reduce that life-giving flow.

Newly published research shows that an innovative type of brain scan quickly tells doctors exactly where any of these problems lie and helps them decide how to restore blood flow. It can be done on computed tomography (CT) scanners found in many hospitals.

That's the conclusion of two papers published in the June issue of the journal Radiology by a team from the U-M Health System. The researchers detail the many potential uses of a technique called perfusion CT, including their own research results and data from a few other teams worldwide.

Members of the team, who have used perfusion CT clinically for several years, hope their new findings and their comprehensive review of the literature will help many other hospitals decide to adopt the life-saving technique.

"It's still a relatively new technique, but it could be adapted to any newer-generation CT scanner and be used to image acute and chronic cerebrovascular conditions," says Dr. Ellen Hoeffner, lead author of one of the papers and an assistant professor in the Department of Radiology in the Medical School. "It still isn't completely validated for use in some conditions, but more research will help."

Other authors were Dr. Gregory Thompson, an associate professor in the Department of Neurosurgery; Dr. Suresh Mukherji, director of the Division of Neuroradiology; radiologists Dr. Rajan Jain, Dr. Sachin Gujar, Dr. Guarang Shah, Dr. John Deveikis and Dr. Ruth Carlos; former neurosurgery fellow Dr. Mark Harrigan; and radiology administrative associate Ian Case. The study was funded internally.
—Kara Gavin, UMHS Public Relations

Homebuyers want view of woods, not large lawns

People prefer a view of the woods over a manicured lawn, a new study finds, suggesting a potentially huge untapped real estate market for conservation developments.

The study debunks a myth that people want big homes and big lots, and it suggests residential alternatives that could be hugely popular if marketed properly, says Rachel Kaplan, professor of environment and behavior at the School of Natural Resources and Environment.

Kaplan co-authored the study with her husband, Stephen Kaplan, a professor with joint appointments in electrical engineering and computer science and psychology; and Maureen Austin, assistant professor of environmental science and outdoor studies at Alaska Pacific University.

The study also shows that misuse and misunderstanding of the term "open space" fuels the myth that people prefer big lots.

The scientists surveyed residents in 18 subdivisions in Hamburg Township in Livingston County, the fastest growing county in the state.

"The most significant thing that came out of this study is that the myth that big homes on big lots are what is most important to people—and therefore everything that happens is market-driven—is wrong," Stephen Kaplan says. "To finally show that this is not preferred by the people who live there is the last blow. While people who own big houses on big lots like them, even they placed a much higher priority on having a nature view from home."

Part of the solution is to define open space properly and use more accurate terminology altogether, the researchers say. For example, planners could use the term "conservation ordinance" rather than the misleading "open space ordinance" for areas marked for preservation from development.
—Laura Bailey, News Service

Pulsed dye laser therapy does not improve acne

Laser therapy is an appealing treatment for acne: minimal risk of side effects, no messy creams and no drugs.

Unfortunately, there also appears to be no benefit, at least with one type of laser treatment called pulsed dye laser therapy, according to research from the U-M Health System (UMHS). The study, which appeared in the June 16 issue of the Journal of the American Medical Association, found pulsed dye laser therapy was not effective in treating acne.

Many dermatologists already use lasers to treat various conditions, including wrinkles, scars and acne. However, few randomized, controlled clinical trials have examined the value of lasers for treating acne, and none show conclusively whether the treatments actually work.

"Lasers have the potential to be a safe and convenient treatment option—but only if it's effective. The only way to know how to advise patients is to objectively study these treatments," says lead study author Dr. Jeffrey Orringer, clinical assistant professor of dermatology at the Medical School and director of the Cosmetic Dermatology and Laser Center at UMHS. "Lasers may prove to effectively treat acne. This paper is not meant as an indictment of all laser therapy for acne. But we need rigor in our clinical trials."

The study was funded by the Babcock Endowment for Dermatological Research at U-M, ICN Pharmaceuticals Inc., a Dermatology Foundation Clinical Career Development Award in Dermatologic Surgery and the National Institutes of Health.

Other study authors, all from the Department of Dermatology, were Dr. Sewon Kang, associate professor; Ted Hamilton, research associate; Wendy Schumacher, research assistant; Dr. Soyun Cho, lecturer; Craig Hammerberg, lab supervisor; Gary Fisher, associate professor; Dr. Darius Karimipour, clinical assistant professor; Dr. Timothy Johnson, professor; and Dr. John Voorhees, chair and the Duncan and Ella Poth Distinguished Professor.
—Nicole Fawcett, UMHS Public Relations

A calculated risk for heart attack patients

When patients go home from the hospital after a heart attack or sudden chest pain episode, they often face an uncertain future and a lot of worry about whether another heart-related crisis is just around the corner.

Now, research may give these patients and their doctors a better sense of who's really at risk—and who can be reassured that they'll probably be fine.

In the June 9 issue of the Journal of the American Medical Association, an international group of researchers provided a simple way for doctors to calculate the chances that a particular patient will die within six months of going home from the hospital after a heart attack or unstable angina episode.

The calculating tool, which can fit on a pocket card or be programmed into an ordinary handheld personal digital assistant, is based on data from 22,645 patients treated at 94 hospitals in 14 countries. Its developers hope that doctors everywhere will adopt it as a way of guiding treatment decisions and counseling recommendations for patients.

The paper's first author, Cardiovascular Center Clinical Director Dr. Kim Eagle—the Albion Walter Hewlett Professor of Internal Medicine—explains that the risk-predicting tool could help doctors decide early on how aggressively to treat a particular patient, to reduce his or her risk of dying soon after being discharged from the hospital. He says it could ease the minds of many patients, while helping others face the reality of their situation.

The new tool is based on data from GRACE, the Global Registry of Acute Coronary Events. Doctors can enter data about a patient's individual characteristics, key vital signs and test results. The GRACE model then calculates that patient's risk based on the statistical model built into the tool. The GRACE prediction model is available online for free use by any clinician at http://www.outcomes-umassmed.org/grace.

The GRACE study is funded by an unrestricted educational grant from Aventis Inc. to the University of Massachusetts Medical School's Center for Outcomes Research. In addition to Eagle, the study's authors include former U-M cardiology fellow Dr. Michael Lim and authors from institutions throughout the world. U-M leads a cluster of local hospitals that report data to GRACE.
—Kara Gavin, UMHS Public Relations

Self-regulation, board action can douse potential executive 'flameout'

Boards must take a much more active role in reviewing the performance of nonprofit agency executives before many of them engage in behavior that could harm them, the organization or industry, says John Tropman, a professor in the School of Social Work and adjunct professor in the Business School.

Destructive behavior, or flameout, involves the inappropriate use of agency resources, embezzlement or sexual misbehavior—often a result when personal and agency control structure are not working well, he says. Flameout occurs when an executive goes down in flames; calamity occurs when that executive takes her or his family and agency with him; supercalamity occurs when a whole industry is affected.

Tropman's paper, "Flameout/Calamity in the Nonprofit Sector," appears in a special issue of the journal Administration in Social Work this summer.

"Because of Enron, Health South, Tyco and others, many people feel that executive misbehavior is simply limited to the business community. Nothing could be further from the truth," Tropman says. "Governmental figures are involved as well. From Grover Cleveland to President Clinton, the presidency has been touched by scandal—and that is just the 20th century. And there have been significant numbers of nonprofit executives who have lost their jobs and harmed their agency and sector."

Senior managers are pushed to succeed and are rewarded for it. It's important that they, as well as board members, be alert to the signs of impending calamity and move proactively to prevent such destruction, Tropman says. This involves self-regulation and board action to hold the person accountable before they flame out, or turn to self-destructive behaviors that are extremely inappropriate and harmful, he says.
—Jared Wadley, News Service

Half of head and neck cancer patients disabled by treatment

More than half of people treated for head and neck cancer were unable to return to work after treatment, according to a study led by researchers at the U-M Health System (UMHS).

Researchers looked at 384 people with head and neck cancer who were employed when they were diagnosed and found 52 percent reported work-related disability after cancer treatment. Results of the study were published last month in the Archives of Otolaryngology-Head and Neck Surgery.

Patients who had undergone chemotherapy were 3.5 times more likely to report disability, and patients who had had a neck dissection—surgery to remove lymph nodes in the neck—were twice as likely to be disabled. Worse pain scores also were linked to disability, with each 10-point decline on a standard pain scale leading to a 20 percent increase in the odds of disability. Patients on average were more than four years out from their initial diagnosis.

"Although chemotherapy and neck dissection appear to be associated with disability, patients should not opt out of these important treatments because of that. Decisions about treatment should be primarily concerned with ensuring survival and preventing recurrence. Still, disability and quality of life issues are secondary concerns and need to be addressed," says study author Dr. Jeffrey Terrell, associate professor of otolaryngology at the Medical School and a member of the Comprehensive Cancer Center.

Other authors from the area were Dr. Joseph Taylor, otolaryngology resident at UMHS; David Ronis of the VA Ann Arbor Healthcare System and School of Nursing; Karen Fow-
ler, VA Ann Arbor Healthcare System; Sonia Duffy, Department of Otolaryngology and VA Ann Arbor Healthcare System. Funding came from the National Institutes of Health SPORE grant, GlaxoSmithKline's Managed Care Forum and a U.S. Department of Veterans Affairs grant.

For more information on the U-M head and neck oncology program, visit http://www.cancer.med.umich.edu/clinic/headneckclinic.htm. For information on cancer treatment and research at U-M, call the Cancer AnswerLine at (800) 865-1125.
—Nicole Fawcett, UMHS Public Relations

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