Old yeast brew new clues to cancer

Discovery in single-celled fungus may hold key to age-related cancer in humans

Fred Hutchinson researchers have made a landmark discovery in yeast that may reveal why growing older is the greatest cancer-risk factor in humans. Researchers found that, like human cells, yeast cells suffer genetic damage as they approach old age. The discovery sheds light on the mechanisms and molecules that may be relevant in age-related cancer development.

Dr. Dan Gottschling and graduate student Michael McMurray have found striking similarities between humans and simple baker’s yeast with regard to the changes their genes undergo as they age.

“While yeast don’t get cancer, they do have one of the major hallmarks of malignancy, which is genetic instability,” Gottschling said.“We found a similar thing in yeast that has been seen in humans: genetic instability shoots up dramatically in the middle to late stage of life.”

When yeast cells hit the equivalent of late-middle age, the researchers discovered they experience a sudden, 200-fold surge in the production of genetic changes typically manifested as loss of heterozygosity, a condition characterized by missing or mutated chromosomes.

“Yeast gives us, for the first time, the potential for not only understanding the principles of what’s going on mechanistically but also which molecules might be relevant to the process of age-related cancer development,” Gottschling said.

Nearly 80 percent of cancers are diagnosed after age 55. After reaching late-middle age, men face a 50 percent chance of developing cancer and women have a 35 percent chance. No one knows why cancer typically surfaces later in life, although a multitude of scientific theories abound. “This finding may provide scientists with a new tool to test those theories,” Gottschling said.

New test helps predict prognosis for leukemia patients in remission

A sensitive molecular test holds new hope for people with leukemia. The test, developed by Fred Hutchinson researchers and colleagues, precisely measures the extent of remission in cancer patients undergoing drug therapy and may help predict their likelihood of relapse.

The researchers predict the test will speed the delivery of new therapies to patients by reducing the length of clinical trials, the process used to test and compare cancer treatments.

In the study, Dr. Jerry Radich’s laboratory and collaborators used a molecular test to detect residual cancer cells in chronic myeloid leukemia patients. The test — which is based on a technique called polymerase chain reaction — proved to be far more stringent at picking up traces of cancer that could lead to relapse than the standard test, in which chromosomes are examined under a microscope.

Radich said that the study opens the door to using molecular diagnosis of remission as a surrogate endpoint for studies, which could reduce the duration and cost of conducting large-scale clinical trials.

“Rather than waiting five or 10 years to know how well a new therapy works, we can have answers in a year, which will make the best new therapies available faster and at less cost.”

Alcohol use increases risk of hormonally sensitive breast cancers

Older women with a history of alcohol use are significantly more likely than nondrinkers to be diagnosed with hormonally sensitive forms of breast cancer, according to a Fred Hutchinson study. Postmenopausal women who reported consuming at least the equivalent of two drinks a day had an 80 percent higher risk of breast cancer overall compared to nondrinkers.

The risk varied by cellular breast-cancer type. “Current consumers of two or more drinks per day had more than three times the risk of lobular cancer (a 330 percent increased risk) and a 50 percent increased risk of ductal cancer,” said Dr. Christopher Li, lead author of the study.

Moderate exercise reduces risk of breast cancer by 20 percent

Researchers have found that regular, moderate physical activity cuts breast-cancer risk and even reduces the risk for women on hormone-replacement therapy.

Increased physical activity, even when begun later in life, reduces overall breast-cancer risk by 20 percent among women at all levels of risk for the disease, according to a study led by Fred Hutchinson’s Dr Anne McTiernan. What’s more, the activity need not be strenuous, but it should be done consistently, such as taking a brisk, 30-minute walk five days a week.

“We thought it was important to determine if moderate-intensity physical activities, such as walking, biking outdoors or easy swimming, when initiated later in life, can reduce the risk of breast cancer, since these types of activities are achievable for most women,” said McTiernan. “Our results suggest that, indeed, moderate activity, even when started in a woman’s postmenopausal years, can cut her risk of breast cancer.”

In addition, the researchers found regular exercise causes a similar reduction in overall breast-cancer incidence among women considered to be at highest risk for the disease. These women include those with a strong family history of breast cancer, those who’ve never had children and those who take combination hormone-replacement therapy.

Heavy smoking doubles risk of aggressive prostate cancer

Middle-aged men who are long-term, heavy smokers face twice the risk of developing more aggressive forms of prostate cancer than men who have never smoked, according to a new Fred Hutchinson study.

Specifically, men under age 65 with a history of 40 or more “pack-years” (those who smoke a pack a day for 40 years or two packs a day for 20 years) of cigarette smoking face a 100 percent increased risk of developing aggressive forms of the disease, said Dr. Janet L. Stanford, senior author of the study. Such men also face a 60 percent increased risk of prostate cancer overall relative to nonsmokers.

Previously, research results on smoking and prostate cancer have been mixed. But these data, together with other recent studies, provide cumulative evidence that smoking — in particular high-dose, long-term cigarette exposure — is an important risk factor for prostate cancer, Stanford said.

“From a public-health perspective, I think we now have enough evidence to suggest that prostate cancer should be added to the long list of malignancies in which smoking plays a role,” said Stanford, director of the center’s Prostate Cancer Research Program. Other smoking-related cancers include those of the lung, bladder, cervix, esophagus and kidney.

Promising treatment for common childhood brain cancer

Vitamin A derivatives may be highly effective, minimally toxic treatments for medulloblastoma, the most common form of childhood brain cancer. Clinical trials of the drugs, known as retinoids, are expected to begin in about a year for a subset of children who are at high risk for tumor relapse following standard therapy.

Research led by Drs. Andrew Hallahan and Jim Olson showed that retinoids killed cancer cells from medullublastoma tumors that had been surgically removed from patients as well as tumors in mice. Through genetic analysis, the scientists also identified a protein in medulloblastoma cells that is triggered by retinoids to initiate cell death, a finding that is likely to lead to the development of additional therapies for the disease.

Because retinoids already have received approval from the U.S. Food and Drug Administration for treatment of another childhood cancer, neuroblastoma, researchers expect that the drugs will quickly enter clinical trials for pediatric medulloblastoma patients.

Petersdorf wins Asian American pioneer award

Clinical researcher Dr. Effie Petersdorf has received the 2003 Asian American Living Pioneer Award from the Northwest Asian Weekly Foundation in recognition of her pioneering efforts in medical research.

Petersdorf’s work has helped improve outcomes of patients who undergo bone-marrow or stem-cell transplants for leukemia by refining the tissue-typing process that enables cancer patients to find suitably matched donors. Petersdorf and colleagues have shown that certain donor-recipient mismatches can still lead to a successful transplant. The finding potentially widens the pool of available donors for those individuals for whom the donor pool is limited, particularly those of mixed-race heritage.

Previous recipients of the Pioneer award include Washington Gov. Gary Locke, KING-TV anchor Lori Matsukawa and Seattle philanthropist Scott Oki.