PLCO Trial Publishes Baseline Findings

A multicenter randomized clinical trial to determine if screening for prostate cancer reduces mortality from the disease has published findings from the initial round of screening. The study is comparing men who receive annual prostate-specific antigen (PSA) testing and digital rectal exams (DREs) for 6 years with a control group that receives routine medical care.

"Everything about the study's findings should reassure people that the trial is on track and that if we are given enough time we will answer the question: Does prostate screening done in this way save lives?" says Dr. Gerald Andriole of Washington University School of Medicine. Because prostate cancer progresses slowly for many patients, he adds, it could take until the year 2019 to answer the question.

According to findings published in the March 16 Journal of the National Cancer Institute, of the 34,000 men in the screening group, about 7 percent had a positive DRE and about 8 percent had a positive PSA level. Of this group, 74 percent underwent additional diagnostic testing, and one-third had a prostatic biopsy within one year.

Overall, 1.4 percent of the men in the screening group were diagnosed with prostate cancer, most of which was clinically localized. A companion paper reporting on the first 3 years of this trial, which is part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, appears in the March issue of the Journal of Urology.

Maternal Smoking's Effects Found in Amniotic Fluid

Maternal smoking was associated with increased chromosomal damage in cells in fetal amniotic fluid, including breaks in a key gene associated with risk for leukemia, according to a Spanish study reported in the March 9 Journal of the American Medical Association.

Although previous studies have found tobacco-specific metabolites in fetal blood and amniotic fluid, there are no data on the potential genotoxic effects of tobacco on the embryo and fetus. Researchers at Universitat Autònoma de Barcelona compared amniotic fluid drawn from 25 nonsmoking pregnant women with 25 women who smoked during pregnancy.

"Our results show that fetuses exposed to tobacco smoke in utero have increased chromosomal instability in amniocytes, expressed as an increase of structural chromosomal abnormalities and chromosomal lesions," the researchers wrote. For example, the proportion of structural chromosomal abnormalities was 12.1 percent in smokers, compared with 3.5 percent among the controls.

The researchers found breakpoints among the smokers in three chromosome bands known to be sensitive to genotoxic compounds in tobacco. Most significant were breaks in band 11q23 that "are known to be involved in leukemogenesis." The scientists concluded, "The transplacental exposure to tobacco could be associated with an increased risk of pediatric hematopoietic malignancies."

Breast Cancer Survivors More Likely to Get Fractures

The protective effect of estrogen on bone health can be compromised in women who are treated for breast cancer because of surgery to remove their ovaries, chemotherapy-induced menopause, prohibition of hormone replacement therapy for those with hormone-responsive tumors, and the effect of cancer itself. To confirm whether these conditions translate into higher fracture incidence, researchers from the Women's Health Initiative Observational Study followed 5,298 breast cancer survivors for 5.1 years and monitored their first-event fractures. Their results are published in the March 14 Archives of Internal Medicine.

Compared with a reference group of 80,848 women, those who had been treated for breast cancer reported a higher incidence of bone fractures in their vertebrae, lower arm or wrist, and other regions of the body except for the hip. The trend - which showed an overall 15 percent increased risk of fractures for breast cancer survivors - persisted after adjusting for hormone therapy, previous fractures, lifestyle, medication use, age, ethnicity, weight, and geographic region of enrollment.

The authors point out that self-reported data on non-hip fractures and lack of information on breast cancer diagnosis and treatment are limitations of this study, but conclude, "If our…results are confirmed by others, the excess number of fractures may be as high as 13,000 per year for the two million postmenopausal breast cancer survivors in the United States."

New Tumor Suppressor Gene Discovered in Drosophila

Researchers at Penn State University have discovered a new tumor suppressor gene in the fruit fly Drosophila. Termed mats (Mob as tumor suppressor), this gene is the first member of the large Mob gene family that has been shown to play a critical role in inhibition of cell growth. The study, which appears in the March 11 Cell, also found that the protein encoded by mats is a co-activator of the Wts kinase, a known tumor suppressor protein. Mats and Wts have a synergistic effect in controlling cell growth and promoting apoptosis.

The researchers first identified mats as a mutant gene in a Drosophila line that had developed spontaneous tumors. Using genetic mapping techniques, they pinpointed the chromosomal location of the tumor-inducing gene and identified it as a member of the Mob family. Over 130 Mob members have been identified in a variety of organisms, although their cellular functions are not entirely understood. The researchers found that Mats could inhibit cell growth and promote cell death by interacting with several proteins, including the Wts kinase, enhancing kinase activity.

The researchers also found that introducing a normal mats gene into flies with a mutated copy could suppress tumor development. Introducing the human Mats gene into flies also produced the same effect. Mats mutations have been identified in human and mouse cancers, suggesting that this gene and others in the family may be a new class of tumor suppressors in mammals.