NCI recently released data from the Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer study, which could help identify genetic factors that influence the disease and affect development of new therapies.
"The immediate sharing of the database with the cancer research community will allow researchers to compare existing and developing information with CGEMS data to identify new genes associated with increased prostate cancer risk," said NCI Deputy Director for Advanced Technologies and Strategic Partnerships, Dr. Anna D. Barker.
CGEMS procured genetic samples of prostate cancer from more than 1,100 men with the disease and 1,100 men without it. The samples included over 680 million individual genotypes and 310,000 genetic variants. Finding genetic variations that differ in frequency between patient and control groups will help identify the location of multiple inherited genes that affect the risk of prostate cancer.
"CGEMS represents one of the first of a new generation of studies made possible by the Human Genome Project," added Dr. Gilles Thomas of NCI's Division of Cancer Epidemiology and Genetics and lead scientist of the project. "Through immediate data sharing, we hope to encourage other teams to make similar studies in cancer and other diseases rapidly accessible to speed progress in understanding the inherited causes of cancer."
Launched in February 2006, CGEMS is the largest comprehensive initiative to identify genetic risk factors for breast and prostate cancers, two of the most frequently diagnosed cancers in the United States. Similar data on breast cancer are now being generated and anticipated for release in early 2007.
CGEMS study data are available through NCI's cancer Biomedical Informatics Grid™) at http://caIntegrator.nci.nih.gov/cgems/.
A new population-based study suggests that multivisceral resection - a surgical procedure recommended for patients with colorectal cancer that has not metastasized but that has affected organs adjacent to the colon or rectum - is drastically underused. Failure to use the procedure was associated with poorer overall survival rates, the study found.
Published in the October 18 Journal of the National Cancer Institute (JNCI), the study used NCI's Surveillance, Epidemiology, and End Results (SEER) registry to review the care and outcomes of 8,400 patients who underwent surgery to remove colon or rectal tumors that had expanded into nearby organs. The study authors, led by Dr. Calvin H. L. Law of Toronto Sunnybrook Regional Cancer Center in Canada, noted that clinical guidelines recommend that such patients undergo multivisceral resection, which involves the removal of the tumor and the adjacent organs.
They found, however, that only one-third of patients included in the study - all of whom were treated between January 1998 and December 2002 - underwent multivisceral resection. The remaining patients had only the tumor removed, which the authors noted is a far less complicated procedure with fewer related morbidities. Patients who underwent multivisceral resection, however, had significantly greater 5-year survival rates (35.1 percent vs. 27.7 percent), and treatment with a multivisceral resection was independently associated with improved overall survival.
Several factors were associated with a greater likelihood of receiving multivisceral resection, the authors found, including being under age 80 and being female. There was also a significant variation in the likelihood of receiving the procedure based on the region of the country in which patients were treated.
Additional studies are needed, they concluded, "to elucidate factors related to the structures and processes of care that contribute to deficiencies in surgical care and to determine future interventions to improve the quality of care delivered to this patient population."
Researchers at the University of North Carolina (UNC) at Chapel Hill have discovered that Kaposi's sarcoma-associated herpesvirus (KSHV) may promote the development of malignant lesions in Kaposi's sarcoma (KS) patients by extending the lifespan of virally infected endothelial cells.
In KS lesions, expression levels of a KSHV protein, K1, vary widely. In order to determine the contribution of K1 to KS tumor progression, the investigators expressed K1 in primary human umbilical vein endothelial cells. They found that the K1-expressing cells survived for more than 200 days in culture, whereas cells expressing a control protein stopped dividing after about 130 days.
Lengthier endothelial cell survival was attributed to a fourfold increase in the secretion of vascular endothelial growth factor (VEGF) following K1-induced activation of gene transcription. VEGF stimulates proliferation of infected endothelial cells, as well as healthy neighboring cells, and fuels the growth of new blood vessels.
Two cell-signaling pathways, VEGF/VEGFR-2 and PI3K/Akt, which enhance cell survival by promoting growth and inhibiting apoptosis, were also highly activated in K1-expressing endothelial cells. In mouse models, the researchers observed that K1 enhances epithelial tumor vasculature and size.
Protein expression changes that affect cell growth control or the ability of cells to invade deeper tissues, such as those provoked by K1, can lead to the development of cancer.
"Understanding how K1 functions may help us understand the pathogenesis of KSHV-associated malignancies and how KSHV functions as a tumor virus in the human population," noted Dr. Blossom Damania, who presented the findings October 16 at the NCI-sponsored 10th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies, held in Bethesda, Md.
Radiation exposure has been linked with the occurrence of some childhood cancers, and radiotherapy treatments for children with certain cancers may also cause a second primary malignancy. New findings published in the October 18 JNCI suggest that women who were exposed to radiotherapy during treatment for childhood cancer - especially pelvic radiation - are more likely to deliver infants who are born prematurely (defined as less than 37 weeks gestation) and who have a low birthweight (less than 5.5 pounds).
The data resulted from a new analysis of the ongoing, long-term Childhood Cancer Survivors Study, an NCI-funded longitudinal cohort study of some 20,000 survivors of childhood cancer, with more than 4,000 of their siblings used as controls. Dr. Lisa B. Signorello of the International Epidemiology Institute of Rockville, Md., and colleagues looked at the live children born to 1,264 survivors and 601 controls between 1972 and 2002.
When the cumulative radiation their mothers had received exceeded 500 centigrays (cGY), babies were 3.5 times more likely to be born preterm than were babies born to women who received no radiation. Irrespective of treatment, survivors' risk of giving birth preterm was 21 percent, 1.9 times that for controls. Kidney cancer was the original disease most likely to be associated with preterm birth. There was little or no risk associated with chemotherapy.
While conceding that "the etiology of preterm birth is largely unknown...[and] the mechanism is likely multifactorial," the authors concluded that "the adverse association between uterine irradiation and the risk of future preterm birth might be especially important for girls who receive such treatment before menarche."
In an accompanying editorial, Dr. Leslie R. Schover of the University of Texas M.D. Anderson Cancer Center added that "we should design professional education materials that map out the paths to making informed decisions."