NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
January 31, 2006 • Volume 3 / Number 5 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Notes
Request for Information on Knockout Mice
NCI is participating in a trans-NIH effort to acquire as many of the published strains of knockout mice as possible for deposition in public repositories. The NCI research community is invited to help NIH in this process by nominating strains from a list of potentially available strains. Instructions for participating can be found in Request for Information NOT-DA-06-008, which will be posted soon at http://grants.nih.gov/
grants/guide/index.html
. The deadline for responses is February 7.

NCI Funding Policy Available Online
Information about NCI's official funding policy for FY 2006 Research Project Grants (RPGs) is available online at http://deainfo.nci.nih.gov/
grantspolicies/Final
FundLtr.htm
. Information about the major RPG funding mechanisms for competing and noncompeting awards is included. Information about funding policies for other institutes can be found online at http://grants.nih.gov/
grants/financial/index.htm
.

Surgical Expertise and Patient Outcomes After Ovarian Cancer Surgery

Two companion studies, published in the February 1 Journal of the National Cancer Institute, examined whether outcomes after ovarian cancer surgery were influenced by the specialty training of the surgeon, or the number of procedures performed either by the surgeon or in the individual hospital. These NCI-sponsored studies were led by Drs. Deborah Schrag at Memorial Sloan-Kettering Cancer Center and Craig Earle at Dana-Farber Cancer Center, in collaboration with investigators at NCI and the Society of Gynecologic Oncologists. This study was stimulated by prior research indicating that some women with ovarian cancer are not receiving optimal care.

Both studies included women aged 65 or older with ovarian cancer who were reported to NCI's Surveillance, Epidemiology, and End Results registries between 1992 and 1999, and had available corresponding Medicare claims. One study focused on surgical specialty and utilized data on patients' sociodemographic characteristics, stage of disease, and comorbidities to assess whether evidenced-based care was received. Other outcomes assessed included surgical complications, short-term surgical mortality, and overall survival.

Patients were significantly more likely to receive evidenced-based care when treated by a gynecologic oncologist than by a gynecologist or general surgeon. Survival rates were higher among patients treated by a gynecologic oncologist or general gynecologist than by a general surgeon. The authors state, "Ovarian cancer patients treated by gynecologic oncologists had marginally better outcomes than those treated by general gynecologists and clearly superior outcomes compared with patients treated by general surgeons."

The second study examined whether the procedure volume of the surgeon or the associated hospital influenced outcomes. Measurements of outcomes included 60-day and 2-year postoperative mortality and overall survival.

Neither surgeon nor hospital procedure volume significantly influenced 60-day mortality although hospitals that performed higher volumes of procedures did have significantly lower 2-year mortality. The investigators concluded that neither hospital nor surgeon procedure volume was strongly associated with overall survival. These findings suggest that specialized training, more than surgeon volume, improved patient outcomes. The authors conclude that data from these two studies support that it is preferable for patients with ovarian cancer to be operated on by gynecologic oncologists when possible.

Methylation and Silencing of a Tumor-Suppressor Gene

While it is common knowledge that genetic mutations can lead to cancer, the importance of epigenetic events - chemical changes that affect gene expression - is now coming to the forefront of cancer research. DNA methylation is an epigenetic mechanism commonly involved in the control of gene expression and chromosome stability. Abnormal methylation of a gene can silence tumor suppressor genes or activate oncogenes, leading to tumor formation.

A study published in the January 24 Proceedings of the National Academy of Sciences identifies a probable tumor suppressor gene that is silenced when overmethylated, leading to aggressive cellular behavior. The investigators isolated this gene, TCF21, from patients with lung cancer, or with head and neck cancer. The gene is a transcription factor that plays an important role during embryogenesis, helping immature mesenchymal cells differentiate into mature epithelial cells. Investigators found a statistically significant difference in methylation of this gene between tumor and normal cells, both in samples taken from patients and in established cell lines.

When TCF21 was silenced, cells reverted to less differentiated behavior, including an increased ability for migration and increased cell division. Treatment of cell lines in which TCF21 was methylated and silenced with decitabine, a drug that can demethylate genes, reactivated TCF21. "Because this gene is silenced by DNA methylation," says first author Dr. Laura Smith, of Ohio State University, in an accompanying press release, "it might be possible to reactivate it using drugs that reverse the methylation process. This could provide a new strategy for treating these cancers."

Omega-3 Fatty Acids Unlikely to Prevent Cancer

An analysis of numerous, large population cohort studies did not detect evidence of a significant link between dietary intake of omega-3 fatty acids (found in fish) and the incidence of several major cancer types, according to a review study published in the January 25 Journal of the American Medical Association.

The reviewers analyzed 38 articles covering 20 population cohorts that included more than 700,000 individuals. The participants were studied for the effects of consuming omega-3 - either in fish, dietary supplements, or both - on the incidence of 11 different types of cancer, although more than half of the reports were for either breast, colorectal, or prostate cancers.

The combined studies provided 65 estimates of associations between omega-3 and cancer incidence, but "only 10 were statistically significant," reported the researchers led by Dr. Catherine H. MacLean with RAND Health. Significant associations between omega-3 fatty acid consumption and cancer risk were reported for breast, colorectal, lung, prostate, and skin cancers. "However, for breast, lung, and prostate cancer, there were significant associations for both increased risk and decreased risk and far more estimates that did not demonstrate any association," the researchers noted.

Across the cohorts, no trend was found linking omega-3 fatty acids with a reduced overall cancer risk. "Likewise, there is little to suggest that omega-3 fatty acids reduce the risk of any single type of cancer," the authors wrote.

Nasopharyngeal Meta-Analysis Shows Chemotherapy Works

Nasopharyngeal cancer (NPC) is rare in the United States and Western Europe, but endemic in many areas of the world (including China, Southeast Asia, North Africa and the Middle East), where it is strongly associated with the Epstein-Barr virus. Standard treatment for locally advanced disease is radiation therapy. While chemotherapy is often used as well, 11 large international trials failed to produce definitive evidence of additional benefit.

A meta-analysis using updated individual data from 1,753 patients in 8 of the trials confirmed that adding chemotherapy, especially during the course of radiation therapy, improved overall survival by 18 percent compared with those receiving radiation alone. Event-free survival improved by 24 percent.

Writing in the January 1 International Journal of Radiation Oncology·Biology· Physics, Dr. Bertrand Baujat, of the Institut Gustave-Roussy in Villejuif, France, and colleagues say the treatment effect is "small, but significant."

Cisplatin plus 5-fluouracil proved to be the best chemotherapy regimen, though the data demonstrating this were not uniform across all trials, nor as consistently strong for overall survival as for event-free survival. Subgroup analyses of those patients receiving chemotherapy before and after radiation therapy showed no significant advantage.