Cold Spring Harbor Laboratory Scientists Discover New Gene That Prevents Multiple Types Of Cancer

A decades-old cancer mystery has been solved by researchers at Cold Spring Harbor Laboratory (CSHL). "We not only found a critical tumor suppressor gene, but have revealed a master switch for a tumor suppressive network that means more targeted and effective cancer therapy in the future," said CSHL Associate Professor Alea Mills, Ph.D. The study, headed by Mills, was published in the February issue of Cell.

Specifically, Mills' discovery identifies CHD5, a protein that prevents cancer, as a novel tumor suppressor, mapping to a specific portion of chromosome 1 known as 1p36. When CHD5 is not functioning properly the machinery within our cells that normally prevents cancer turns off. The ability of CHD5 to function as a master switch for a tumor suppressive network suggests that this gene is responsible for diverse forms of human cancers.

After locating the region where the tumor suppressor resided, the Mills team identified which genes in that area were responsible for tumor suppression. Results showed that reducing expression of a single gene --CHD5-- made cells that had been rendered slow growing by adding an extra copy of the region, grow like normal cells.

The findings of Mills' study will influence the future of cancer research. It shows that deletion of a part of 1p36 causes cancer and increased "dosage" of CHD5 triggers extra tumor suppression. One extra dose, or copy, caused cells to either stop dividing or to undergo cell suicide by switching on a battery of potent tumor protective machinery. This work indicates that pharmaceuticals that switch on CHD5 may provide a way to treat many types of human cancer.

The research team worked with mouse models so they could investigate gains and losses of the chromosome segment corresponding to human 1p36. To extend the research to human cancer, Mills collaborated with Stanford University researchers Dr. Hannes Vogel and Dr. Markus Bredel to study whether CHD5 also functioned as a tumor suppressor in humans. They discovered that glioma, a specific form of brain tumor, frequently had deletion of CHD5, demonstrating the important role of CHD5 in human cancer.

This research and discovery was funded largely by private sector donations which are important to support state-of-the-art research and discoveries that may not traditionally be funded by the government. "The advance by Dr. Mills and her team shows that CSHL's strategy of providing financial resources to outstanding young scientists pays off towards diagnosing and treating disease and human suffering," states CSHL President Bruce Stillman.

The paper's citation is:

Bagchi A., Papazoglu C., Wu Y., Capurso D., Brodt M., Francis D., Bredel M., Vogel H., Mills A.A. (2007) CHD5 is a tumor suppressor at human 1p36, Cell 128, February 9, 2007.

CSHL is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.

Cold Spring Harbor Laboratory
http://www.cshl.edu/

Pfizer's Sutent Receives FDA Approval To Include New First-Line Advanced Kidney Cancer Data In Label

Pfizer Inc said today that the U.S. Food and Drug Administration (FDA) has approved new labeling of Sutent(R) (sunitinib malate) which includes first-line treatment of advanced renal cell carcinoma (RCC), a type of advanced kidney cancer, based on results of a large Phase 3 trial which showed prolonged progression-free survival.

"Sutent is redefining the kidney cancer treatment landscape and is a promising option for patients and their families," said Dr. Charles Baum, vice president of Pfizer Global Research and Development. "We are committed to furthering our research of this innovative treatment in other patient groups such as breast and lung cancer, where improved treatments are needed."

Sutent was originally approved in January 2006 for the treatment of advanced kidney cancer under the accelerated approval provision, based on partial response rates and duration of response. With the new labeling, the accelerated approval has been converted to regular approval.

In a large, randomized Phase 3 trial, 750 treatment-naive patients with metastatic RCC received either Sutent or the comparator interferon-alfa (IFN infinity), the current standard of care. Key findings include:

-- Patients taking Sutent achieved a median progression free survival of 11 months -- more than double the 5-month median progression free survival observed with IFN infinity;

-- Sutent patients experienced a 5-fold higher objective response rate compared with IFN infinity in first-line RCC treatment (27.5% vs. 5.3%);

-- Overall, Sutent was generally well tolerated with fewer discontinuations from treatment than IFN infinity. Fewer patients discontinued the medicine because of treatment-emergent non-fatal adverse events (9% vs. 12%).

These study results were published in the January 11, 2007 issue of The New England Journal of Medicine.

"For many years, the options available for people with metastatic kidney cancer have been very limited," said Dr. Robert Motzer, lead investigator of the Phase 3 trial and attending physician at Memorial Sloan-Kettering Cancer Center. "To have such a high percent of patients respond to this treatment is remarkable and a sign of the significant benefit Sutent may bring to patients fighting this deadly cancer."

Side effects for Sutent in this Phase 3 trial were generally mild or moderate. The most common treatment-related adverse events of any grade were fatigue, diarrhea, nausea, altered taste, mucositis/stomatitis, hypertension, anorexia and bleeding.

In addition to approval for first-line treatment of advanced RCC in the US, Sutent is also indicated for the treatment of gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib mesylate.

About Renal Cell Carcinoma

Advanced renal cell carcinoma, or kidney cancer, is a relatively rare though serious disease and historically has been among the most therapy-resistant tumors. According to the American Cancer Society, the rate of people developing kidney cancer has been increasing every year for reasons that are currently not clear. In 2007, an estimated 51,190 new cases of kidney cancer will be diagnosed (31,590 in men and 19,600 in women) in the United States, and about 12,890 people (8,080 men and 4,810 women) will die from this disease.

Important Safety Information

Women of child bearing age who are (or become) pregnant during therapy should be informed of the potential for fetal harm while on Sutent.

Decreases in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) have been observed. Patients with concomitant cardiac conditions should be carefully monitored for clinical signs and symptoms of congestive heart failure.

Patients should be monitored for hypertension and treated as needed with standard antihypertensive therapy. CBCs with platelet count and serum chemistries should be performed at the beginning of each treatment cycle for patients receiving treatment with Sutent.

For more information on Sutent please visit http://www.pfizer.com.

Pfizer Inc
http://www.pfizer.com

Actions Taken On HPV Legislation In Florida, Illinois, Indiana, Virginia

The following highlights recent news of state actions on human papillomavirus vaccine legislation. Merck's HPV vaccine Gardasil and GlaxoSmithKline's HPV vaccine Cervarix in clinical trials have been shown to be 100% effective in preventing infection with HPV strains 16 and 18, which together cause about 70% of cervical cancer cases. FDA in July 2006 approved Gardasil for sale and marketing to girls and women ages nine to 26, and CDC's Advisory Committee on Immunization Practices later that month voted unanimously to recommend that girls ages 11 and 12 receive the vaccine. GSK in April plans to file for FDA approval of Cervarix, and it expects approval by the end of this year (Kaiser Daily Women's Health Policy Report, 2/1). Summaries appear below.

• Florida: Two bills (S 660, H 561) recently were introduced in the Legislature that would require girls ages 11 and 12 to receive HPV vaccines, the Miami Herald reports. If either bill passes, the vaccination requirement would go into effect next year and would affect about 60,000 girls in the state, according to the Herald. Parents would be able to opt out of the requirement. The legislation has not been debated and likely will be more difficult to pass in the House than in the Senate, the Herald reports. The legislation has faced opposition from some conservative groups, including the Florida Catholic Conference, which is advocating that parents be allowed to opt in to a program for the vaccine rather than opt out of a requirement. Martin Myers, director of the National Network for Immunization Information, said HPV vaccines are a "milestone in public health" but mandates that girls receive the vaccine "might be too fast." He added that there are "many moral, ethical and social issues that have not been fully discussed yet" (Caputo, Miami Herald, 2/6).
  
  
• Illinois: A bill (S 0010) introduced last week in the Senate would require girls ages 11 and 12 in the state to be vaccinated against HPV beginning in the 2009 school year, the Chicago Sun-Times reports. The bill would require public health officials to provide girls and their parents or guardians with written information about HPV's link to cervical cancer and about the vaccine's availability, according to the Sun-Times. Parents would be permitted to apply for an exemption for medical or religious reasons. Sen. Debbie Halvorson (D) estimated that it initially would cost $4 million to vaccinate the state's 18,000 uninsured girls ages 11 and 12, the Sun-Times reports (Baldacci, Chicago Sun-Times, 2/4).
  
  
• Indiana: The Senate Health and Provider Services Committee on Wednesday voted 11-0 to amend a bill (SB 327) that would have required girls entering the sixth grade to receive an HPV vaccine, the Indianapolis Star reports (Hupp, Indianapolis Star, 2/1). The legislation stated that students "may not be prevented from enrolling in, attending or graduating from school for the sole reason that the student has not been immunized" against HPV. The original version would have required every school beginning in the 2008-2009 school year to report how many girls have been vaccinated (Kaiser Daily Women's Health Policy Report, 1/24). Under the revised bill, parents and guardians of girls entering the sixth grade would receive a warning from the State Department of Health about the link between HPV and cervical cancer. The revised bill would make the vaccination optional and also would require parents to notify schools about vaccination decisions within 20 days of receiving the health department warning, the Star reports (Indianapolis Star, 2/1).
  
  
• Virginia: The House on Monday voted 80-17 to approve an amended version of a bill (HB 2035) that would require girls enrolling in the sixth grade in the state's public schools to receive an HPV vaccine, the AP/WTOP reports. The amendment allows parents or guardians to review information about the vaccine and opt out of the requirement. Exemptions already exist in the original version of the bill and allow parents to opt their children out of the vaccination for religious or medical reasons, the AP/WTOP reports. The state Senate passed a similar bill on Friday without the parental opt-out provision (Potter, AP/WTOP, 2/5).
  

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Wall Street Journal Examines Studies Finding Increased Risk Of Premature Death After Ovary Removal

The risks associated with surgery to remove a woman's ovaries could outweigh the surgery's benefits -- primarily eliminating the development of ovarian cancer -- recent research suggests, the Wall Street Journal reports. About 300,000 women annually undergo surgery to remove their ovaries in an effort to decrease their risk of developing ovarian cancer. However, recent research indicates that such surgery can increase women's risk of dying from other causes, including heart attacks and hip fractures, according to the Journal. A Mayo Clinic study published last fall in the Lancet found that removing ovaries from women ages 45 and younger increased their risk of death by 70% during the next 30 years if they did not use hormone-replacement therapy. A second study published in the journal Obstetrics & Gynecology also showed that removing women's ovaries before age 65 increased their overall risk of death before age 80 by 8.5%, the Journal reports. The data from the studies were surprising because they "directly contradic[t] the widely held belief in the medical community that removing a woman's ovaries typically will prolong her life," the Journal reports. Women with a family history of ovarian cancer "obviously have more to gain" from ovary removal surgery than women with a family history of heart disease or osteoporosis, according to the Journal. William Parker -- professor of obstetrics and gynecology at the University of California-Los Angeles David Geffen School of Medicine and lead author of the Obstetrics study -- said that the study was not conclusive but that it should encourage a more serious discussion between patients and their physicians about the surgery (Parker-Pope, Wall Street Journal, 2/6).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Major Player In Cell Growth Identified By Cancer Biologists

When cells go about the business of dividing, they can get sidelined. Maybe there aren't enough nutrients. Maybe there aren't the right signals to resume multiplying. Either way, cells go quiet.

What can restart cell division -- the process that drives the development of embryos, the renewal of hair, skin and blood, and the creation of cancer -- is a single transcription factor called GABP, according to new research from The Warren Alpert Medical School of Brown University and Rhode Island Hospital.

The work, published online in Nature Cell Biology, introduces a new pathway that can be manipulated to control cell growth. Since cell growth is a fundamental biological process, the research may shed light on everything from miscarriages to muscular dystrophy. The main application, however, is cancer. Since a key characteristic of cancer cells is unchecked growth, the research identifies potential targets for new treatments.

"As a scientist and a physician, I am tremendously excited," said Alan Rosmarin, M.D., an associate professor in the Department of Medicine and the Department of Molecular Biology, Cell Biology and Biochemistry at Brown and director of clinical oncology research for Lifespan, Rhode Island's largest health care system. "This discovery not only adds to our basic understanding of cell division, it could lead to better cancer drugs. And they're needed. Cancer touches everyone."

During the cell cycle, the four-phase process of cell division, there is a period when the biochemical brakes are put on and cells become inactive. Then the process is kick-started and cells move into the so-called S phase, when DNA is duplicated. This is a critical juncture. If genes are missing or broken, these alterations are passed on to the new cell -- and could result in disability or in diseases such as cancer.

So biologists are keenly interested in identifying the accelerators that rev-up cell division. Ets transcription factors, a family of gene-regulating proteins that are major players in embryonic and cancer development, seemed obvious culprits. Rosmarin, a hematologist-oncologist, studies one member of the Ets family called GABP. This transcription factor helps make a variety of cells, including white blood cells. If those cells develop abnormally, leukemia results.

But the exact function of GABP in the cell cycle wasn't known. Rosmarin wanted to find out. So he and members of his laboratory created mice that carried a mutation -- tiny DNA sequences were inserted into their GABP-making gene. These DNA bits would serve as a time bomb of sorts, deleting a critical piece of the gene when given a chemical signal.

From these mice, Rosmarin and his team grew fibroblasts -- common connective tissue cells -- in a Petri dish with nutrient-rich serum and watched them grow. When they detonated their time bomb, GABP was disrupted, and the fibroblasts' ability to divide was dramatically reduced. At the same time, other genes known to restart cell division were unchanged.

The team confirmed GABP's critical role in cell growth another way. Simply forcing dormant cells to make GABP, they found, was enough to rouse cells from their slumber and get them to grow again.

"So we've found a new pathway to control cell growth," Rosmarin said. "Now that we know a way to disrupt GABP and stop division, there is the possibility that a drug can be made to do the same thing in cancer cells."

###

Zhong-Fa Yang, an instructor in medicine at Brown and a postdoctoral research fellow at Rhode Island Hospital, was the lead author of the journal article. Stephanie Mott, a Rhode Island Hospital research associate, assisted with the experiments.

The National Heart, Lung and Blood Institute, the National Center for Research Resources and the Herbert W. Saint '49 Fund at Brown University funded the work.

Contact: Wendy Lawton
Brown University

Nanotransport Deliver Pharmaceutical Agents To Tumor

To accurately transport pharmaceutical agents to their specific target organs or cell types, you need a good carrier: nanoscopic capsules with surface elements that can "recognize" the target in question could do the trick.

To date, all methods for the production of such tiny capsules require preorganized structures or "molds" to shape hollow spheres and most methods require a lengthy, tedious synthetic or purification procedure. Korean researchers led by Kimoon Kim have now developed a very simple novel approach for the direct production of polymeric nanocapsules. As described in the journal Angewandte Chemie, this method is generally applicable to any monomers as long as they have a flat core and multiple polymerizable groups at the periphery. Additionally, if building block are chosen that are able to bind specific (bio)molecules very tightly, the surface of the capsule can be easily decorated with species that are recognized by cells, showing the transporter the way to reach its goal, such as a tumor cell.

To demonstrate the power of their new concept, Kim and his team chose rigid, disk-shaped monomers equipped with a ring of special molecular "hooks" that can be activated by UV light. When a solution containing these disks is irradiated, the hooks grab on to each other, linking the disks into little, two-dimensional "patches" that in turn hook on to other patches. Once they reach a certain size, the patches bend around and close off to form hollow spheres, which can then be filled with guest molecules. The size of the spheres is very uniform and depends largely on the solvent in which the linking reaction takes place. The researchers used this method to produce capsules with diameters ranging from 50 to 600 nm.

The little disks used in this process deserve special consideration: Kim and his colleagues chose to use curcurbiturils. These disk-shaped molecules have a cavity at their center. As their shape resembles a hollowed-out pumpkin, this class of compounds was named after the plant genus of pumpkins, the cucurbitaceae. When the mini-pumpkins are linked together, they form an empty sphere with many tiny cavities on its surface. These "pockets" can be filled with certain nitrogen-containing biomolecules, such as spermine, in a very stable fashion.

The Korean researchers coupled spermine to the vitamin folic acid and packed these hybrid molecules into the capsule's pockets. This gave them capsules with a surface covered with folic acid molecules. What for? Many tumors have a significantly increased number of folic acid receptors on the surfaces of their cells. The folic acid on the capsules docks into these sites and is brought into the interior of the cell. Here, the contents of the capsule, such as an antitumor drug or contrast agent, can be released to selectively attack the tumor or to make an unambiguous diagnosis.

###

Author: Kimoon Kim, Pohang University of Science and Technology (Republic of Korea), http://css.postech.ac.kr/

Title: Direct Synthesis of Polymer Nanocapsules with a Noncovalently Tailorable Surface Angewandte Chemie International Edition, doi: 10.1002/anie.200604526

Contact: Kimoon Kim
John Wiley & Sons, Inc.

The Multi-Tasking Reovirus Kills Cancer Cells And Primes The Immune System

In the past couple of years, researchers at Oncolytics Biotech have been developing a harmless virus as a potent cancer killer, but they have also been accumulating data that suggests in addition to directly killing tumor cells, the reovirus may prime the immune system to mount a separate, powerful and long lasting defence against cancer.

Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic & Research Surgery Conference in Cambridge, U.K., in which she described a test tube experiment further supporting this claim. Fraser's presentation, titled "Reovirus as a Potentially Immunogenic as well as Cytotoxic Therapy for Metastatic Colorectal Cancer," reported how cells taken from a colorectal cancer liver metastases were more susceptible to death many weeks after treatment with reovirus, and long after the virus had cleared the patient's system. These cells, when cultured in the laboratory, also appeared to be vulnerable to re-infection with reovirus. Moreover, Dr. Fraser noted that dendritic cells, which prime the immune system against cancer, were activated by exposure to the reovirus.

"We understand how the reovirus replicates within and kills cancer cells," explains Dr. Matt Coffey, Chief Scientific Officer at Oncolytics, "but we also observed that tumors sometimes continue to shrink long after the virus is gone." Immunologic work now suggests that reovirus exposure is "educating" the immune system to recognize and kill the same cancer cells that were attacked by reovirus. "If you can teach the immune system to recognize cancer cells," says Coffey, "it may be possible to fight off the disease for much longer than we originally anticipated."

Late in 2006, another collaborator, Dr. Alan Melcher of the Cancer Research UK Clinical Centre in Leeds, hypothesized that reovirus activation of dendritic cells, which are key to early detection of infection (through the innate immune response), may "instruct" cells belonging to the adaptive immune response, namely natural killer cells and T cells, to attack the tumor even after the virus no longer remains in the body. That poster was presented at the European National Societies of Immunology Meeting in Paris.

Interestingly, another study conducted in 2006 at the Mayo Clinic suggested that momentarily suppressing the immune system allows the virus to continue replicating, leading to increased cancer cell killing. This in turn leads to the creation of more tumor antigens (the elements that educate the immune system), thereby increasing the vaccinating effect of the virus and perhaps improving the efficacy of oncolytic virus therapy.

"The apparent dual mechanism of action for oncolytic viruses will need to be tested further, both in patients and in the laboratory. If the effects turn out to be genuine, the implications for long-term survival from many types of cancer could be significant," says Coffey. Researchers believe that therapies working simultaneously, but through different mechanisms, may overcome the resistance to treatment that is typically seen in cancer. In addition, this double attack on cancer could point to new treatment regimens based on conventional therapies like radiation and chemotherapy with biological agents.

###

Contact: Cathy Ward
Oncolytics Biotech Inc.

Europe's Aging Population Causing Major Increase In Cancer Burden Experts Warn

Between 2004 and 2006, the number of new cases of cancer diagnosed each year in Europe has increased by 300,000 according to new estimates published in a report in Annals of Oncology [1]. It is estimated that in 2006 there were 3.2 million new cases of cancer (up from 2.9 million in 2004) and 1.7 million deaths from the disease in the whole of Europe.

Professor Peter Boyle, Director of the International Agency for Research on Cancer (IARC) in Lyon, France, who prepared the report with IARC colleagues, warned that despite better prevention and treatments, Europe faced a major increase in the cancer burden because of the ageing population. He said urgent action was needed now to tackle cancer, particularly in Central and Eastern Europe, through measures such as tobacco control and more widespread screening for breast and colorectal cancer, as well as efforts to improve people's diet and exercise and reduce levels of obesity.

"With an estimated 3.2 million new cases (53% occurring in men, 47% in women) and 1.7 million deaths (56% in men, 44% in women) each year, cancer remains an important public health problem in Europe, and the ageing of the European population will cause these numbers to continue to increase, even if age-specific rates of cancer remain constant," he said. "Evidence-based public health measures, such as screening, exist to reduce deaths from breast, cervical and colorectal cancer, while the incidence of lung cancer, and several other forms of cancer, could be diminished by tobacco control."

The 25 EU countries accounted for nearly 2.3 million of the new cases and over one million cancer deaths [2].

Lung, colorectal, breast and stomach cancers are the top four killers

Lung cancer remains the biggest killer, with an estimated 334,800 deaths in 2006 (19.7% of the total number of deaths from cancer), followed by colorectal cancer (207,400 deaths), breast cancer (131,900 deaths) and stomach cancer (118,200 deaths).

"Lung cancer retains its status as the leading cause of cancer death in Europe in 2006," said Prof Boyle. "The overwhelming majority of lung cancer is caused by tobacco smoking, and tobacco control is clearly a number one priority in Europe, not only aimed at men, particularly the male populations of Central and Eastern Europe, but increasingly targeted towards women, especially in Northern Europe."

Breast, colorectal and lung cancers have the highest incidence

Since the previous estimates for 2004, breast cancer has overtaken lung cancer as the commonest cancer to be diagnosed overall, with 429,900 new cases in 2006 (13.5% of all cancer cases). It was followed by colorectal cancer (412,900 cases, 12.9%) and lung cancer (386,300 cases, 12.1%).

Prof Boyle said the rise in the number of breast cancer cases could be attributed partially to the introduction of organised mammography screening programmes, which meant that more cancers were detected, and at an earlier stage. "These programmes have the short-term consequence of increasing the incidence, which has risen by 16% since our latest 2004 estimates." Despite the benefit of screening programmes, he said that deaths from breast cancer were continuing to rise (130,000 in 2004, 131,900 in 2006) because of the ageing population.

In women, after breast cancer, colorectal cancer (195,400, 13.1% of the total) and cancer of the uterus (149,300, 10%) were the most commonly diagnosed cancers.

In men, the widespread use of the Prostate Specific Antigen (PSA) tests was also having an effect on the numbers of prostate cancers being detected; prostate cancer was the most frequent cancer diagnosed (345,900, 20.3% of the total), followed by lung cancer (292,200, 17.2%) and colorectal cancer (217,400, 12.8%).

Prof Boyle said: "Despite the widespread use of PSA testing in many European countries, the number of deaths from prostate cancer has increased by around 16% since 1995 due, in large measure, to the rapid increase in the numbers of men reaching older ages."

Screening programmes needed

The second most common cause of cancer death in both men and women was colorectal cancer. "There remains hope that dietary modifications, increased physical activity and avoidance of obesity could lead to reductions in the incidence and mortality from colorectal cancer," said Prof Boyle. "However, progress has been very slow; the number of deaths has increased by 1.8% since our previous 2004 estimates. Screening for colorectal cancer has been shown to be effective, and clearly there is a need for organised colorectal cancer screening programmes throughout Europe."

Deaths from stomach cancer are continuing to decline in men and women throughout Europe, although it still accounts for 5.6% of all new cases of cancer (5.9% in 2004) and 7.4% of all cancer deaths (8.1% in 2004). "However, higher incidence and mortality rates occur in the Central and Eastern European countries, possibly reflecting a lower level of affluence, a diet lower in fresh fruits and vegetables and higher rates of Helicobacter pylori infection," said Prof Boyle.

Significant differences in the chances of surviving other cancers existed between the Eastern and Baltic European countries and other European countries. In the 25 member countries of the European Union an estimated 23,600 women died from cancer of the uterus in 2006 and 46,600 died in the whole of Europe.. "The number of years of life lost could be reduced in women living in Central and Eastern European countries if efficient national cervical cancer screening programmes were in place," said Prof Boyle.

He concluded: "The increased burden of cancer incidence in Europe between 2004 and 2006, which is estimated to have risen by 300,000 to 3.2 million, demonstrates the impact of the ageing of the European population and underlines the need for active and effective tobacco control measures and screening programmes in Europe."

###

[1] Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology. doi:10.1093/annonc/mdl498 [2] In 2006 the European Union comprised: Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, The Netherlands and United Kingdom. Europe comprised the 25 EU countries plus Albania, Belarus, Bosnia Herzegovina, Bulgaria, Croatia, Iceland, Macedonia, Moldova, Norway, Romania, Russian Federation, Serbia and Montenegro, Switzerland, Ukraine.

Contact: Emma Mason
European Society for Medical Oncology

African-Americans Receive Fewer Stem Cell Transplants Than Whites

Lower transplant rates in ethnic communities may be explained somewhat by a lack of suitable anonymous donors, a problem the medical community has long known and been working to address. Surprisingly, the study found the discrepancy in treatment held true even when the transplant was autologous (e.g. self-donated stem cells were used) or when the cells were donated by a relative, typically a sibling.

"The National Marrow Donor Program has made great strides in increasing the number of African-American donors, which is important because non-related donors are more likely to have a tissue type that matches the patient if they are of the same ethnic group," said Mary Horowitz, M.D., M.S., chief scientific director for the Center for International Blood and Marrow Transplant Research (CIBMTR) and professor of medicine at the Medical College of Wisconsin, Milwaukee. "But our research shows the problem is more extensive than we thought, and if all we do is increase the number of available anonymous donors, we won't be successful in making sure that everyone who needs transplant gets one. While the shortage of appropriate anonymous donors is an understandable cause of a lower rate of unrelated donor transplantation, it should not affect the use of autologous or related donor transplants in African-Americans, yet the rates of these transplants are also lower."

Stem cell transplant (also known as blood and marrow transplant) is used to treat diseases of the blood and several types of cancer. In the study, researchers looked at the rate of stem cell transplants among African-Americans, Caucasians and men and women for the treatment of three types of cancer most commonly treated with stem cell transplants: leukemia, lymphoma and multiple myeloma. Together, these cancers account for nearly 10 percent of all cancer cases in the United States.

Patients who are candidates for stem cell transplants are most likely to find a matching donor in someone of their own ethnicity. The group of genes known as human leukocyte antigens (HLA) in the donor and patient must be closely matched for the procedure to be successful, and that is more likely to be true within ethnic groups. Because African-Americans have a greater variation of HLA types, it is estimated that three times as many African-American donors are needed to equal the chance of obtaining a Caucasian match, according to the National Cord Blood Program.

The next step is for researchers to determine why the stem cell transplant self-donation and relative-donation rates differ between Caucasians and African-Americans. Among the potential reasons:

* Differences in insurance coverage for sophisticated or aggressive health care treatments, including stem cell transplants

* The effect of cultural attitudes toward the medical system

* Physicians attitudes toward minorities

* Bias among doctors and patients; for instance, doctors may make assumptions about how different communities feel about aggressive therapy, including stem cell transplants

"The National Marrow Donor Program and the Center for International Blood and Marrow Transplant Research are interested in exploring the reasons for the discrepancy, and may conduct focus groups regarding barriers to participation in transplantation among minorities," said J. Douglas Rizzo, M.D. M.S., associate scientific director of CIBMTR and associate professor of medicine at the Medical College of Wisconsin.

The study also looked at gender differences and although men were somewhat more likely than women to receive autologous stem-cell transplants, the difference wasn't striking and may be just a statistical anomaly, said Dr. Horowitz.

Previous studies have shown that African-Americans are more likely to be diagnosed at advanced stages of cancer and less likely to receive optimal care than Caucasians.

Stem cells are progenitor cells in the bone marrow and blood stream, meaning they can develop into a number of different cell types. Stem cells can be damaged by disease, such as cancer, or treatment, such as chemotherapy or radiation. Stem cell transplant involves taking the cells from healthy donors and infusing them in the ill patient, where they can reproduce more healthy stem cells and strengthen the patient's immune system. Stem cells may be collected, or harvested, directly from the bone marrow, or from the circulating blood and infused into the patient's bloodstream. In addition to being donated anonymously or by a relative, stem cells can sometimes be self-donated. That is, they are removed from the patient, conditioned, and reinfused in the patient after chemotherapy or other stem cell-destroying treatment.

###

The BMT Tandem Meetings are the joint annual meetings of two leading professional organizations dedicated to research, education and patient care in the field of blood and marrow transplantation and cellular therapy. The American Society for Blood and Marrow Transplantation (ASBMT), based in Arlington Heights, Ill., is a professional association of clinicians, investigators and other health personnel promoting blood and marrow transplantation research, education, scholarly publication and clinical standards. The Center for International Blood and Marrow Transplant Research (CIBMTR), based in Milwaukee, is an affiliation of the International Bone Marrow Transplant Registry (IBMTR) of the Medical College of Wisconsin and the research arm of the National Marrow Donor Program, which collects, analyses and disseminates clinical data on blood and marrow transplantation and conducts original research to determine the most effective BMT strategies.

Contact: Lindsay Kahn
Medical College of Wisconsin

Study Examines Second Cancer Risk Among Hairy Cell Leukemia Survivors

Survivors of a rare cancer called hairy cell leukemia are at an increased risk of Hodgkin lymphoma, non-Hodgkin lymphoma, and thyroid cancer, and at an increased risk of death from leukemia and lymphoma, according to a new study. However, the absolute risk of those second cancers is small.

Hairy cell leukemia is a malignancy of a type of white blood cell called B lymphocytes. It accounts for about 2 percent of all leukemias. Better treatments have improved the prognosis for this disease, but the treatments may be associated with an increased risk of second cancers. To determine the risk of second cancers and to examine the causes of death among these patients, Michie Hisada, M.D., Sc.D., and colleagues at the National Cancer Institute examined the records for 3,104 patients with hairy cell leukemia who survived for at least two months after diagnosis.

They found that hairy cell leukemia survivors had a 6.6-fold increased risk of Hodgkin lymphoma, a 5-fold increased risk of non-Hodgkin lymphoma, a 3.6-fold increased risk of thyroid cancer, but a decreased risk of lung cancer compared with the general population. Among survivors, there was a lower risk of death from cardiovascular and cerebrovascular diseases than among the general population. "… Extrapolating from our results, among 10,000 hairy cell leukemia patients, a total excess of about 34 cancers - 21 non-Hodgkin lymphomas, 2 Hodgkin lymphomas, and 7 solid tumors (including two thyroid cancers) - might be observed per year," the authors write.

"Future studies should address the influence of such factors as changes in treatment regimens, immunologic impairment, natural history, diagnostic misclassification, and tobacco use on risk of second cancers in hairy cell leukemia patients," the authors conclude.

###

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Other highlights in the February 7 JNCI

Contact: Liz Savage
Journal of the National Cancer Institute