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Tatie
Posts: 28
Joined: Aug 2003

CHICAGO – A gene present in nearly one in eight people is the most commonly inherited cancer susceptibility gene identified so far, increasing cancer risk in carriers by 26 percent, according to a study published by researchers at Chicago's Northwestern Memorial Hospital in today's Journal of Clinical Oncology. More common than the BRCA gene mutations, Transforming Growth Factor Beta Receptor 1*6A (TGFBR1*6A) may increase risk of breast cancer by 48 percent, ovarian cancer by 53 percent, and colon cancer by 38 percent.

"This is an exciting finding because TGFBR1*6A is a common gene that may cause a large number of cancers. In the near future, it will be commonplace for people to know what genes make them more susceptible to cancer, and we'll have many more options for preventing those cancers," says Boris Pasche, M.D., Ph.D., F.A.C.P., director of Northwestern's Cancer Genetics Program, assistant professor of medicine at the Feinberg School of Medicine and a researcher at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Researchers analyzed seven published studies and pooled those results to conclude that the TGFRB1*6A gene may be to blame for approximately 7 percent of all breast cancers, nearly 11 percent of all ovarian cancers and 5.5 percent of all colon cancers, across a variety of ethnic groups. "These findings should put TGFBR1*6A on the map with better known cancer susceptibility genes such as BRCA1 and BRCA2 that have been implicated in an estimated 5 to 10 percent of all breast and ovarian cancers," said Dr. Pasche.

Altered genes trigger all cancer. "Most cases of breast, ovarian and colon cancers are caused by damage to the genes that builds up over a lifetime, but some people are born with a high risk of the disease," explains Pasche. "When inherited, the TGFRB1*6A gene makes people susceptible to having certain cells grow and divide uncontrollably, which may contribute to cancer development."

Northwestern's Cancer Genetics Program, which was launched last fall, is a comprehensive cancer genetics program that provides cancer predictive gene testing and genetic counseling. TGFBR1*6A testing is currently only offered at Northwestern as part of a research protocol at the Cancer Genetics Program, but Dr. Pasche predicts that testing for this gene will enter the mainstream of genetic testing in the near future. "The results of this study will certainly spark interest in genetic testing and counseling for TGFBR1*6A," he says.

"By spotting a mutated gene in an individual, we can sometimes detect cancer years earlier through increased cancer screening. Through genetic counseling and genetic testing, we aim to reduce the incidence of cancer among individuals with increased risk," explains Taya Young, MS, a genetic counselor at the Northwestern Cancer Genetics Program. Currently, there are several options for people who find themselves at increased risk of breast, ovarian and colon cancers. These include preventive drug therapy, increased surveillance, lifestyle changes and preventive surgery. "Genetics is still a very new specialty, and we are just at the tip of the iceberg in discovering how we can maximize its full potential," says Dr. Pasche.

Virginia Kaklamani M.D., an oncologist at Northwestern Memorial Hospital and assistant professor of medicine at the Feinberg School of Medicine, is the first author of the study. She adds, "The testing of TGFBR1*6A is not ready for primetime yet. We still have to understand its role in relation with other genes that we commonly test for, such as BRCA1 and BRCA2.

However, in the foreseeable future, we may be able to identify high-risk women more precisely because of the TGFBR1*6A mutation and prevent many cases of breast and ovarian cancer."

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About Northwestern Memorial's Cancer Program

With the important affiliation of Northwestern Memorial Hospital (NMH), Northwestern Memorial Faculty Foundation (N***) and The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, NMH has established a national reputation as a leader in providing state-of-the-art, patient-focused and family-centered care. The NMH cancer program is ranked among the top 40 in the country for this specialty by U.S. News and World Report's Best Hospitals issue.

http://www.sciencedaily.com/releases/2003/08/030828071406.htm

If you read anything new about cancer, please share it with us. Thank you. Tatie

Tatie
Posts: 28
Joined: Aug 2003

Not All Colorectal Cancer Patients Suited for Chemotherapy

By Amanda Gardner, HealthDay

WEDNESDAY, July 16 (HealthDayNews) -- Individuals whose colorectal cancer shows a specific genetic characteristic may not benefit from chemotherapy, which is often standard practice after surgery.

The findings, from a study appearing in the July 17 issue of the New England Journal of Medicine, form part of a larger movement to fine-tune cancer treatment to the individual.

"What we're looking for are specific aspects of tumors and genetic markers to see if they may be more amenable to more chemotherapy regimens," says Dr. Michael Spencer, an assistant clinical professor of surgery at the University of Minnesota in Minneapolis.

Colorectal cancer is the second-leading cancer killer and the fourth most commonly diagnosed cancer in the United States. According to the U.S. National Cancer Institute, women and men are equally at risk.

Tumors are usually removed with surgery but some individuals, especially those whose cancer has spread, are also advised to receive chemotherapy.

"In patients with a certain stage of the disease, the chance of recurrence is 50 to 60 percent," says Dr. Manish A. Shah, an assistant attending physician and gastrointestinal oncology specialist at Memorial Sloan-Kettering Cancer Center in New York City. "Chemotherapy reduces the chance of recurrence."

Or so doctors thought.

First, some basic genetics will help illuminate the study findings. All normal cells have areas where sequences of DNA repeat themselves. In tumor cells, however, the length of the repeated sequence can be longer or shorter than those in healthy cells. These so-called "microsatellite" areas can signal a problem with the body's ability to repair mistakes in cells.

"Errors do happen, but the body has checks and balances," Shah explains. "A breakdown happens when an error isn't picked up or it's picked up but the body doesn't care. A repeat is just a marker that cells aren't that good at repairing DNA." Once one error occurs, more mistakes happen downstream from that.

Cells with many sections of abnormal repeats are said to have "high-frequency instability." Cells with just a few such areas have "low-frequency instability," while those that have no such abnormalities are considered "stable." Some 85 percent of colorectal cancers exhibit low-frequency instability or stability, while the remaining 15 percent display high-frequency instability.

The authors of this multi-center study, which was led by researchers at Mount Sinai Hospital in Toronto, wanted to see if microsatellite status could predict how a patient responded to chemotherapy. To this end, they analyzed specimens from 570 patients with colon cancer who had participated in previous studies of chemotherapy. All the individuals had been diagnosed with stage II or stage III colon cancer and had been randomized into groups either receiving fluorouracil-based chemotherapy after surgery or just surgery.

Of the total 570 tissue specimens, 95 (16.7 percent) exhibited high instability, 60 (10.5 percent) demonstrated low instability and 415 (72.8 percent) were stable.

Interestingly, the patients with high instability had a better five-year survival rate when they did not receive chemotherapy than the other patients in the analysis who did not receive chemotherapy. Chemotherapy after surgery improved overall survival among patients with stable tumors or tumors displaying low instability.

The finding was not exactly a surprise. "It's an idea that's been around for the last five years as something, but it was not demonstrated as clearly as in this study," Shah says.

No one knows for sure why the results turned out the way they did, but there are theories. One possibility is the errors in the very unstable cells eventually accumulate to the point where they kill off the cells, Shah postulates. "The chemotherapy could cause the DNA to be more aggressive," he adds.

The question for physicians is whether they should be routinely checking microsatellite status in colorectal cancer patients, something which is relatively easy to do. "We haven't been checking, and maybe we should check," Shah says.

For the time being, however, the study authors and others caution that therapies should not be changed until there is more confirmation of the findings.

Tatie
Posts: 28
Joined: Aug 2003

Colorectal Cancer Drug Gets Second Look

By Serena Gordon

A drug that's currently used to treat colorectal cancer after it has spread to other parts of the body may help make radiation more effective at destroying rectal cancer cells in earlier stages.

"Given in combination with radiation and other drugs, [the drug] oxaliplatin may be an effective way to treat Stage 3 rectal cancer patients," says Dr. A. William Blackstock, an associate professor of radiation oncology at Wake Forest University. Blackstock and colleagues at Wake Forest University Baptist Medical Center reported their findings on oxaliplatin July 12 at the American Association for Cancer Research annual meeting in Washington D.C.

Staging cancer is how doctors gauge the severity of a cancer. Stages range from zero to four, and the higher the number, the more serious the cancer and the more it has spread to other parts of the body. Cancer that has spread is called metastatic.

Oxaliplatin was approved by the U.S. Food and Drug Administration last year to be used in combination with two other drugs, fluorouracil and leucovorin, for the treatment of metastatic colorectal cancer.

Nearly 150,000 Americans are diagnosed with colorectal cancer every year, according to the American Cancer Society. These cancers will kill more than 55,000 people in the United States this year. Symptoms of colorectal cancer include a change in bowel habits, diarrhea, constipation, blood in the stools, narrower stools, bloating, a feeling of fullness, abdominal cramps, frequent gas pains, unexplained weight loss, chronic fatigue and vomiting.

Because of promising results in treating advanced colorectal cancer, Blackstock and his colleagues were asked to see if this combination of drugs would enhance the effects of radiation therapy in earlier stages of cancer.

Blackstock and his team tested the combination on Stage 3 rectal cancer cells in the laboratory and had promising results.

"It is a radiation potentiator," confirms Blackstock. And, he says, "it's less likely that cancer cells will become resistant to oxaliplatin," which is a problem with older medications.

"This is an interesting observation, but there are no clinical applications now," says Dr. Howard Hochster, an oncologist at New York University Medical Center. Additionally, he says, "This study was done on one particular cell line. The findings may be specific to that cell line."

Dr. Peter Kozuch, an attending physician in Hematology/Oncology at St. Luke's-Roosevelt Hospital Center in New York City, agrees there are no immediate clinical applications from these findings, but, he adds, "This study is attempting to further explain the synergistic relationship between oxaliplatin and radiation."

"These findings could potentially be applied to patients undergoing radiation therapy for rectal cancer," Kozuch says.

All three doctors say oxaliplatin appears to be an effective medication against cancer and is generally well tolerated by patients. However, it does have some neurological side effects, the most common being numbness or tingling in the hands and feet.

Kozuch says many people can sidestep this side effect by avoiding contact with cold air, cold objects or cold beverages after receiving treatment. Once the medication is stopped, he says, these symptoms should gradually go away.

http://health.yahoo.com/search/healthnews?lb=s&p=id%3A44677

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