Gene variant that increases colon cancer risk identified - Northwestern's cancer genetics program

Main Category: Cancer / Oncology
Article Date: 03 May 2005 - 0:00 PDT

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A paper published in this week's Journal of Clinical Oncology says Transforming Growth Factor Beta Receptor 1*6A (TGFBR1*6A) - a mutated gene present in nearly one in eight people and the most commonly inherited cancer susceptibility gene identified so far - might be responsible for a significant proportion of familial colorectal cancers. The study, published by researchers at Northwestern Memorial Hospital and Northwestern University's Robert H. Lurie Comprehensive Cancer Center, says 15 to 20 percent of all colorectal cancers are familial, but only 7-8 percent are caused by mutations of known colorectal cancer genes such as the APC, MLH1, MSH2 and MSH6 genes.

In an earlier study, Dr. Pasche and his colleagues had found that TGFBR1*6A may increase the risk for all colon cancers by 20 percent. "There is growing evidence that TGFBR1*6A is associated with an increased risk of colorectal cancer but its specific contribution to familial colorectal cancer was unknown," explained Dr. Pasche. Now, Dr. Pasche believes the gene is especially potent as a cause for familial colon cancers.

The study looked at 208 patients with colorectal cancer and a strong family history of colorectal cancer and found that the number of TGFBR1*6A carriers was twice as high among patients without a mutation in the colorectal cancer genes MLH1, MSH2 and MSH6 as compared with patients without a mutation in these genes. The number of carriers of two copies of the TGFBR1*6A gene was 13-fold higher than in the general population, suggesting that TGFBR1*6A homozygosity (possessing two identical forms of a particular gene, one inherited from each parent) is associated with a particularly high risk of colorectal cancer.

Colorectal cancers are the second leading cause of cancer death among adult Americans and familial colorectal cancer is a major public health problem because it causes a relatively large percentage of these cancers. "We wanted to identify the genes responsible for the remaining unexplained familial colorectal cancers," says Dr. Pasche. "That is a first step toward better prevention and treatment of those cancers."

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."

About the Robert H. Lurie Comprehensive Cancer Center

The Robert H. Lurie Comprehensive Cancer Center of Northwestern University is the only cancer center in Illinois and one of only 39 in the nation to hold the "comprehensive" designation by the National Cancer Institute (NCI). This designation reflects the Cancer Center's commitment to the highest standards of cancer research, patient care, cancer prevention, education and community outreach. In addition, the Cancer Center is a founding member of the National Comprehensive Cancer Network (NCCN), an exclusive alliance of 19 of the world's leading cancer centers. The Cancer Center receives more than $90 million in extramural funding for cancer-relevant research each year and treats more than 5,000 new patients each year who have access to cutting-edge treatment and clinical trials.

About Northwestern Memorial Hospital

Northwestern Memorial Hospital is one of the country's premier academic medical centers and is the primary teaching hospital of Northwestern University's Feinberg School of Medicine. Northwestern Memorial and its Prentice Women's Hospital and Stone Institute of Psychiatry have 744 beds and more than 1,200 affiliated physicians and 5,000 employees. Providing state-of-the-art care, Northwestern Memorial is recognized for its outstanding clinical and surgical advancements in such areas as cardiothoracic and vascular care, gastroenterology, neurology and neurosurgery, oncology, organ and bone marrow transplantation, and women's health.

Northwestern Memorial received the prestigious 2005 National Quality Health Care Award and is listed in eight specialties in this year's US News & World Report's issue of "America's Best Hospitals." The hospital is also cited as one of the "100 Best Companies for Working Mothers" by Working Mother magazine for the past 5 years and has been chosen by Chicagoans for a decade as their "most preferred hospital" in National Research Corporation's annual survey.

Contact: Amanda Widtfeldt
awidtfel@nmh.org
312-926-2955
Northwestern Memorial Hospital
http://www.nmh.org