Stool DNA Testing Could Play Expanded Role in Colon Cancer Prevention

(BUSINESS WIRE)--Research teams led by Mayo Clinic have demonstrated for the first time that two types of colorectal pre-cancers can be detected through noninvasive stool DNA testing. The two studies being presented demonstrate that stool DNA testing may be useful for detection of premalignant dysplasia in patients with inflammatory bowel disease (IBD) and of an important type of colorectal pre-cancer called serrated polyps. The findings were presented at Digestive Disease Week 2010, the annual meeting of the American Gastroenterological Association.

“This was significantly higher than the 7 percent rate with conventional fecal blood tests.”

David Ahlquist, M.D., a gastroenterologist with Mayo Clinic and the senior investigator, said that sensitive stool DNA test methods developed at Mayo Clinic can detect common forerunners of colorectal cancer. “Detection of precursor lesions during screening is essential if cancer prevention is the goal,” Dr. Ahlquist says.

Compared to widely used fecal blood tests, stool DNA testing has higher detection rates for curable stage colorectal cancer and for common precancerous polyps (called adenomas).

Detection of Colorectal Precancerous Lesions in Inflammatory Bowel Disease

The first study, presented on May 3 at Digestive Disease Week, involves identifying both cancer and a precancerous lesion, called dysplasia, in people who suffer from IBD. In a blinded study with 10 cases and 10 controls done in conjunction with Mount Sinai Medical Center and the University of Chicago, researchers found that stool DNA testing was positive in nine out of 10 cases (five of five with cancer, and four of five with dysplasia).

“This study shows that cancer and pre-cancer in IBD can be detected noninvasively,” says Dr. Ahlquist. “The 90 percent detection rate by stool DNA testing is remarkable. It’s important for people with IBD because they are at much higher risk for colorectal cancer than the general population. Given the limitations of colonoscopies in detecting these lesions, stool DNA testing could play a complementary role to improve the effectiveness of cancer surveillance.”

Detection of Serrated Colorectal Polyps

The second study, presented on May 4, involves detecting serrated colorectal polyps. Unlike common adenomas, which usually protrude from the colon lining and are easy to see, serrated polyps are typically flat and the same color as the colon lining. Dr. Ahlquist says serrated polyps have been ignored or excluded from most screening studies to date because it wasn’t clear they were associated with cancer. “Now they are regarded as the forerunner in roughly 30 percent of colon cancers,” says Dr. Ahlquist. “Most of these are located on the right side of the colon, where screening has had less impact historically.”

For this study, researchers first took tissue and identified two genetic markers that were present in serrated polyps but not in normal colon. The team assayed the markers (mutant BRAF and methylated vimentin genes) in stool samples from 14 cases and 19 control patients who had undergone screening colonoscopies. In blinded fashion, they compared results to fecal blood tests on the same specimens.

“We observed a 71 percent detection rate with stool DNA testing,” says Dr. Ahlquist. “This was significantly higher than the 7 percent rate with conventional fecal blood tests.”

“Detection of these important types of precancer by stool DNA testing offers promise in our efforts to more effectively and affordably prevent colorectal cancer,” says Dr. Ahlquist. “However, findings from both pilot studies need to be corroborated in larger studies.”

Collaboration

The studies were funded by the National Institutes of Health and the Charles Oswald Foundation. Mayo Clinic co-authors for the colorectal neoplasia and inflammatory bowel disease study include John Kisiel, M.D.; Tracy Yab; Fareeda Hussain, William Taylor; Jonathan Harrington; Mary Devens; Julie Simonson; Megan Garrity-Park; William Sandborn, M.D.; Edward Loftus, M.D; and Hongzhi Zou, M.D., PhD. Co-authors for the serrated colorectal polyps study include Hussain, Yab, Harrington, Taylor, Thomas Smyrk, M.D.; Douglas Mahoney; and Dr. Zou.

Disclosure

Drs. D. Ahlquist and D. Zou, Mses. T. Yab and F. Hussain; and Messrs. Taylor and Harrington and Mayo Clinic have a financial interest related to technology used with this research. This technology has been licensed to Exact Sciences. Mayo Clinic stands to receive royalties from the licensing of this technology and holds an equity position in Exact Sciences.

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Older Women with Diabetes Face Higher Risk for Colon Cancer

(BUSINESS WIRE)--A research team led by Mayo Clinic physicians has found that older women with diabetes face a more than doubled risk for some types of colorectal cancer. The findings are being presented at Digestive Disease Week 2010, the annual meeting of the American Gastroenterological Association.

Colorectal cancer (http://www.mayoclinic.org/colon-cancer/) remains the third-leading cause of cancer deaths among women in the United States. Diabetes has been identified as a colon cancer risk factor, but the mechanisms aren’t completely understood. For this population-based cohort study, researchers examined data from 37,695 participants of the Iowa Women’s Health Study (IWHS), which enrolled women ages 55–69 in 1986 and remains ongoing. Of these women, 2,361 reported a diagnosis of Type 2 diabetes and 1,200 developed colorectal cancer.

To find the links between colorectal cancer and diabetes, the researchers worked with regional pathology laboratories to obtain tumor tissue samples from IWHS participants who were diagnosed with colorectal cancer. They linked the tissue samples with other IWHS data, looking for cancer pathways and risk factors, and whether those risk factors were associated with three different molecular markers: microsatellite instability (MSI), CpG island methylation (CIMP), and BRAF gene mutations.

“Diabetes was more strongly associated with the MSI-high, CIMP-positive and BRAF-mutation cancer subtypes in this group of older women,” says Mayo Clinic gastroenterologist Paul Limburg, M.D. (http://www.mayoclinic.org/bio/10658084.htm). Dr. Limburg explains that diabetes appeared to confer a greater than twofold increase in risk for these molecularly-defined tumors, compared to women without diabetes.

“Knowing that diabetic women have these findings should help to facilitate more appropriate colorectal cancer prevention and treatment options,” says Anthony Razzak, M.D., a Mayo Clinic research fellow and presenter at the conference. “Our findings may lead to new strategies for colon cancer screening, chemotherapy and chemoprevention in women with diabetes.”

“From a research perspective, this information allows us to clarify how environmental exposures and other risk factors might effect tumor formation at a molecular level,” says Dr. Razzak. For future projects, the researchers will work to understand more about the biology of colorectal cancer and how it is influenced by diabetes, as well as other chronic conditions and exposures. They hope to use that information to improve patient care.

“Unfortunately, diabetes and colon cancer are both very common in the United States, so making links between these disorders has substantial public health implications,” says Dr. Limburg.

Mayo Clinic’s Division of Gastroenterology and Hepatology (http://www.mayoclinic.org/gi-rst) has been ranked No. 1 in the U.S. News & World Report Honor Roll of Top Hospitals since the rankings began 20 years ago.

Collaboration

The study was funded by the National Cancer Institute. Additional Mayo Clinic co-authors are Amy Oxtenko, M.D.; Robert Vierkant; Lori Tillmans; Alice Wang; Susan Slager, Ph.D; Thomas Smyrk, M.D.; Stephen Thibodeau, Ph.D.; and James Cerhan, M.D., Ph.D. Co-authors from other institutions are Daniel Weisenberger, Ph.D., and Peter Laird, Ph.D., both of the University of Southern California Epigenome Center; Charles Lynch, M.D., Ph.D., University of Iowa College of Public Health, Iowa City; Kristin Anderson, Ph.D., and Lisa Harnack, Ph.D., both of the University of Minnesota Cancer Center, Minneapolis; Robert Haile, Ph.D., of the University of Southern California School of Medicine, Los Angeles; and John Potter, M.D., Fred Hutchinson Cancer Research Center, Seattle.

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CDC Awards $22 Million for Colorectal Cancer Screening Program

The Centers for Disease Control and Prevention (CDC) has awarded a total of $22 million to 26 states and tribal organizations to provide colorectal cancer screening services for low-income people aged 50-64 years, who are underinsured or uninsured. Colorectal cancer is the second leading cause of cancer deaths among men and women aged 50 and older in the United States.

The awards range from $358,283 to $1.1 million. The awardees are expected to begin screening patients for colorectal cancer within six months.

The states receiving five-year awards are: Alabama, Arizona, California, Colorado, Connecticut, Delaware, Florida, Iowa, Maine, Maryland, Massachusetts, Minnesota, Montana, Nebraska, New Hampshire, New Mexico, New York, Oregon, Pennsylvania, South Dakota, Utah, and Washington. The tribal organizations receiving awards are: Alaska Native Tribal Health Consortium, Arctic Slope Native Association, South Puget Intertribal Planning Agency, and Southcentral Foundation.

The funding will support screening and diagnostic follow-up care, data collection and tracking, public education and outreach, provider education, and an evaluation to measure the clinical outcomes, costs, and effectiveness of the program. The awardees can choose from among any of the recommended screenings for colorectal cancer - colonoscopy, sigmoidoscopy and stool testing.

"Colorectal cancer kills more people than any other cancer except lung cancer," said CDC Director Thomas Frieden, M.D., M.P.H. "These colorectal cancer screening awards will save lives. We need to reach more adults aged 50 and over and others at high risk to prevent colorectal cancer."

In 2005, more than 141,000 new cases of colorectal cancer were diagnosed and 53,000 people died from this disease. The number of new colorectal cancer cases could be reduced by as much as 90 percent if all precancerous polyps (abnormal growths in the colon or rectum), were identified using screening tests and removed before they become cancerous. However, only half of all U.S. adults aged 50 or older have been screened appropriately for colorectal cancer, and while screening rates are slowly increasing, disparities still exist. Screening rates remain higher for whites compared to all other races, for non-Hispanics compared to Hispanics, and for people with health insurance compared to those with no health insurance.

"Screening tests can detect colorectal cancer at its earliest stages, when it is most treatable," said Laura Seeff, M.D., medical director of CDC's colorectal cancer screening program. "This screening program has tremendous potential to address the disparities that exist in colorectal cancer screening and to save lives."

The goals of CDC's colorectal cancer screening program are to increase population-level screening among all persons aged 50 and older in the participating states and tribes, and to reduce health disparities in colorectal cancer screening, incidence and mortality.
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FDA Clears Test that Helps Identify Type of Cancer in Tumor Sample

The U.S. Food and Drug Administration has cleared for marketing a test that can help health care professionals determine what type of cancer cells are present in a malignant tumor.

The Pathwork Tissue of Origin test compares the genetic material of a patient’s tumor with genetic information on malignant tumor types stored in a database.

It uses a microarray technology to analyze thousands of pieces of genetic material at one time. The test considers 15 common malignant tumor types, including bladder, breast, and colorectal tumors.

"The clearance of the Pathwork test is another step in the continued integration of molecular-based medicine into standard practice," said Daniel Schultz, M.D., director of the FDA's Center for Devices and Radiological Health, which oversees medical diagnostics. "In the past, scientists have classified different types of cancers based on the organs in which the tumors develop. With the help of microarray technology, they will be able to classify these types of cancers in a standardized non-reader dependent manner based on the patterns of gene activity in the tumor cells."

The Pathwork Tissue of Origin test is the second in vitro diagnostic multivariate index assay (IVDMIA) device to be cleared by the FDA. In July 2007, the FDA issued a draft guidance document to address premarket pathways and postmarket requirements for IVDMIAs. IVDMIA tests combine the values of multiple variables to yield a single, patient-specific result.

Nearly every cell of the body contains a full set of chromosomes and identical genes but only a fraction of these genes are turned on or expressed in any given cell. Gene expression occurs when certain molecular information contained within DNA is transcribed to create molecules known as RNA. These molecules in turn make the proteins that perform most of the critical functions of cells.

Microarray technology can simultaneously measure gene expression levels of large numbers of genes. Small DNA fragments are placed or arrayed on a slide and then RNA, which has been extracted from the tumor tissue and labeled with a fluorescent marker, is spread over this "microarray."

Since RNA binds to its complementary DNA strand, how much binding occurs indicates how active the gene being evaluated is. This can be determined by putting the array under a scanning microscope and measuring the intensity of the fluorescent light at each point on the array.

Pathwork’s proprietary software converts the scanned image data to gene expression measurements. The gene expression patterns are compared with known gene expression patterns in the database that correspond to different tumor types.

The Pathwork Tissue of Origin test has been found to provide patterns that confirm existing tissue of origin of the 15 common tumor types using standard clinical and pathological information. This accuracy of this test is similar to that achieved by expert pathologists using current standards of practice.

PathChip, the gene expression array used in the Pathwork Tissue of Origin test, is custom-designed for Pathwork Diagnostics of Sunnyvale, Calif., by Affymetrix Inc., of Santa Clara, Calif. PathChip is the first custom Affymetrix gene expression array to be cleared for diagnostic use.

New Study Shows Colorectal Cancer Screening Rates Increasing Among U.S. Adults - Disparities in screening still persist in certain populations

The percentage of U.S. adults aged 50 years and older getting screened
for colorectal cancer is increasing according to a study released by the
Centers for Disease Control and Prevention's (CDC) Morbidity and
Mortality Weekly Report. The study uses state-level Behavioral Risk
Factor Surveillance Survey (BRFSS) data that have been combined to
estimate that 60.8 percent of adults were current with colorectal cancer
screening recommendations in 2006, compared with 53.9 percent in 2002.

"While we are encouraged to see an increase in colorectal cancer
screening rates, certain groups are still not getting screened as
recommended," said Djenaba A. Joseph, M.D., the report's lead author
and medical officer, Division of Cancer Prevention and Control. "We
need to ensure that all adults have access to these life-saving tests
because there is strong scientific evidence that screening can prevent
colorectal cancer deaths."

Screening prevalence was lower among all racial and ethnic minorities
studied compared to whites. The study also reports that screening rates
continue to be lower among those without health insurance, with low
income, and with less than a high school education.

Colorectal cancer is the nation's second leading cause of cancer deaths.
In 2004, almost 145,000 people in the United States were diagnosed with
colon cancer and more than 53,000 died from the disease.

Regular screening is recommended for men and women beginning at age 50,
using one or a combination of these screening tests:

* Home Fecal occult blood test (FOBT) - a test that checks for
hidden blood in the stool.
* Colonoscopy - an examination of the rectum and entire colon
using a colonscope (a lighted instrument).
* Flexible sigmoidoscopy - an examination of the rectum and lower
colon using a sigmoidoscope (a lighted instrument).
* Double contrast barium enema - a series of x-rays of the entire
colon and rectum.

Screening tests for colorectal cancer can find precancerous polyps
(abnormal growths) in the colon and rectum before they turn into cancer.
Screening also helps find this cancer at an early stage when treatment
can be most effective.

To estimate the current rates of colorectal cancer screening and to
measure changes in use of screening, CDC scientists compared data from
the 2002, 2004, and 2006 BRFSS telephone surveys. For this report,
sigmoidoscopy and/or colonoscopy are described as lower endoscopy.

Significant findings from this study show:

* The percentage of adults aged 50 years and older who reported
having had a home FOBT within one year and/or lower endoscopy within 10
years before the survey increased from 54 percent in 2002, 57 percent in
2004, and to 60 percent in 2006.

* The percentage of adults who reported having had a home FOBT
within one year before the survey declined from 22 percent in 2002, 19
percent to 2004, and to 16 percent in 2006.

* The percentage of adults who reported having had lower endoscopy
within 10 years before the survey increased from 45 percent in 2002, to
50 percent in 2004, and to 56 percent in 2006.

* The percentage of adults who reported never being screened for
colorectal cancer decreased from 34 percent in 2004, 32 percent in 2004,
and to 30 percent in 2006.

* In 2006, the percentage of adults who reported having had a home
FOBT and/or lower endoscopy within 10 years before the survey ranged
from 52 percent in Mississippi to 71 percent in Connecticut.

To address the disparities in screening, in 2005, CDC established
colorectal cancer screening demonstration programs at five sites in the
United States for persons with low income and inadequate or no
colorectal cancer screening insurance coverage. Additional information
about these programs is available at
http://www.cdc.gov/cancer/colorectal/what_cdc_is_doing/demonstration/.

CDC's Screen for Life: National Colorectal Cancer Action Campaign is
aimed at informing men and women aged 50 years or older about the
importance of having regular colorectal cancer screening tests.
Information about Screen for Life can be found at
http://www.cdc.gov/cancer/colorectal/sfl/.

Speak with your doctor or health care professional about getting
screened for colorectal cancer, using one or more of the recommended
screening tests.