October 6, 2008, 10:14 PM CT

Stool DNA testing for colorectal cancer

The first generation of a stool DNA test to identify early colorectal cancer has limitations, as per a Mayo Clinic-led study reported in the Oct. 7, 2008, issue of Annals of Internal Medicine Results did not corroborate findings of an earlier multicenter study that showed stool DNA testing was more accurate than fecal blood testing for colorectal cancer detection. *.

"But the concerns we identified with stool DNA testing are all solvable," says David Ahlquist, M.D., lead researcher in the study that included 4,482 participants and 22 academic medical centers. Scientists have hoped that stool DNA testing could be the user-friendly and accurate screening tool that would increase screening numbers.

More than half of adults in the United States have never been screened for colorectal cancer, the second-leading cause of cancer deaths. While available screening tools work, the most effective tests involve time, effort and costs. For example, colonoscopy requires fasting, bowel cleansing, a doctor visit, sedation, an invasive procedure and lost work time -- factors that contribute to low screening participation.

This blinded study, conducted from 2001 to 2007, compared screening effectiveness of two widely used fecal blood tests (Hemoccult and HemoccultSensa) with a stool DNA test in average-risk patients, ages 50 to 80. The DNA test used was the prototype for PreGenPlus, the first commercially-used stool DNA test, and waccording toformed on samples sent to EXACT Sciences in Marlborough, Mass. All participants underwent a colonoscopy, the gold standard in current screening. Scientists used colonoscopy as the benchmark to detect cancer or premalignant polyps......... Posted by: Sue      Read more         Source

October 3, 2008, 5:09 AM CT

Colonoscopy reduces colorectal cancer

Patients who undergo a complete negative colonoscopy have a reduced occurence rate of colorectal cancer, confirms a study published in Clinical Gastroenterology and Hepatology However, in the proximal colon, the incidence reduction of colorectal cancer following complete negative colonoscopy differs in magnitude and timing. The reduction of colorectal cancer is observed in about half of the 14 follow-up years and for the most part occurs after just seven years of follow-up. Clinical Gastroenterology and Hepatology is the official journal of the American Gastroenterological Association (AGA) Institute.

"Our study raises a question about the effectiveness of colonoscopy in usual clinical practice," said Linda Rabeneck, MD, MPH, of the University of Toronto and Institute for Clinical Evaluative Sciences in Toronto and lead author of the study. "Our findings suggest that the effectiveness of colonoscopy is reduced for cancers arising in the proximal colon. Whether this is due to colonoscopy quality, or whether it is due to tumor biology is the key issue that we need to address."



Findings

The relative rate of colorectal cancer overall and the relative rate of distal (left-sided) colorectal cancer in the study group remained significantly lower than the control population. The relative rate of proximal (right-sided) colorectal cancer was significantly lower than the control population in half of the follow-up years, mainly after seven years of follow-up......... Posted by: Sue      Read more         Source

October 1, 2008, 8:25 PM CT

Breakthrough optical technology to assess colon cancer risk

Scientists at NorthShore University HealthSystem (NorthShore) and Northwestern University have discovered that fiber optic technology can for the very first time effectively measure blood levels in the colonic lining (mucosa) in humans, thus having potential applications for analyzing risk of colon cancer.

The study appears in the October 2008 issue of Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

The study used fiber optic technology to map microvascular blood content in patients during colonoscopy. The results provide the first indication that the early increase in blood supply (EIBS) is detectable in humans and that a high blood level mirrors proximity to neoplasia (process of tumor formation). The findings also suggest that this technology could be a valuable screening tool for enhancing polyp detection and could lead to improvements in colon cancer prevention.

"Our premise is that since the lining of the large intestine -- rectum and colon -- is contiguous, if you see an abnormality in one part of the colon, then somewhere else in the colon you have a higher likelihood of harboring an adenoma [non-malignant tumor] or carcinoma [cancerous tumor]," said Hemant K. Roy, M.D., director of gastroenterology research at NorthShore University HealthSystem and the study's principal clinical researcher. "EIBS strengthens our premise thanks largely to the unique and accurate ability of Four Dimensional Elastic Light Scattering Fingerprinting (4D-ELF)"......... Posted by: Sue      Read more         Source

September 14, 2008, 10:09 PM CT

Cancer-causing gene in many colon cancers

Demonstrating that despite the large number of cancer-causing genes already identified, a number of more remain to be found, researchers at Dana-Farber Cancer Institute have linked a previously unsuspected gene, CDK8, to colon cancer.

The discovery of CDK8's role in cancer was made possible by new tools for assessing the activity of specific genes, say the authors of the new study. As these tools are further improved, the stream of newly discovered cancer genes is expected to increase, providing new avenues for treatment, the authors suggest. The findings are being published as an advanced online publication by the journal Nature on Sept. 14.

"This study provides confirmation that a number of of the genes involved in cancer have yet to be identified," remarked the study's senior author, William Hahn, MD, PhD, of Dana-Farber and the Broad Institute of Harvard and M.I.T. "When it comes to identifying gene targets for treatment, we've really only scratched the surface".

The study is noteworthy in another respect, as well, the authors indicated. A number of of the abnormal proteins associated with cancer are known as "transcription factors" because they're able to "read" cell DNA and use that information for producing other cell proteins. Eventhough transcription factors are important regulators, this class of proteins has proven to be impossible to target with drugs. Genes that influence such transcription factors, however, make attractive targets for drugs, since they can potentially disrupt the cancer process and disable tumor cells. CDK8 is such a gene......... Posted by: Sue      Read more         Source

September 9, 2008, 9:29 PM CT

Early stage colon cancer and gatekeeper gene

The absence or inactivation of the RUNX3 gatekeeper gene paves the way for the growth and development of colon cancer, Singapore researchers report in the Sept. issue of the journal Cancer Cell Prior studies have shown that RUNX3 plays a role in gastric, breast, lung and bladder cancers.

The inactivation of RUNX3 occurs at a very early stage of colon cancer, as per the Singapore scientists' studies with human tissue samples and animal models.

Because the inactivation of RUNX3 is relatively easy to detect, and it is possible that inactivated RUNX3 can be reactivated, this new research may prove to be a crucial step in the development of an early diagnostic test as well as a therapeutic target for colon cancer.

Previous to these new findings, researchers knew that a tumor suppressor gene called APC is disrupted in most cases of human colon cancer. APC disruption activates bete-catenin and TCF4, a protein complex that plays an important role in cancer development. For decades, this has been considered the molecular basis for colon cancer.

These latest findings are the first to show that the activity of beta- catenin/TCF4 also is inhibited by RUNX3.

The Singapore researchers are based at the National University of Singapore's (NUS) Yong Loo Lin School of Medicine and the Institute of Molecular and Cell Biology (IMCB), one of the 14 research institutes under the country's Agency for Science, Technology and Research (A*STAR)......... Posted by: Sue      Read more         Source

September 2, 2008, 8:04 PM CT

Colorectal cancer screening should start at age 50

Colorectal adenomas, the precursor polyps in virtually all colorectal cancers, occur infrequently in younger adults, but the rate sharply increases after age 50. Additionally, African Americans have a higher rate of proximal, or right-sided, polyps, and may have a worse prognosis for survival if the polyps become malignant. Therefore, the results of this study further emphasize the importance of colonoscopies, which view the entire colon, for the prevention of colorectal cancer beginning at age 50. The results of this study, which represents the largest investigation, by several-fold, of this kind, were published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute.

"While colorectal polyps are rare in adults aged 30 to 50, our study reveals an increase in polyp prevalence with age and a dramatic increase in colorectal adenoma incidence occurring in adults over the age of 50," said Francis M. Giardiello, MD, of The John Hopkins University and lead author of the study. "Understanding the natural occurrence of colorectal polyps, particularly in younger adults, is important to the development of colorectal cancer prevention strategies".



Findings

Scientists found the prevalence of colorectal polyps in younger adults increased from 1.72 percent to 3.59 percent from age 30 to 50. This rate sharply increased after age 50 with the prevalence of polyps ranging from 10.1 to 12.06 percent in the sixth and ninth decade, respectively. The study results quantified the number of adenomas typically found in people under the age of 50. It is important to note that those with two or more adenomas under 50 years of age represent unusual individuals who might merit closer colonoscopic surveillance for subsequent adenoma development......... Posted by: Sue      Read more         Source

July 14, 2008, 9:48 PM CT

Colorectal cancer screening rates still too low

Eventhough colorectal cancer screening tests are proven to reduce colorectal cancer mortality, only about half of U.S. men and women 50 and older receive the recommended tests, as per a report in the July 2008 issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

The Centers for Disease Control and Prevention conducted a National Health Interview Survey and found only 50 percent of men and women 50 and older had received screening in 2005. Eventhough this was an improvement over the 43 percent of screened individuals reported in 2000, it is still far from optimal, researchers say.

"Colorectal cancer is one of the leading cancer killers in the United States, behind only lung cancer. Screening has been shown to significantly reduce mortality from colorectal cancer, but a lot of people are not yet getting screened," said Jean A. Shapiro, Ph.D., an epidemiologist at the Centers for Disease Control and Prevention (CDC).

Shapiro says a major problem appears to be insurance coverage. Among people without health insurance, scientists found the rate of colorectal cancer screening was 24.1 percent in comparison to over 50 percent of insured Americans, depending on the type of insurance. Among patients without a usual source of health care, the screening rate was 24.7 percent in comparison to 51.9 percent of patients with a usual source of health care......... Posted by: Sue      Read more         Source

May 21, 2008, 9:53 PM CT

Virtual biopsy for colon polyp

A probe so sensitive that it can tell whether or not a cell living within the human body is veering towards cancer development may revolutionize how future colonoscopies are done, say scientists from the Mayo Clinic in Jacksonville, Fla.

Investigators have observed that technology known as a high resolution confocal endomicroscopy probe system can determine whether a colon polyp is non-malignant (not premalignant) - without having to remove it for examination by a pathologist.

Their study, to be presented at the Digestive Disease Week, a scientific meeting of gastrointestinal specialists and scientists held in San Diego, shows that using the probe system was 89 percent accurate in identifying whether polyps were either premalignant or benign. But more importantly, it was correct 98 percent of the time in flagging polyps that were benign, which would then not need to be removed for biopsy. The Mayo researchers, who are the first in the U.S. to comprehensively test the system in the colon, believe they can push accuracy close to 100 percent with more research.

What this means is that the probe system can be used to during a colonoscopy to rule out removal of polyps that are not harmful, says the study's senior author, Michael Wallace, M.D., M.P.H., Professor of Medicine at Mayo Clinic......... Posted by: Sue      Read more         Source

May 18, 2008, 9:48 PM CT

Which patients should get treatment for colorectal cancer

A new study being presented at the American Society of Clinical Oncology meeting in Chicago (Abstract #4020), may change therapy practice in about 25 percent of colon cancer patients and is the basis for proposed changes to the way colorectal cancers will be staged.

This new study, using National Cancer Institute (NCI) SEER population-based statistic registries from 1992 to 2004, and phase III clinical trial data, shows that outcomes of patients with positive nodes (Stage III) in colorectal cancer interact, to a greater extent than previously thought, with how deeply the cancer penetrates the bowel wall.

Survival outcomes depend on the thickness of the primary cancer within or beyond the bowel wall in addition to whether nodes are positive or negative. A patient with a node positive thin lesion (i.e., confined to the bowel wall) has a stage III cancer with better survival outcomes than a patient with a Stage II node negative thick cancer that penetrates beyond the bowel wall. The current standard of practice for patients with colon cancer is that all or most Stage III patients receive chemotherapy after surgical removal of their cancer, but Stage II patients do not routinely receive chemotherapy. In a separate National Cancer Data Base (NCDB) analysis, patients with Stage III colon cancers confined to the bowel wall who did not receive chemotherapy still had better survival than Stage II patients......... Posted by: Sue      Read more         Source

April 17, 2008, 7:41 PM CT

Inherited colon cancer mutation is widespread

A gene mutation responsible for the most common form of inherited colon cancer is older and more common than formerly believed, as per a recent study.

The findings provide a better understanding of the spread and prevalence of the American Founder Mutation, a common cause in North America of Lynch syndrome, a hereditary cancer syndrome that greatly increases a persons risk for developing cancers of the colon, uterus and ovaries.

The same researchers discovered the mutation in 2003. That research identified nine families with the mutation and concluded that a German immigrant couple brought the mutation to North America in 1727.

The latest study includes an additional 32 families and indicates that the mutation is actually about 500 years old, suggesting that it arose several generations earlier in Europeans or perhaps in Native Americans.

Of the 41 families overall, most are clustered in Kentucky, Ohio and Texas.

Researchers at the Ohio State University Comprehensive Cancer Center and Creighton University conducted the study, published recently in the journal Cancer Research.

The increased age of the American Founder Mutation means that it is significantly more prevalent in the United States than previously thought, says principal investigator Albert de la Chapelle, a researcher with Ohio States Human Cancer Genetics program......... Posted by: Sue      Read more         Source

April 13, 2008, 8:53 PM CT

Smoking related to subset of colorectal cancers

Smoking puts older women at significant risk for loss of DNA repair proteins that are critical for defending against development of some colorectal cancers, as per research from a team led by Mayo Clinic scientists.

In a study being presented at the annual meeting of the American Association for Cancer Research (AACR), the scientists observed that women who smoked were at increased risk for developing colorectal tumors that lacked some or all of four proteins, known as DNA mismatch repair (MMR) proteins. These proteins keep cells lining the colon and rectum healthy because they recognize and repair genetic damage as well as mistakes that occur during cell division.

Scientists think that, in this study population, few if any of the four proteins were absent because of an inherited genetic alteration. We believe that smoking induces a condition within intestinal cells that does not allow MMR genes to express their associated proteins, and this loss leads to formation of tumors in some women, says the studys lead author, Mayo gastroenterologist Paul Limburg, M.D.

The scientists also discovered a direct association between the number of cigarettes smoked daily by study participants and increased risk of developing these specific tumors. They say a number of prior studies have observed only a very weak positive association between use of cigarettes and development of the cancer......... Posted by: Sue      Read more         Source

April 3, 2008, 9:50 PM CT

Colon Cancer's Potential for Metastasis

Some colon cancers are destined to spread to the liver and other parts of the body, whereas others are successfully treated by surgical removal of the tumor. Now, Howard Hughes Medical Institute researchers have observed that the ability of a colon tumor to metastasize arises early in its development.

Those colon cancers that spread carry the ability to metastasize from the time they become malignant, the scientists found. They don't need to acquire any new genetic mutations to become metastatic. The research also suggests that once a colon carcinoma develops, if it is going to spread outside the colon, it will do so in less than two years.

"The ability to metastasize is hard-wired into this group of tumors in the colon," said Sanford Markowitz, a Howard Hughes Medical Institute investigator at Case Western Reserve University. "It isn't something that happens after a cancer cell wanders off and leaves the colon."

Markowitz and colleagues published their findings in the Proceedings of the National Academy of Sciences on March 3, 2008.

Colon cancer is the second leading cause of cancer mortality in the United States, causing about 60,000 deaths annually. But there are a number of more cases of colon cancer that are cured by surgical removal of the tumor. Markowitz and his team wanted to understand the genetic differences between the two types......... Posted by: Sue      Read more         Source

March 9, 2008, 4:57 PM CT

New colorectal cancer gene

Case Western Reserve University School of Medicine scientists published a study in the March 7th issue of The American Journal of Human Genetics identifying the hereditary components of colorectal cancer (CRC.) Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study is the first large linkage study of families with CRC and colon polyps in the country. Because only five percent of CRC cases are due to known gene defects, this NIH-funded study is designed to identify the remaining CRC-related susceptibility genes. The team built on a prior study which identified a specific region on chromosome 9q that harbors a CRC susceptibility gene. Upon review of a whole genome scan of all chromosome pairs in 194 families, the scientists were able to identify additional CRC gene regions on chromosomes 1p, 15q, and 17p.

While the overall Case Western Reserve University School of Medicine study looked at families with colon cancer and colon polyps, the study also analyzed families with different clusters of cancer, such as CRC with multiple polyps and CRC with breast cancer. These different phenotypes appeared to link to different chromosomal regions, which the study teams says supports the idea of multiple susceptibility genes causing different types of cancers. These links will be further investigated in the next phase of the study......... Posted by: Sue      Read more         Source

March 5, 2008, 8:51 PM CT

Tests that prevent colorectal cancer

New consensus colorectal cancer guidelines released recently state for the first time that the primary goal of colorectal cancer screening is cancer prevention. Prior guidelines have given equal weight to tests for detecting cancer and preventing cancer. By removing polyps from the large bowel, colonoscopy is the only screening test that also prevents colorectal cancer.

Colorectal cancer prevention should be the primary goal of screening, said Nicholas LaRusso, MD, AGAF, president, American Gastroenterological Association (AGA) Institute. Detection and removal of premalignant lesions is essential to improve the health of Americans.

The guidelines, which represent the most current scientific evidence and expert opinion available, are a joint effort of the American Cancer Society, the American College of Radiology and the U.S. Multi-society Task Force (comprised of the American College of Gastroenterology, the American Gastroenterological Association (AGA) Institute and the American Society for Gastrointestinal Endoscopy).

While the AGA Institute considers optical colonoscopy the definitive screening and therapy procedure for colorectal cancer, we support all clinically proven options for colorectal cancer screening. There are a number of tests available for screening and everyone age 50+ should talk with their doctor about what test is available to them, said John I. Allen, MD, MBA, AGAF chair of the AGA Institute Clinical Practice and Quality Management Committee......... Posted by: Sue      Read more         Source

February 24, 2008, 9:36 PM CT

5-fluorouracil in colonic neoplasm?

5-fluorouracil (5-FU) is a common chemotherapeutical drug. It exerts its antitumor effect through competitive thymidylate synthase (TS) inhibition. Thymidylate synthase (TS) catalyses deoxyuridine-5-monophosphate (dUMP) to 2-deoxythymydine-5-monophosphate (dTMP). It is the only de novo source of thymidylate, an essential precursor of DNA biosynthesis. In the 5-untranslated region of TS gene, there a unique tandem repeated sequence. There are three predominant genotypes of TS: (1) Homozygous with two tandem repeats (2R/2R); (2) homozygous with three tandem repeats (3R/3R); (3) heterozygous with both alleles (2R/3R). It was reported that TS genes with the triple repeats have higher expression activity than those with double repeats in vitro and in vivo.

The critical role of TS in nucleotide metabolism has made it an important target for cancer chemotherapy. Intratumoral TS protein expression before the chemoradiation therapy has been observed to inversely correlate with the response to 5-FU chemotherapy. Patients with low TS levels have better clinical outcome than those with high TS levels. Detecting the intratumoral TS levels is important for patients who are going to receive 5-FU-based chemotherapy, as these can be used to forecast the efficacy of chemotherapy. However, the classical assay for TS-activity determination (high-performance liquid chromatography with output monitored by radioactive flow detector) is tedious and expensive. A simple way to detect the TS levels is necessary. A research article would be published on January 28, 2008 in the World Journal of Gastroenterology addresses this question......... Posted by: Sue      Read more         Source

February 20, 2008, 8:04 AM CT

Cancer deaths down but

New data revealing decreasing trends in cancer deaths in the United States overall, and in colorectal cancer deaths in particular, highlight the remarkable benefits of colorectal cancer screening tests, but the lifesaving potential of these tests is unrealized for a number of Americans as per experts from the American College of Gastroenterology. Racial minorities, uninsured Americans and even Medicare patients who should be tested are not being screening appropriately, and other recent studies reveal that they are diagnosed with more advanced cancers in comparison to patients with private insurance.

Today, the American Cancer Society reported a downward trend in cancer deaths between 2004 and 2005. Deaths from cancer of the colon and rectum decreased from 1998 to 2004 among both men and women, as per ACS. The report attributes early detection to this sharp decline in colon cancer deaths. Early detection of colorectal cancer, when it is most treatable, directly results in improved survival, exceeding 90 percent when detected at the earliest stage.

As per ACG President Amy E. Foxx-Orenstein, D.O., FACG, The good news is that colorectal cancer deaths are down, but marked differences in the experience of colorectal cancer, its impact on quality of life, and death rates are seen between whites and blacks, and between the uninsured, and even those with health coverage under Medicare and Medicaid. As per Dr. Foxx-Orenstein, The American College of Gastroenterology is committed to national policy changes to improve access to colorectal screening and increased use of these proven prevention strategies, including reversing Medicares massive cuts to reimbursement for these tests since the benefit was first introduced, as well as to payments in ambulatory surgery centers where a number of screening tests are performed......... Posted by: Sue      Read more         Source

February 13, 2008, 9:22 PM CT

Earlier colon cancer screening for smokers

New evidence suggests screening for colorectal cancer, which is now recommended to begin at age 50 for most people, should start five to 10 years earlier for individuals with a significant lifetime exposure to tobacco smoke, a University of Rochester Medical Center study said.

An examination of 3,450 cases observed that current smokers were diagnosed with colon cancer approximately seven years earlier than people who never smoked. The study is also one of the first to link exposure to second-hand smoke, particularly early in life, with a younger age for colon cancer onset.

The article appears online in the Journal of Cancer Research and Clinical Oncology.

The message for physicians and patients is clear: When making decisions about colon cancer screening you should take into account smoking history as well as family history of disease and age, said lead author Luke J. Peppone, Ph.D., research assistant professor of Radiation Oncology at the James P. Wilmot Cancer Center at the University of Rochester.

Peppones group examined data from patients diagnosed with colorectal cancer between 1957 and 1997 at Roswell Park Cancer Institute in Buffalo. (Peppone joined the University of Rochester in 2007, coming from RPCI. Co-authors are from RPCI.)......... Posted by: Sue      Read more         Source

December 18, 2007, 8:43 PM CT

Colon cancer screenings may not pay off

Even though current guidelines advocate colorectal cancer screenings for those with severe illnesses, they may bring little benefit and may actually pose harm, as per a recent study by Yale School of Medicine scientists reported in the Archives of Internal Medicine.

The study offers a new approach for assessing who is likely to benefit from a screening so that screening recommendations can be tailored more effectively to individual patients.

First author R. Scott Braithwaite, M.D., and colleagues developed a new method of evaluating medical screening tests like colonoscopy, called the payoff time, which is the minimum amount of time it takes for the benefits from a test to exceed its harms (i.e., its complications and side effects). The method can also be applied to patients of any age and illness.

To estimate the payoff time for using colonoscopy to screen for colorectal cancer, the team focused on two patient groups that included 50-year-old men with HIV, and 60-year-old women with congestive heart failure.

Braithwaite said the payoff time for colorectal cancer screening was as long as five years for 50-year-old men and as long as 2.9 years for 60-year-old women. Because patients with severe congestive heart failure have a life expectancy of less than 2.9 years, they were more likely to be harmed than benefited by colorectal cancer screening, say the researchers, whereas patients with HIV have a life expectancy of greater than five years, so they were likely to benefit from colorectal cancer screening......... Posted by: Sue      Read more         Source

December 17, 2007, 9:30 PM CT

Underuse of colorectal cancer screening

Two recently released studies confirm an alarming reality, that a majority of Americans who should be getting screened for colorectal cancer are not. Men and women over the age of 50 should be screened for colorectal cancer, but as per a research studyin the journal Cancer, scientists observed that among an assessment of Medicare beneficiaries between 1998 and 2004, only 25.4 percent of people were screened, despite Medicare coverage for colorectal cancer screening. As per figures released by the Agency for Healthcare Research and Quality, only half of all Americans age 50 and over have had a screening colonoscopy.

These numbers are very discouraging and, unfortunately they confirm prior studies that show not enough people are getting screened for colorectal cancer. This disease is preventable and treatable when caught in its early stages, and screening is a covered benefit for those eligible for Medicare, said Grace Elta, MD, president of the American Society for Gastrointestinal Endoscopy (ASGE). We know that screening works. As per a recent study by leading cancer groups, including the American Cancer Society and the CDC, deaths from colorectal cancer dropped nearly 5 percent between 2002 and 2004. Prevention through screening and the removal of premalignant polyps were among the reasons credited for the decline. The ASGE encourages all people age 50 and older to talk to their doctor about getting screened for colorectal cancer......... Posted by: Sue      Read more         Source