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ARRA Investments in Colorectal Cancer

Public Health Burden
Colorectal cancer (CRC) is the third most common cancer in both men and women in the United States and the second leading cause of cancer death. In 2009, it is estimated that more than 145,000 new cases of CRC will be diagnosed and there will be nearly 50,000 deaths from this disease. CRC incidence and death rates are higher for African American men and women than for men and women of other racial and ethnic groups.

Although no definitive method of preventing CRC has been identified, clinical trials have shown that regular use of certain drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), may reduce the risk of CRC among those at high risk for the disease. ARRA-funded research is exploring additional approaches to preventing this disease, such as:
  • Determining whether a compound called 5-aminosalicylic acid, which is related to the NSAID aspirin and is used to treat patients with ulcerative colitis, can prevent CRC in these patients, who have a higher risk of CRC.1
A number of techniques to screen for CRC have been developed, including fecal occult blood testing (FOBT), sigmoidoscopy, colonoscopy, and computed tomographic colonography (virtual colonoscopy, or VC, a noninvasive method of creating images of the colon).  Although regular screening for people over 50 years of age is commonly recommended, many people do not get regular screening. ARRA-funded research is examining new approaches to both screening and encouraging individuals to get screened, including the following:
  • Creating a colonoscopy registry to identify factors that are associated with improved effectiveness and efficiency of this CRC screening method.2
  • Investigating whether infrastructure changes at a large HMO could increase the proportion of patients who undergo screening for CRC.3
  • Developing a more accurate computer-aided detection system to improve the ability of VC to identify polyps and cancers.4
  • Comparing patient adherence to different CRC screening tests (FOBT, sigmoidoscopy, colonoscopy, and VC) scheduled by their primary care provider to identify the most cost-effective strategy to decrease mortality from CRC. Barriers to screening will be identified to help inform future programs to increase CRC screening adherence.5
Surgery is the most common treatment for CRC, and it may cure disease that has not yet spread to other parts of the body. Many CRC patients receive chemotherapy or radiation therapy before or after surgery. Several targeted therapies, including the monoclonal antibody bevacizumab, which inhibits the growth of blood vessels to tumors, have been approved for the treatment of advanced CRC. Nevertheless, patients with CRC that has spread—especially if it has spread to distant sites in the body—have poor survival rates. ARRA-funded research is investigating new ways to improve CRC outcomes, including the following:
  • Identifying genetic variations that influence responsiveness to bevacizumab and developing an algorithm on the basis of this information that will allow patients with advanced CRC who are likely to benefit from the addition of bevacizumab to chemotherapy to be distinguished from those who are not likely to benefit from added bevacizumab.6
  • Discovering specific microRNAs that clinicians can use as biomarkers to identify patients who have tumors that are resistant to standard chemotherapy drugs used to treat CRC and who, therefore, are candidates for alternative or experimental treatments.7
Genomic Research
Research into the genetics of cancer, whether the disease is an inherited form or one that develops in the absence of a family history, will help identify molecular markers that can be used to assess risk and prognosis and to define targets for new therapies. The genetics of CRC are being studied in several ARRA-funded projects. For example:
  • Genome-wide scans involving more than 5000 CRC patients and 11,000 control subjects will be conducted to identify potential CRC susceptibility genes. The effects of environmental factors, including smoking, medications, alcohol, physical activity, and diet on CRC risk in relation to identified susceptibility genes will be assessed.8
Comparative Effectiveness Research
A variety of genomic and molecular tests have been developed to help diagnose particular cancers, make assessments of prognosis, and guide treatment choices. However, little is known about the comparative effectiveness of these tests. ARRA-funded research will investigate this question in the context of CRC. For example:
  • Several genetic tests related to colon cancer that may help doctors understand who will develop the disease and what therapies specific patients should receive will be evaluated; the researchers will also determine who gets tested, how test results help people decide what to do, and whether patients have different health outcomes when they get tested.9
Health Disparities
In addition to racial and ethnic variations in the rates of CRC incidence and death, there is wide variation in these rates among U.S. states, with the rates generally being higher in Southern and Midwestern states. ARRA-funded research is attempting to understand and address these health disparities.  For example:
  • An Appalachian Community Cancer Network (ACCN) will be developed by building on the foundation of the Appalachia Cancer Network Special Populations Network. A pilot project of the ACCN will focus on the primary and secondary prevention of CRC.10

  1. 3R01CA124693-02S1 -- Chemoprevention of colitis-associated neoplasia by 5-ASA -- Clapper, Margie L (PA)
  2. 3R01CA131141-02S1 -- Variations in colonoscopy screening: a population based study -- Dietrich, Allan J (NH)
  3. 3R01CA121125-03S1¬ -- Systems of support (SOS) to increase colon cancer screening and follow-up -- Green, Beverly B (WA)
  4. 3R01CA131718-01A1S1 -- NA-MIC virtual colonoscopy -- Yoshida, Hiroyuki (MA)
  5. 3R01CA106773-04S1 -- Adherence and the economics of colon cancer screening -- Inadomi, John M (CA)
  6. 1R01CA139003-01A1 -- Interaction of anti-angiogenic and cytotoxic therapies in colorectal cancer -- O’Dwyer, Peter J (PA)
  7. 1DP2OD006506-01 -- The discovery of microRNAs that predict chemotherapeutic responsiveness of cancer -- Tavazoie, Sohail F (NY)
  8. 3R01CA059045-12S1 -- Genome-wide association study of nonsynonymous SNPs in colon cancer -- Peters, Ulrike (WA)
  9. 1RC2CA148471-01 -- Comparative effectiveness in genomic & personalized medicine for colorectal cancer -- Goddard, Katrina A (CA)
  10. 3U01CA114622-05S3 -- Appalachia Community Cancer Network -- Dignan, Mark B (KY)

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