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[암 검사] 대장암 혈액 검사법 (미국국립암연구소회지)

미국국립암연구소회지(Journal of the National Cancer Institute – Oxford Journals) 최신호에
혈청 속에서 대장암 세포가 분비하는 마이크로 RNA를 탐지하는 혈액검사를 통해
결장-직장암을 진단할 수 있는 새로운 검사법을 보고한 논문입니다.

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  • Oxford Journals
  • Medicine
  • JNCI J Natl Cancer Inst
  • Volume 105, Issue 12
  • Pp. 849-859.
    http://jnci.oxfordjournals.org/content/105/12/849.abstract

    Serum miR-21 as a Diagnostic and Prognostic Biomarker in Colorectal Cancer



    + Author Affiliations




    1. Affiliations of authors: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX (YT, MT, KH, CRB, AG); Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Graduate School of Medicine, Mie University, Mie, Japan (YT, KT, YI, MK); Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan (TN).


    1. Correspondence to:
      Ajay Goel, Baylor University Medical Center, 3500 Gaston Ave, Gastrointestinal Cancer Research Laboratory, Ste H-250, Dallas, TX 75246 (e-mail: ajay.goel@baylorhealth.edu) and C. Richard Boland (rickbo@baylorhalth.edu).


    • Received August 1, 2012.
    • Revision received November 21, 2012.
    • Accepted February 28, 2013.



  • Abstract



    Background The oncogenic microRNAs (miRNAs) miR-21 and miR-31 negatively regulate tumor-suppressor genes. Their potential as serum biomarkers has not been determined in human colorectal cancer (CRC).



    Methods To determine whether miR-21 and miR-31 are secretory miRNAs, we screened expression in medium from 2 CRC cell lines, which was followed by serum analysis from 12 CRC patients and 12 control subjects. We validated expression of candidate miRNAs in serum samples from an independent cohort of 186 CRC patients, 60 postoperative patients, 43 advanced adenoma patients, and 53 control subjects. We analyzed miR-21 expression in 166 matched primary CRC tissues to determine whether serum miRNAs reflect expression in CRC. Patient survival analyses were performed by Kaplan–Meier analyses and Cox regression models. All statistical tests were two-sided.



    Results Although miR-21 was secreted from CRC cell lines and upregulated in serum of CRC patients, no statistically significant differences were observed in serum miR-31 expression between CRC patients and control subjects. In the validation cohort, miR-21 levels were statistically significantly elevated in preoperative serum from patients with adenomas (P < .001) and CRCs (P < .001). Importantly, miR-21 expression dropped in postoperative serum from patients who underwent curative surgery (P < .001). Serum miR-21 levels robustly distinguished adenoma (area under the curve [AUC] = 0.813; 95% confidence interval [CI] = 0.691 to 0.910) and CRC (AUC = 0.919; 95% CI = 0.867 to 0.958) patients from control subjects. High miR-21 expression in serum and tissue was statistically significantly associated with tumor size, distant metastasis, and poor survival. Moreover, serum miR-21 was an independent prognostic marker for CRC (hazard ratio = 4.12; 95% CI = 1.10 to 15.4; P = .03).



    Conclusions Serum miR-21 is a promising biomarker for the early detection and prognosis of CRC.



    Tests to Detect Colorectal Cancer and Polyps



    http://www.cancer.gov/cancertopics/factsheet/detection/colorectal-screening

    Key Points



    • Colorectal cancer is a disease in which cells in the colon or rectum become abnormal and divide without control, forming a mass called a tumor.
    • The exact causes of colorectal cancer are not known. However, studies show that certain factors increase a person’s chance of developing colorectal cancer.
    • Health care providers may suggest one or more tests for colorectal cancer screening, including a fecal occult blood test (FOBT); sigmoidoscopy; regular, or standard, colonoscopy; virtual colonoscopy; or double contrast barium enema (DCBE).
    • People should talk with their health care provider about when to begin screening for colorectal cancer, what tests to have, the benefits and risks (potential harms) of each test, and how often to schedule appointments.
    • New methods, such as the genetic testing of stool samples, to screen for colorectal cancer are under study.





    1. What is colorectal cancer?



      Colorectal cancer is a disease in which cells in the colon or rectum become abnormal and divide without control, forming a mass called a tumor. (The colon and rectum are parts of the body’s digestive system, which takes up nutrients from food and water, and stores solid waste until it passes out of the body.)


      Colorectal cancer cells may also invade and destroy the tissue around them. In addition, they may break away from the tumor and spread to form new tumors in other parts of the body.


      Colorectal cancer is the third most common type of non-skin cancer in men (after prostate cancer and lung cancer) and in women (after breast cancer and lung cancer). It is the second leading cause of cancer death in the United States after lung cancer. Although the rate of new colorectal cancer cases and deaths is decreasing in this country, an estimated 141,210 new cases of colorectal cancer and 49,380 deaths from this disease are expected to occur in 2011 (1).





    2. Who is at risk of developing colorectal cancer?



      The exact causes of colorectal cancer are not known. However, studies have shown that certain factors are linked to an increased chance of developing this disease (2–11), including the following:




      • Age—Colorectal cancer is more likely to occur as people get older. Although this disease can occur at any age, most people who develop colorectal cancer are over age 50.



      • Polyps—Polyps are abnormal growths that protrude from the inner wall of the colon or rectum. They are relatively common in people over age 50. Most polyps are benign (noncancerous), but experts believe that the majority of colorectal cancers develop in polyps known as adenomas. Detecting and removing these growths may help prevent colorectal cancer. The procedure to remove polyps is called a polypectomy.


        Some individuals may be genetically predisposed to develop polyps. Familial adenomatous polyposis, or FAP, is a rare, inherited condition in which hundreds of polyps develop in the colon and rectum. Because individuals with this condition are extremely likely to develop colorectal cancer, they are often treated with surgery to remove the colon and rectum in an operation called a colectomy. Rectum-sparing surgery may also be an option. In addition, the Food and Drug Administration (FDA) has approved an anti-inflammatory drug, celecoxib, for the treatment of FAP. Doctors may prescribe this drug in combination with surveillance and surgery to manage FAP.



      • Personal history—A person who has already had colorectal cancer is at an increased risk of developing colorectal cancer a second time. Also, research studies have shown that some women with a history of ovarian, uterine, or breast cancer have a higher than average chance of developing colorectal cancer.



      • Family history—Close relatives (parents, siblings, or children) of a person who has had colorectal cancer are somewhat more likely to develop this type of cancer themselves, especially if the family member developed the cancer at a young age. If many family members have had colorectal cancer, the chances increase even more.



      • Ulcerative colitis or Crohn colitis—Ulcerative colitis is a condition that causes inflammation and sores (ulcers) in the lining of the colon. Crohn colitis (also called Crohn disease) causes chronic inflammation of the gastrointestinal tract, most often of the small intestine (the part of the digestive tract that is located between the stomach and the large intestine). People who have ulcerative colitis or Crohn colitis may be more likely to develop colorectal cancer than people who do not have these conditions.



      • Diet—Some evidence suggests that the development of colorectal cancer may be associated with high dietary consumption of red and processed meats and low consumption of whole grains, fruits, and vegetables. Researchers are exploring what role these and other dietary components play in the development of colorectal cancer.



      • Exercise—Some evidence suggests that a sedentary lifestyle may be associated with an increased risk of developing colorectal cancer. In contrast, people who exercise regularly may have a decreased risk of developing colorectal cancer. Also see the NCI fact sheet Physical Activity and Cancer.



      • Smoking—Increasing evidence from epidemiologic studies suggests that cigarette smoking, particularly long-term smoking, increases the risk of colorectal cancer.





    3. What is screening, and why is it important?



      Screening is checking for health problems before they cause symptoms. Colorectal cancer screening can detect cancer; polyps; nonpolypoid lesions, which are flat or slightly depressed areas of abnormal cell growth; and other conditions. Nonpolypoid lesions occur less often than polyps, but they can also develop into colorectal cancer (12).


      If colorectal cancer screening reveals a problem, diagnosis and treatment can occur promptly. In addition, finding and removing polyps or other areas of abnormal cell growth may be one of the most effective ways to prevent colorectal cancer development. Also, colorectal cancer is generally more treatable when it is found early, before it has had a chance to spread.





    4. What methods are used to screen people for colorectal cancer?



      Health care providers may suggest one or more of the following tests for colorectal cancer screening:



      • Fecal occult blood test (FOBT)—This test checks for hidden blood in fecal material (stool). Currently, two types of FOBT are available. One type, called guaiac FOBT, uses the chemical guaiac to detect heme in samples of stool. Heme is the iron-containing component of the blood protein hemoglobin. Usually, samples of stool from three different bowel movements are collected for guaiac FOBT. The other type of FOBT, called immunochemical (or immunohistochemical) FOBT, uses antibodies to detect human hemoglobin protein in samples of stool (13–15). Depending on the type of immunochemical FOBT, stool samples from one to three bowel movements are collected. Studies have shown that FOBT, when performed every 1 to 2 years in people ages 50 to 80, can help reduce the number of deaths due to colorectal cancer by 15 to 33 percent (13–15).
      • Sigmoidoscopy—In this test, the rectum and lower colon are examined using a lighted instrument called a sigmoidoscope. During sigmoidoscopy, precancerous and cancerous growths in the rectum and lower colon can be found and either removed or biopsied. Studies suggest that regular screening with sigmoidoscopy after age 50 can help reduce the number of deaths from colorectal cancer (14). A thorough cleansing of the lower colon is necessary for this test.
      • Colonoscopy—In this test, the rectum and entire colon are examined using a lighted instrument called a colonoscope. During colonoscopy, precancerous and cancerous growths throughout the colon can be found and either removed or biopsied, including growths in the upper part of the colon, where they would be missed by sigmoidoscopy. However, it is not yet known for certain whether colonoscopy can help reduce the number of deaths from colorectal cancer. A thorough cleansing of the colon is necessary before this test, and most patients receive some form of sedation.
      • Virtual colonoscopy (also called computerized tomographic colonography)—In this test, special x-ray equipment is used to produce pictures of the colon and rectum. A computer then assembles these pictures into detailed images that can show polyps and other abnormalities. Because it is less invasive than standard colonoscopy and sedation is not needed, virtual colonoscopy may cause less discomfort and take less time to perform. As with standard colonoscopy, a thorough cleansing of the colon is necessary before this test. Whether virtual colonoscopy can reduce the number of deaths from colorectal cancer is not yet known.
      • Double contrast barium enema (DCBE)—In this test, a series of x-rays of the entire colon and rectum are taken after the patient is given an enema with a barium solution and air is introduced into the colon. The barium and air help to outline the colon and rectum on the x-rays. Research shows that DCBE may miss small polyps. It detects about 30 to 50 percent of the cancers that can be found with standard colonoscopy (14).

      In addition, doctors often perform a digital rectal exam (DRE) during routine physical examinations and may use this test to check for abnormal areas in the lower part of the rectum. They may also perform a single-specimen guaiac FOBT on stool collected during a DRE, but research has shown that this approach is not very accurate and cannot be recommended as the only method of screening for colorectal cancer (16).


      Scientists are still studying colorectal cancer screening methods, both alone and in combination, to determine how effective they are. Studies are also under way to clarify the potential risks, or harms, of each screening test. Question 5 includes a list that outlines some of the advantages and disadvantages, including potential harms, of specific colorectal cancer screening tests.





    5. How can people and their health care providers decide which colorectal cancer screening test(s) to use and how often to be screened?



      Several major organizations, including the U.S. Preventive Services Task Force (a group of experts convened by the U.S. Public Health Service), the American Cancer Society, and professional societies, have developed guidelines for colorectal cancer screening. Although some details of their recommendations vary regarding which screening tests to use and how often to be screened, all of these organizations support screening for colorectal cancer.


      People should talk with their health care provider about when to begin screening for colorectal cancer, what tests to have, the benefits and harms of each test, and how often to schedule appointments.


      The decision to have a certain test will take into account several factors, including the following:



      • The person’s age, medical history, family history, and general health
      • The accuracy of the test
      • The potential harms of the test
      • The preparation required for the test
      • Whether sedation is necessary during the test
      • The follow-up care after the test
      • The convenience of the test
      • The cost of the test and the availability of insurance coverage

      The following list outlines some of the advantages and disadvantages, including potential harms, of the colorectal cancer screening tests described in this fact sheet.


      Fecal Occult Blood Test (FOBT)
      Advantages:

      • No cleansing of the colon is necessary.
      • Samples can be collected at home.
      • Cost is low compared with other colorectal cancer screening tests.
      • Does not cause bleeding or tearing/perforation of the lining of the colon.
      Disadvantages:

      • Fails to detect most polyps and some cancers (13, 15).
      • False-positive results (the test suggests an abnormality when none is present) are possible (13, 15).
      • Dietary restrictions may be needed before the test.
      • Additional procedures, such as colonoscopy, may be needed if FOBT indicates an abnormality.

      Sigmoidoscopy
      Advantages:

      • Test is usually quick, with few complications.
      • For most patients, discomfort is minimal.
      • In some cases, the doctor may be able to perform a biopsy and remove polyps during the test, if necessary.
      • Less extensive cleansing of the colon is necessary for this test than for a colonoscopy.
      Disadvantages:

      • Any polyps in the upper part of the colon will be missed because the test allows the doctor to view only the rectum and the lower part of the colon.
      • Very small risk of bleeding or tearing/perforation of the lining of the colon (17).
      • Additional procedures, such as colonoscopy, may be needed if the test indicates an abnormality.

      Colonoscopy
      Advantages:

      • Allows the doctor to view the rectum and the entire colon.
      • Doctor can perform a biopsy and remove polyps or other abnormal tissue during the test, if necessary.
      Disadvantages:

      • May not detect all small polyps, nonpolypoid lesions, and cancers, but is one of the most sensitive tests currently available.
      • Thorough cleansing of the colon is necessary before this test.
      • Some form of sedation is used in most cases.
      • Although uncommon, complications such as bleeding and/or tearing/perforation of the lining of the colon can occur (17).

      Virtual Colonoscopy
      Advantages:

      • Allows the doctor to view the rectum and the entire colon.
      • No risk of bleeding or tearing/perforation of the lining of the colon.
      Disadvantages:

      • May not detect all small polyps, nonpolypoid lesions, and cancers (18, 19).
      • Thorough cleansing of the colon is necessary before the test.
      • If a polyp or nonpolypoid lesion 6 to 9 millimeters in size or larger is detected, standard colonoscopy, usually immediately after the virtual procedure, will be recommended to remove the polyp or lesion or perform a biopsy (20, 21).

      Double-Contrast Barium Enema (DCBE)
      Advantages:

      • Usually allows the doctor to view the rectum and the entire colon.
      • Complications are rare.
      • No sedation is needed.
      Disadvantages:

      • May not detect some small polyps and cancers (14).
      • Thorough cleansing of the colon is necessary before the test.
      • False-positive results are possible.
      • Doctor cannot perform a biopsy or remove polyps during the test.
      • Additional procedures are necessary if the test indicates an abnormality.




    6. Do insurance companies pay for colorectal cancer screening?



      People should check with their health insurance provider to determine their colorectal cancer screening benefits. Because virtual colonoscopy is a fairly new procedure, reimbursement policies may be more uncertain than for other types of screening. Medicare covers several colorectal cancer screening tests for its beneficiaries. Specific information about Medicare benefits is available on the Medicare website.





    7. What happens if a colorectal cancer screening test shows an abnormality?



      If a screening test finds an abnormality, the health care provider will perform a physical exam and evaluate the person’s personal and family medical history. Additional tests may be ordered. These tests may include x-rays of the gastrointestinal tract, sigmoidoscopy, or, most often, colonoscopy (see Question 4). The health care provider may also order a blood test called a CEA assay to measure carcinoembryonic antigen, a protein that is sometimes detected in greater amounts in patients with colorectal cancer. If an abnormality is found during a sigmoidoscopy, a biopsy or polypectomy may be performed during the test, and a colonoscopy may be recommended. If an abnormality is found during a standard colonoscopy, a biopsy or polypectomy is performed to determine whether cancer is present. If an abnormality is detected during virtual colonoscopy, most patients would be referred for a standard colonoscopy the same day.





    8. Are new tests under study for colorectal cancer screening?



      Genetic testing of stool samples is being studied as a possible way to screen for colorectal cancer (15, 22, 23). The lining of the colon is constantly shedding cells into the stool. Testing stool samples for genetic alterations that occur in colorectal cancer cells may help doctors find evidence of cancer or precancerous growths. Research conducted thus far has shown that this kind of test can detect colorectal cancer in people already diagnosed with this disease by other means. However, more studies are needed to determine whether this type of test can accurately detect colorectal cancer or precancerous polyps in people who do not have symptoms.


      Information about ongoing clinical trials that are studying methods for colorectal cancer screening can be found in NCI’s clinical trials database. You may also contact NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237) or by e-mail for assistance with searching the clinical trials database or for other cancer information needs.




    Selected References


    1. American Cancer Society (2011). Cancer Facts and Figures 2011 Exit Disclaimer. Atlanta, GA: American Cancer Society. Retrieved December 19, 2011.
    2. Hill LB, O’Connell JB, Ko CY. Colorectal cancer: epidemiology and health services research. Surgical Oncology Clinics of North America 2006; 15(1):21–37. [PubMed Abstract]
    3. Schatzkin A, Mouw T, Park Y, et al. Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study. The American Journal of Clinical Nutrition 2007; 85(5):1353–1360. [PubMed Abstract]
    4. Koushik A, Hunter DJ, Spiegelman D, et al. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies. Journal of the National Cancer Institute 2007; 99(19):1471–1483. [PubMed Abstract]
    5. Gonzalez CA. The European prospective investigation into cancer and nutrition (EPIC). Public Health Nutrition 2006; 9(1A):124–126. [PubMed Abstract]
    6. Norat T, Bingham S, Ferrari P, et al. Meat, fish, and colorectal cancer risk: the European prospective investigation into cancer and nutrition. Journal of the National Cancer Institute 2005; 97(12):906–916. [PubMed Abstract]
    7. Howard RA, Freedman DM, Park Y, et al. Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study. Cancer Causes and Control 2008; 19(9):939–953. [PubMed Abstract]
    8. Friedenreich C, Norat T, Steindorf K, et al. Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition. Cancer Epidemiology, Biomarkers and Prevention 2006; 15(12):2398–2407. [PubMed Abstract]
    9. Samad AK, Taylor RS, Marshall T, Chapman MA. A meta-analysis of the association of physical activity with reduced risk of colorectal cancer. Colorectal Disease 2005; 7(3):204–213. [PubMed Abstract]
    10. Paskett ED, Reeves KW, Rohan TE, et al. Association between cigarette smoking and colorectal cancer in the Women’s Health Initiative. Journal of the National Cancer Institute 2007; 99(22):1729–1735. [PubMed Abstract]
    11. Chao A, Thun MJ, et al. Cigarette smoking and colorectal cancer mortality in the cancer prevention study II. Journal of the National Cancer Institute 2000; 92(23):1888–1896. [PubMed Abstract]
    12. Soetikno RM, Kaltenbach T, Rouse RV, et al. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. Journal of the American Medical Association 2008; 299(9):1027–1035. [PubMed Abstract]
    13. Burch JA, Soares-Weiser K, St John DJ, et al. Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review. Journal of Medical Screening 2007; 14(3):132–137. [PubMed Abstract]
    14. PDQ® Cancer Information Summary. National Cancer Institute; Bethesda, Maryland. Colorectal Cancer Screening—Health Professional. Date last modified: 09/30/2011. Accessed 12/19/2011.
    15. Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE. Noninvasive testing for colorectal cancer: a review. American Journal of Gastroenterology 2005; 100(6):1393–1403. [PubMed Abstract]
    16. Collins JF, Lieberman DA, Durbin TE, Weiss DG, Veterans Affairs Cooperative Study #380 Group. Accuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice. Annals of Internal Medicine 2005; 142(2):81–85. [PubMed Abstract]
    17. Gatto NM, Frucht H, Sundararajan V, et al. Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study. Journal of the National Cancer Institute 2003; 95(3):230–236. [PubMed Abstract]
    18. Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. New England Journal of Medicine 2003; 349(23):2191–2200.  [PubMed Abstract]
    19. Johnson CD, Chen MH, Toledano AY, et al. Accuracy of CT colonography for detection of large adenomas and cancers. New England Journal of Medicine 2008; 359(12):1207–1217. [PubMed Abstract]
    20. Rex DK, ACG Board of Trustees. American College of Gastroenterology action plan for colorectal cancer prevention. American Journal of Gastroenterology 2004; 99(4):574–577. [PubMed Abstract]
    21. Summerton S, Little E, Cappell MS. CT colonography: current status and future promise. Gastroenterology Clinics of North America 2008; 37(1):161–189. [PubMed Abstract]
    22. Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. New England Journal of Medicine 2004; 351(26):2704–2714. [PubMed Abstract]
    23. Itzkowitz SH, Jandorf L, Brand R, et al. Improved fecal DNA test for colorectal cancer screening. Clinical Gastroenterology and Hepatology 2007; 5(1):111–117. [PubMed Abstract]
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