The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, or PLCO, is a large-scale clinical trial to determine whether certain cancer screening tests reduce death from cancer. The PLCO is testing the effectiveness of early prostate, lung, colorectal, and ovarian cancer detection using the following tests: Digital rectal examination and blood prostate-specific antigen (PSA) testing for prostate cancer; chest X-ray for lung cancer; flexible sigmoidoscopy for colorectal cancer; and transvaginal ultrasound and the blood cancer antigen, CA-125, for ovarian cancer. Screening for cancer may enable doctors to discover and successfully treat the disease earlier, thus preventing deaths. Numerous epidemiologic and other studies are also part of this research.

Sponsored and run by the National Cancer Institute's (NCI) Division of Cancer Prevention, the PLCO trial is taking place at 10 screening centers across the United States: Birmingham, Ala.; Denver, Colo.; Washington, D.C.; Honolulu, Hawaii; Detroit, Mich.; Minneapolis, Minn.; St. Louis, Mo.; Pittsburgh, Pa.; Salt Lake City, Utah; and Marshfield, Wis.

Between 1993, when the trial opened, and 2001, when enrollment was completed, a total of 154,942 women and men between the ages of 55 and 74 joined PLCO. Screening of participants will continue until 2006. Additional follow-up will continue for at least 10 more years to determine the benefits or harms of the cancer screening exams being studied.

The PLCO trial also includes research on the genetic and environmental causes of cancer (prostate, lung, colorectal, ovarian, and other types of cancer) and studies of new methods for the early detection of cancer, in collaboration with the NCI's Division of Cancer Epidemiology and Genetics.

Together, prostate, lung, colorectal, and ovarian cancers account for 42 percent of all diagnosed cancers in the United States and nearly half of all cancer deaths (47 percent). An estimated 266,360 people will die of prostate, lung, colorectal, and ovarian cancer in this country in 2005.

Background on Colorectal Cancer

Colorectal cancer is the third most commonly diagnosed cancer among both men and women in the United States. Family history of the disease and a personal history of inflammatory bowel disease or polyps are factors known to increase a person's risk of colorectal cancer. A diet high in fat and low in dietary fiber also may increase a person's risk.

The colon and rectum are the lowest portion of the digestive system. The colon is the last five or six feet of the intestine and the rectum is the last eight to ten inches of the colon. Because the areas are connected, cancer researchers often report this as a single type of cancer.

In the PLCO trial, researchers are testing flexible sigmoidoscopy. During a sigmoidoscopy, a thin, lighted viewing instrument is inserted into the rectum to examine the left, or distal, portion of the colorectum. PLCO subjects with a polyp or mass noted on sigmoidoscopy are often referred for further examination with colonoscopy, a procedure that examines the entire colorectum.

Patient Population, Trial Design, and Data Collection

The PLCO is a randomized, controlled trial in which 154,942 persons ages 55 to 74 at entry are randomly assigned to two study arms: Half to undergo cancer screening (intervention group) and half to continue their normal health care routine (control group). Both groups answer yearly questionnaires about their health and give biologic samples (blood and tissue) for studies of cancer causes and of early markers for cancer (biomarkers).

The sigmoidoscopy exam is offered twice—at the initial visit and at either the third or fifth annual visit, depending when the participant enrolled in PLCO. With the completion of enrollment and screening, researchers continue to follow participants in both groups for at least 13 years from the time they enrolled.

Results/Publications

The following PLCO analyses regarding colorectal cancer have been published, with the most recent studies listed first:

Screening and Related Clinical Studies

• The PLCO trial offers a unique opportunity to examine the effectiveness of screening flexible sigmoidoscopy in a large, diverse population. Results from the initial screening and 12 months of follow-up were comparable to other studies.

Of 77,465 subjects randomized to the screening arm, 64,658 (83 percent) received the baseline flexible sigmoidoscopy exam. A total of 18 percent of women and 28 percent of men were found to have a positive screen (i.e., a lesion or mass reported). The detection rate of colorectal cancer in subjects undergoing screening was 1.8 per 1,000 in women and 3.8 per 1,000 in men, while the detection rate for advanced adenomas (pre-cancerous polyps) was 23 per 1,000 in women and 43 per 1,000 in men. Because of the large size of the study population, the broad geographic representation, and the follow-up criteria, the results of the PLCO trial will offer a benchmark for screening flexible sigmoidoscopy in the United States.

Reference: Weissfeld JL, Schoen RE, et al. "Flexible Sigmoidoscopy in the PLCO Cancer Screening Trial: Results from the Baseline Screening Examination of a Randomized Trial." Journal of the National Cancer Institute. Vol. 97, No. 13. July 6, 2005.

• Repeat screening flexible sigmoidoscopy three years after a negative exam will detect abnormalities or masses in the lower portion of the colon.

The PLCO trial is evaluating the effect of flexible sigmoidoscopy (FSG) on colorectal cancer mortality. The trial screened the intervention group upon entry to the study and then in three years. Individuals included in this analysis had an initial FSG that showed no abnormalities or masses and then underwent a screening FSG three years later.

Of the 11,583 individuals without an abnormality or mass on initial FSG, 9,317 (80.4 percent) returned for repeat screening after three years. Of the people who returned, 1,292 (13.9 percent) had a polyp or mass detected. Of those with a polyp or mass, 951 (73.6 percent) went on to have follow-up screening, colonoscopy or repeat FSG. In the distal colon, 292 (3.1 percent) were found to have an adenoma (a pre-cancerous polyp) and 78 (0.8 percent) were found to have either an advanced adenoma or cancer.

Reference: Schoen RL, Pinsky PF, et al. "Results of Repeat Sigmoidoscopy 3 Years After a Negative Examination." Journal of the American Medical Association. Vol. 290, No. 1. July 2, 2003.

• Data from the second screening for participants in the PLCO trial determined that excellent adherence to repeat screening with flexible sigmoidoscopy could be achieved. However, gender may impact adherence to repeat screening, with women less likely to return for follow-up screening.

This study was comprised of 10,164 patients from the PLCO screening trial who had a negative/normal initial screen. These patients were scheduled for repeat flexible sigmoidoscopy three years after the initial screening. Almost 87 percent of eligible patients returned for repeat screening.

Measures of nonadherence with repeat sigmoidoscopy varied significantly according to gender. Compared with men, women missed the year-three clinic almost two times more often than men, and women who attended the year-three clinic refused repeat sigmoidoscopy more than two times more often than men.

Reference: Weissfeld JL, Ling BS, et al. "Adherence to Repeat Screening Flexible Sigmoidoscopy in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial." Cancer. Vol. 94. 2002.

• Overall, patients' thoughts are similar and positive for both CT colonography (virtual colonoscopy) and traditional colonoscopy, with less favorable thoughts about bowel preparation. Most patients state that they would prefer virtual colonoscopy for future evaluation.

A newer examination for detection of colorectal abnormalities is CT colonography, or "virtual colonoscopy." Computer-simulated three-dimensional images are used to examine the mucosal surface of the colon and a two-dimensional view is used to visualize the structure of the colon. This non-invasive alternative offers several advantages to the patient over colonoscopy: No need for sedation or monitoring of vital signs and no recovery period. Disadvantages are that the conventional bowel preparation program is still needed and that the insufflation (blowing gas into the colon to enlarge the area) is uncomfortable.

A total of 120 patients were recruited for this study. The patients who were included had an increased risk of colorectal abnormalities due to suspected polyps, rectal bleeding, blood in the stool, history of prior polyps, or a family or personal history of colorectal cancer. These patients received virtual colonoscopy followed by a traditional colonoscopy on the same day.

The study showed that for both virtual colonoscopy and traditional colonoscopy, patients' thoughts after the procedure were more favorable than what was expected. Patients expressed more favorable thoughts about colonoscopy for pain and embarrassment with most responses being "none" to "a little" for both exams. Overall appraisals of the tests were favorable and similar between colonoscopy and virtual colonoscopy. Patients mainly expressed "not unpleasant" to "a little unpleasant." Overall appraisal of the bowel preparation was the most negative.

Reference: Ristvedt SL, McFarland EG, et al. "Patient Preferences for CT Colonography, Conventional Colonoscopy, and Bowel Preparation." The American Journal of Gastroenterology. Vol. 98, No. 3. 2003.

• Subjects who have undergone screening flexible sigmoidoscopy (FSG) and were found to have non-advanced adenomas (pre-cancerous polyps) in the lower portion of the colon have a similar risk for advanced abnormalities in the upper portion of the colon as subjects with no adenomas in the lower colon. Subjects with advanced adenomas in the lower colon, however, are at an increased risk. Patients found to have these abnormalities were referred for a colonoscopy to examine the upper portion of the colon.

Sigmoidoscopy is used to view the lower (distal) portion of the colon. When physicians find an abnormality in this area, studies have suggested that it is predictive of abnormalities in the upper (proximal) portion of the colon. Therefore, these patients are referred for a colonoscopy, which is able to view the entire colon.

A total of 8,802 patients underwent a full colonoscopy within one year of an abnormal baseline flexible sigmoidoscopy in PLCO, with two-thirds of those patients having a follow-up colonoscopy within three months. Subjects with advanced adenomas in the distal colon were found to be at increased risk for having advanced adenomas in the proximal colon; however, subjects with only non-advanced distal adenomas were not at increased risk for advanced proximal adenomas. Specifically, 12 percent of subjects with advanced distal adenomas, 4 percent of subjects with (only) non-advanced distal adenomas, and 4 percent of subjects with no distal adenomas were found to have advanced proximal adenomas.

Reference: Pinsky PF, Schoen RE, et al. "Predictors of Advanced Proximal Neoplasia in Persons with Abnormal Screening Flexible Sigmoidoscopy." Clinical Gastroenterology and Hepatology. Vol. 1. 2003.

• In a group of patients who were found to have many polyps, radiologists were in agreement that virtual colonoscopy and traditional colonoscopy identified the same problems.

The evaluation of computed virtual colonoscopy as a non-invasive examination of the colon continues to face new challenges. Early estimates of the diagnostic performance of virtual colonoscopy have been promising but variable.

The purpose of this study was to evaluate reader agreement by a radiologist for colorectal polyp detection in a group of patients who had many polyps. This group of patients, who were suspected of having polyps, was first examined with virtual colonoscopy and then traditional colonoscopy the same day. The images were analyzed independently by four experienced radiologists.

A total of 157 colorectal lesions ranging from 4 millimeters to 30 millimeters were found at colonoscopy and correlated with virtual colonoscopy findings. Overall analysis demonstrated a 75 percent agreement among the four readers.

Reference: McFarland EG, Pilgram TK, et al. "CT Colonography: Multiobserver Diagnostic Performance." Radiology. Vol. 225. 2002.

• Approximately 70 percent of individuals who undergo screening sigmoidoscopy are satisfied and find the procedure more comfortable than expected, and only 15 percent to 25 percent find the procedure unpleasant. Physicians should not project discomfort to patients as a reason for not requesting screening sigmoidoscopy.

Physicians often cite patient discomfort as a reason for not requesting sigmoidoscopy, but patient experiences have not been well-studied. The researchers for this study adapted a survey which was designed to measure satisfaction with screening mammography. Questions about screening using flexible sigmoidoscopy centered on convenience, accessibility, staff interpersonal skills, physical surroundings, perceived technical competence, pain and discomfort, expectations and beliefs, and general satisfaction.

A total of 1,221 patients were surveyed after sigmoidoscopy. The results show that over 93 percent of the participants strongly agreed or agreed that they would be willing to undergo another examination, and 74.9 percent would strongly recommend the procedure to their friends. Regarding pain and discomfort, 76.2 percent strongly agreed or agreed that the examination did not cause a lot of pain, 78.1 percent stated that it did not cause a lot of discomfort, and 68.5 percent thought that it was more comfortable than expected. Fifteen percent to 25 percent of the patients indicated they had a lot of pain, great discomfort, or more discomfort than expected. Women were more likely to have significant pain or discomfort than men.

Reference: Schoen RE, Weissfeld JL, et al. "Patient Satisfaction with Screening Flexible Sigmoidoscopy." Archives of Internal Medicine. Vol. 160. June 26, 2000.

• Among experienced abdominal radiologists using virtual colonoscopy, the ability to find polyps was similar with 2-D and 3-D (two dimensional and three dimensional) display techniques, although individual cases showed improved results with 3-D display techniques. Evaluation of reader agreement (independent radiologists detecting the same abnormalities) demonstrated good agreement for 3-D display, but not as good for 2-D display.

Virtual colonoscopy is a rapidly growing and evolving technology for the detection of colorectal polyps and permits viewing with 2-D and 3-D display techniques. This method is being used as a potential noninvasive alternative for the detection of colorectal polyps.

Virtual colonoscopy was performed on 16 patients who were suspected of having polyps at a prior flexible sigmoidoscopy examination or barium enema examination. Three specific 2-D and 3-D display techniques were tested. Three experienced abdominal radiologists independently analyzed each test case and each patient was retested six weeks later.

The results of readings 1 and 2 were similar for both 2-D and 3-D techniques among the readers. Overall observer agreement was good for the 3-D display techniques; however, observer agreement for 2-D techniques was lower.

Reference: McFarland EG, Brink JA, et al. "Spiral CT Colonography: Reader Agreement and Diagnostic Performance with Two- and Three-Dimensional Image-Display Techniques." Radiology. Vol. 218. 2001.

Studies of Cancer Causes

• Cigarette use is a risk factor for developing colorectal adenomas. Inherited variations in two genes (NQ01 and CYP1A1), which influence the activation of the cancer-causing substances in tobacco smoke, were found to increase risk for developing colorectal adenomas.

In this study, researchers investigated the roles of variations in the CYP1A1 and NQ01 genes, combined with tobacco use, on the development of colorectal adenomas. These genes play a role in activating the cancer-causing substances in tobacco smoke. While tobacco use has been found to be a risk factor for developing colorectal adenomas, the role of these two genes is unclear. For this study, 772 people with at least one advanced adenoma and 777 people with no adenomas completed questionnaires about their lifestyles and had genetic tests done on their blood to determine if they had changes in these two genes.

The researchers found that the risk of having advanced colorectal adenomas was increased in smokers who had a variation in either the CYP1A1 gene or the NQ01 gene, and greatest in those with variations in both genes. In people who did not smoke, these gene variations did not affect their risk for developing colorectal adenomas.

Reference: Hou L, Chatterjee N, Huang WY, et al. "CYP1A1 Val₄₆₂ and NQ01 Ser₁₈₇ Polymorphisms, Cigarette Use, and Risk for Colorectal Adenoma." Carcinogenesis. Vol 26, No. 6. 2005.

• Microsomal epoxide hydrolase (EPHX1) is responsible for breaking down carcinogens in cigarette smoke. Variations in this gene that increase EPHX1 protein activity appeared to increase risk for colorectal adenoma, particularly among recent and current smokers.

Microsomal epoxide hydrolase (EPHX1) is a protein that breaks down polycyclic aromatic hydrocarbons found in cigarette smoke, which are known to cause cancer. However, in the process of breaking down these carcinogens, EPHX1 creates another carcinogen, benzo(a)pyrene 7,8 dihydrodiol 9,10 epoxide (BPDE).

Researchers looked at two variations in the EPHX1 gene that are thought to affect the level of activity of the EPHX1 protein. They compared 772 people with advanced colorectal adenoma to 777 people without the disease. Detailed information on smoking history was collected from a risk factor questionnaire that participants filled out when they enrolled in the PLCO study. Non-smokers were considered those who did not smoke cigarettes for more than six months or who did not smoke pipes or cigars for more than one year. Current or recent smokers were those who quit less than 10 years before enrollment in the study.

Researchers found that those participants with variations in the EPHX1 gene, which led to higher protein activity, had an increased risk of colorectal adenoma. This was especially true among recent and current smokers.

Reference: Huang W, Chatterjee N, et al. "Microsomal Epoxide Hydrolase Polymorphisms and Risk for Advanced Colorectal Adenoma." Cancer Epidemiology, Biomarkers & Prevention. Vol. 14, Issue 1. 2005.

• Even though iron has been suggested as a risk factor for colorectal cancer, there was no relationship found between dietary intake of iron and risk of colorectal adenomas, the precursor condition to colorectal cancer. In addition, genetic variations that increase levels of iron in the blood were not found to be related to adenoma risk.

Both iron intake and measures of iron in the blood have been suggested to be related to increases in the risk of colorectal cancer and adenoma. Researchers looked at iron intake and genetic variation in 679 people with advanced colorectal adenoma and 697 controls. Iron intake information was taken from participant responses to a food frequency questionnaire. Researchers found no relationship between iron intake and risk of adenoma.

Variations in the hemochromatosis gene (HFE) affects levels of iron in the blood. Researchers who looked at three different polymorphisms, or variations in this gene, did not find any relationship between the polymorphisms and risk of adenoma.

Reference: McGlynn KA, Sakoda LC, et al. "Hemochromatosis Gene Mutations and Distal Adenomatous Colorectal Polyps." Cancer Epidemiology, Biomarkers & Prevention. Vol. 14, Issue 1. 2005.

• People who had a high calcium intake, greater than 1200 mg/d (milligrams per day), had reduced risk of colorectal adenoma, a pre-cursor condition to cancer.

Calcium can reduce the risk of colorectal tumors by reducing exposure to harmful compounds in the bowel, or by influencing various cellular activities in the colon, such as cell growth and death. This study compared supplemental and dietary calcium intake of 3,696 people with adenoma to 34,817 controls. Calcium intake information was derived from individual responses on a food frequency questionnaire. Researchers found that people with the highest intakes of calcium had the lowest risk of colorectal adenoma. The association between intake and risk was stronger for calcium from nondairy foods and supplements, and for adenoma of the distal colon, the part of the colon farthest from the stomach.

Reference: Peters U, Chatterjee N, et al. "Calcium Intake and Colorectal Adenoma in a U.S. Colorectal Cancer Early Detection Program." American Journal of Clinical Nutrition. Vol. 80. 2004.

• Variations in the calcium-sensing receptor gene were associated with advanced colorectal adenoma, a precursor condition to cancer. Also, a protective association was found between total calcium intake and advanced colorectal adenoma risk.

The calcium-sensing receptor (CASR) is thought to mediate calcium's role in preventing cancer. Researchers looked at three common polymorphisms, or variations, in this gene in 772 people with advanced colorectal adenoma and 777 people without the disease. They found an association between advanced colorectal adenoma and these polymorphisms. This is the first study to evaluate variations in this gene in relation to risk of colorectal adenoma. Therefore, this study contributes new data that show a mediating role of CASR in preventing cancer.

This study also looked at calcium intake by reviewing participants' answers to a food frequency questionnaire which contained questions about dietary calcium intake and supplement use. A protective association was found for total calcium intake. For each additional 1,000 mg of calcium they took, participants had a 21 percent reduction in risk of advanced colorectal adenoma.

Reference: Peters U, Chatterjee N, et al. "Association of Genetic Variants in the Calcium-Sensing Receptor with Risk of Colorectal Adenoma." Cancer Epidemiology, Biomarkers & Prevention. Vol. 13, Issue 12. 2004.

• The VDR TaqI variation in the vitamin D receptor gene was not associated with risk of advanced colorectal adenoma, a pre-cursor condition to cancer. One vitamin D metabolite, 1,25(OH)2D, was not associated with advanced adenoma risk. Another vitamin D metabolite, 25(OH)D, was inversely associated with advanced adenoma risk in women but not in men.

Vitamin D may be involved in the prevention of colorectal cancer, and this action may be mediated by the vitamin D receptor (VDR). Researchers analyzed a polymorphism, or variation in the VDR gene, called VDR TaqI, in 763 people with advanced colorectal adenoma and 774 people without the disease. They found no association between this polymorphism and adenoma.

Researchers also measured blood serum levels of two vitamin D metabolites, 1,25(OH)2D and 25(OH)D, in a subset of 394 cases and 397 controls. They found that serum levels of 1,25(OH)2D were not associated with adenoma risk. However, for the second metabolite, 25(OH)D, researchers found that higher levels were associated with a decreased adenoma risk in women, but not in men. In women, when comparing those in the highest quintile with those in the lowest quintile, the risk of advanced adenoma decreased by 73 percent.

Reference: Peters U, Hayes RB, et al. "Circulating Vitamin D Metabolites, Polymorphism in Vitamin D Receptor, and Colorectal Adenoma Risk." Cancer Epidemiology, Biomarkers & Prevention. Vol. 13, Issue 4. 2004.

• People who had a high level of fiber in their diet were at lower risk of colorectal adenoma, a pre-cursor condition to cancer.

The potential impact of dietary fiber on colorectal cancer risk is controversial. Researchers examined fiber intake from food and supplements in 3,591 people with adenoma, and 33,971 people without the disease. They found that risk of adenoma decreased with increasing intake of dietary fiber in both men and women. People in the highest quintile of fiber intake, who consumed approximately 24 more grams of fiber per day than those people in the lowest quintile, had a 27 percent decrease in adenoma risk compared with those in the lowest quintile.

Reference: Peters U, Sinha R, et al. "Dietary Fibre and Colorectal Adenoma in a Colorectal Cancer Early Detection Programme." Lancet. Vol. 361. 2003.

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  (http://www.cancer.gov/cancertopics/factsheet/Detection/colorectal-screening)
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  (http://www.cancer.gov/cancertopics/types/colon-and-rectal)
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Glossary Terms

A graphic display of depth, width, and height. Also called 3-dimensional.

Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs.

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

A tumor that is not cancer. It starts in gland-like cells of the epithelial tissue (thin layer of tissue that covers organs, glands, and other structures within the body).

Any substance that causes the body to make a specific immune response.

A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray.

An initial measurement that is taken at an early time point to represent a beginning condition, and is used for comparison over time to look for changes. For example, the size of a tumor will be measured before treatment (baseline) and then afterwards to see if the treatment had an effect.

A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

The long, tube-shaped organ in the abdomen that completes the process of digestion. The bowel has two parts, the small bowel and the large bowel. Also called intestine.

A substance that may be found in high amounts in the blood of patients with certain types of cancer, including ovarian cancer. CA-125 levels may also help monitor how well cancer treatments are working or if cancer has come back. Also called cancer antigen 125.

A mineral needed for healthy teeth, bones, and other body tissues. It is the most common mineral in the body. A deposit of calcium in body tissues, such as breast tissue, may be a sign of disease.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Any substance that causes cancer.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

An x-ray of the structures inside the chest. An x-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Examination of the inside of the colon using a colonoscope, inserted into the rectum. A colonoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease.

Having to do with the colon or the rectum.

In science, a substance that is made up of more than one ingredient.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.

The process of identifying a disease, such as cancer, from its signs and symptoms.

The things a person eats and drinks.

The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum.

An examination in which a doctor inserts a lubricated, gloved finger into the rectum to feel for abnormalities. Also called DRE.

In medicine, refers to a part of the body that is farther away from the center of the body than another part. For example, the fingers are distal to the shoulder. The opposite is proximal.

The study of the patterns, causes, and control of disease in groups of people.

A record of the relationships among family members along with their medical histories. This includes current and past illnesses. A family history may show a pattern of certain diseases in a family. Also called family medical history.

In food, fiber is the part of fruits, vegetables, legumes, and whole grains that cannot be digested. The fiber in food may help prevent cancer. In the body, fiber refers to tissue made of long threadlike cells, such as muscle fiber or nerve fiber.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

The study of genes and heredity. Heredity is the passing of genetic information and traits (such as eye color and an increased chance of getting a certain disease) from parents to offspring.

A condition in which the body takes up and stores more iron than it needs. The extra iron is stored in the liver, heart, and pancreas, which may cause liver disease, heart problems, organ failure, and cancer. It may also cause bronze skin, diabetes, pain in the joints and abdomen, tiredness, and impotence. Hemochromatosis may be inherited, or it may be caused by blood transfusions. Also called iron overload.

A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn disease.

Transmitted through genes that have been passed from parents to their offspring (children).

The group receiving the study agent that is being tested in a clinical trial or clinical study.

The long, tube-shaped organ in the abdomen that completes the process of digestion. The intestine has two parts, the small intestine and the large intestine. Also called bowel.

An important mineral the body needs to make hemoglobin, a substance in the blood that carries oxygen from the lungs to tissues throughout the body. Iron is also an important part of many other proteins and enzymes needed by the body for normal growth and development. It is found in red meat, fish, poultry, lentils, beans, and foods with iron added, such as cereal.

An area of abnormal tissue. A lesion may be benign (not cancer) or malignant (cancer).

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

The use of film or a computer to create a picture of the breast.

In medicine, a lump in the body. It may be caused by the abnormal growth of cells, a cyst, hormonal changes, or an immune reaction. A mass may be benign (not cancer) or malignant (cancer).

A substance made or used when the body breaks down food, drugs or chemicals, or its own tissue (for example, fat or muscle tissue). This process, called metabolism, makes energy and the materials needed for growth, reproduction, and maintaining health. It also helps get rid of toxic substances.

A measure of weight. A milligram is approximately 450,000 times smaller than a pound and 28,000 times smaller than an ounce.

A measure of length in the metric system. A millimeter is one thousandth of a meter. There are 25 millimeters in an inch.

In medicine, to regularly watch and check a person or condition to see if there is any change. Also refers to a device that records and/or displays patient data, such as for an electrocardiogram (EKG).

The state of being mortal (destined to die). Mortality also refers to the death rate, or the number of deaths in a certain group of people in a certain period of time. Mortality may be reported for people who have a certain disease, live in one area of the country, or who are of a certain gender, age, or ethnic group.

The moist, inner lining of some organs and body cavities (such as the nose, mouth, lungs, and stomach). Glands in the mucosa make mucus (a thick, slippery fluid). Also called mucous membrane.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.

In medicine, it describes a procedure that does not require inserting an instrument through the skin or into a body opening. In cancer, it describes disease that has not spread outside the tissue in which it began.

Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).

A collection of information about a person’s health. It may include information about allergies, illnesses and surgeries, and dates and results of physical exams, tests, screenings, and immunizations. It may also include information about medicines taken and about diet and exercise. Also called personal health record and personal medical history.

Medical doctor.

A common change in the genetic code in DNA. Polymorphisms can have a harmful effect, a good effect, or no effect. Some polymorphisms have been shown to increase the risk of certain types of cancer.

Growths that may become cancer that protrude from a mucous membrane.

In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

A protein made by the prostate gland and found in the blood. Prostate-specific antigen blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland. Also called PSA.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

In medicine, refers to a part of the body that is closer to the center of the body than another part. For example, the knee is proximal to the toes. The opposite is distal.

A protein made by the prostate gland and found in the blood. PSA blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland. Also called prostate-specific antigen.

A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell.

The last several inches of the large intestine closest to the anus.

Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

A drug or substance used to calm a person down, relieve anxiety, or help a person sleep.

The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.

Examination of the lower colon using a sigmoidoscope, inserted into the rectum. A sigmoidoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease. Also called proctosigmoidoscopy.

An organ that is part of the digestive system. The stomach helps digest food by mixing it with digestive juices and churning it into a thin liquid.

The material in a bowel movement. Stool is made up of undigested food, bacteria, mucus, and cells from the lining of the intestines. Also called feces.

Adding nutrients to the diet.

A group or layer of cells that work together to perform a specific function.

A plant with leaves that have high levels of the addictive chemical nicotine. The leaves may be smoked (in cigarettes, cigars, and pipes), applied to the gums (as dipping and chewing tobacco), or inhaled (as snuff). Tobacco leaves also contain many cancer-causing chemicals, and tobacco use and exposure to secondhand tobacco smoke have been linked to many types of cancer and other diseases. The scientific name is Nicotiana tabacum.

A procedure used to examine the vagina, uterus, fallopian tubes, ovaries, and bladder. An instrument is inserted into the vagina that causes sound waves to bounce off organs inside the pelvis. These sound waves create echoes that are sent to a computer, which creates a picture called a sonogram. Also called transvaginal sonography and TVS.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A method to examine the inside of the colon by taking a series of x-rays. A computer is used to make 2-D and 3-D pictures of the colon from these x-rays. The pictures can be saved, changed to better viewing angles, and reviewed after the procedure, even years later. Also called computed tomographic colonography, computed tomography colonography, CT colonography, and CTC.

Necessary to maintain life. Breathing is a vital function.

A nutrient that the body needs in small amounts to function and stay healthy. Vitamin D helps the body use calcium and phosphorus to make strong bones and teeth. It is fat-soluble (can dissolve in fats and oils) and is found in fatty fish, egg yolks, and dairy products. Skin exposed to sunshine can also make vitamin D. Not enough vitamin D can cause a bone disease called rickets. It is being studied in the prevention and treatment of some types of cancer. Also called cholecalciferol.