Tuesday, June 29, 2010

Summary of Common Cancer Diagnostic Techniques

Common Cancer Diagnostic Techniques
The procedure that takes a sample of tissue to test whether a lump represents cancer is called a biopsy, and the tissue sample is called the biopsy specimen. Some types of biopsies remove an entire organ. Other types of biopsies may remove tumor samples through a thin needle or through an endoscope.
There are 2 types of needle biopsies: fine needle biopsy (also called fine needle aspiration) and core needle biopsy (also called core biopsy). Fine needle aspiration (FNA) uses a very thin needle and a syringe to withdraw a small amount of fluid and very small pieces of tissue from the tumor. The main advantages of FNA are that it does not require cutting through the skin and that in some cases it is possible to make a diagnosis the same day. The disadvantage is that sometimes this needle cannot remove enough tissue for a definite diagnosis. Core biopsy uses needles that are slightly larger than those used in FNA. They remove a small cylinder of tissue (about 1/16 inch in diameter and 1/2 inch long). The core needle biopsy is done using local anesthesia.
Excisional or incisional biopsy - with this type of biopsy, a surgeon cuts through the skin to remove the entire tumor (excisional biopsy) or a small part of a large tumor (incisional biopsy).
Endoscopic biopsy - an endoscope is a thin, flexible, lighted tube that has a lens or a video camera on the end. It can allow a doctor to look inside different parts of the body. Tissue samples can also be taken out through the endoscope to find out if cancer is present and, if so, the type.
Skin biopsies - there are many ways to take a biopsy of the skin. Shave biopsies remove the outer layers of skin and are fine for some basal cell or squamous cell skin cancers. Punch biopsies or excisional biopsies remove deeper layers of the skin, and can find out how deeply a melanoma has gone into the skin - an important factor in choosing treatment for that type of cancer.
Sentinel lymph node mapping and biopsy - lymph node mapping helps the surgeon know which lymph nodes to remove for an excisional biopsy. Sentinel node mapping and biopsy has become a common way to find out whether the cancer (especially melanoma and breast cancer) has spread to the lymph nodes. This procedure can find the lymph nodes that drain lymph fluid from the area where the cancer started. If the cancer has spread, these lymph nodes are usually the first place it will go.
Endoscopy is a medical procedure that uses tube-like instruments (called endoscopes.) These are put into the body to look inside. There are many different kinds of endoscopes, or "scopes." Some are hollow and allow the doctor to look right into the body. Others use fiber optics - flexible glass or plastic fibers that transmit light. Still others have small video cameras on the end that put pictures on computer screens. Depending on the area of the body being looked at, the endoscope may be put in through an opening like the mouth, anus, or urethra (the tube that carries urine out of the bladder). In some cases, the endoscope is put in through a small cut (incision) made in the skin. Some types of endoscopes can be used to look for cancer in people who have no symptoms. For example, colonoscopy and sigmoidoscopy are used to screen for colon and rectal cancer.
Diagnosing diseases by looking at single cells and small clusters of cells is called cytology or cytopathology. While the pieces of tissue in biopsy samples may be as small as 1/16 inch or much larger (several inches), the individual cells and the cell clusters in cytology samples are usually too small to see without a microscope. Compared with tissue biopsy, a cytology specimen usually: is easier to get; causes less discomfort to the patient; is less likely to result in serious complications; costs less. The disadvantage is that, in some cases, a tissue biopsy result is more accurate, though in many cases the cytology fluid may be just as accurate.
Body fluids - fluids from cavities and spaces in the body can be tested to see if cancer cells are present. Some of the body cavity fluids tested in this way include: urine; sputum (phlegm); spinal fluid; pleural fluid (from the space around the lungs); pericardial fluid (from the sac that surrounds the heart); ascitic fluid (from the space in the belly).
Scrape or brush cytology - another cytology technique is to gently scrape or brush some cells from the organ or tissue being tested. The best-known cytology test that samples cells in this way is the Pap test. Pap test samples are taken by using a small spatula and/or brush to remove cells from the cervix (the lower part of the uterus or womb). Other areas that can be brushed or scraped include the esophagus (swallowing tube), stomach, bronchi (breathing tubes that lead to the lungs), and mouth.
Histochemical stains - these tests use different chemical dyes that are attracted to certain substances found in some types of cancer cells. An example is the mucicarmine stain, which is attracted to mucus. Droplets of mucus inside a cell that are exposed to this stain will look pink-red under a microscope. This stain is useful if the pathologist suspects, for example, an adenocarcinoma (a glandular type of cancer) in a lung biopsy. Adenocarcinomas can produce mucus, so finding pink-red spots in lung cancer cells will tell the pathologist that the diagnosis is adenocarcinoma.
Immunohistochemical stains - immunohistochemical (IHC) or immunoperoxidase stains are another very useful category of special tests. The principle of this method is that an antibody will attach itself to certain substances (antigens) that are on or in the cell. Certain types of normal cells and cancer cells have unique different antigens. To find out if the antibodies have been attracted to the cells, chemicals are added that cause the cell to change color only if a certain antibody (and, therefore, the antigen) is present. IHC stains are useful in identifying certain types of cancers. If the cancer started in the lymph node, the diagnosis would be lymphoma. If the cancer started in another part of the body and spread to the lymph node, it might be metastatic cancer.
Electron microscopy - the typical medical lab microscope uses a beam of ordinary light to look at specimens; whereas electron microscope uses beams of electrons. The electron microscope's magnifying power is about 1,000 times greater than that of an ordinary light microscope. This degree of magnification is rarely needed in deciding whether a cell is cancer. But it sometimes helps find very tiny details of a cancer cell's structure that provide clues to the exact type of the cancer.
Flow cytometry - this test is often used to test the cells from bone marrow, lymph nodes, and blood samples. It is very accurate in finding out the exact type of leukemia or lymphoma a person has. It also helps to tell lymphomas from non-cancer lymph node diseases. A sample of cells from a biopsy, cytology specimen, or blood specimen is treated with special antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of cells that contain the antigens that fit with it. If the sample contains those cells, the laser will cause them to give off light that is then measured and analyzed by a computer.
Image cytometry – similar to flow cytometry, this test uses dyes that react with DNA. But instead of suspending the cells in a stream of liquid and analyzing them with a laser, image cytometry uses a digital camera and a computer to measure the amount of DNA in cells on a microscope slide.
Cytogenetics - normal human cells contain 46 chromosomes. Some types of cancer have a unique abnormal chromosome. Recognizing the abnormal chromosome helps to identify those types of cancer. This is especially useful in diagnosing some lymphomas, leukemias, and sarcomas.
Fluorescent in situ hybridization (FISH) is a newer test that is much like cytogenetic testing. It can find most chromosome changes that can be seen under a microscope in standard cytogenetic tests. It can also find some changes too small to be seen with usual cytogenetic testing. FISH uses special fluorescent dyes that only attach to specific parts of certain chromosomes. FISH can find chromosome changes such as translocations, which are important to help classify some kinds of leukemia. This test can also show when there are too many copies of a certain gene, which sometimes can help doctors choose the best treatment options.
Molecular genetic tests can identify mutations (abnormal changes) in certain areas of DNA that are responsible for controlling cell growth. Some of these mutations may cause cancers to be especially aggressive in growing and spreading. In some cases, identifying certain mutations can help doctors choose treatments that are more likely to work.
Polymerase chain reaction (PCR) - is a very sensitive molecular genetic test for finding specific DNA sequences, such as those occurring in some cancers. Reverse transcriptase PCR (RT-PCR) is a method used to detect small amounts of RNA. RT-PCR can be used to find and classify cancer cells. RT-PCR can also be used to sub-classify cancer cells.
Gene expression microarrays - the advantage of this technology is that relative levels of hundreds or even thousands of different RNA molecules from one sample can be compared at the same time. The results tell which genes are active in a tumor.
Imaging tests are studies that make pictures (images) of what's going on inside a body. These tests use forms of energy (x-rays, sound waves, radioactive particles, or magnetic fields) that are passed through the body. The changes in energy patterns made by body tissues can be seen with special devices, which change them into pictures. These pictures can show normal body structure and function as well as abnormal ones caused by diseases such as cancer.
Computed tomography scan (CT scan, CAT scan, and spiral or helical CT) - CT scans show a slice, or cross-section, of the body. CT scans use controlled amounts of x-rays to create images. Whereas a standard x-ray uses a broad beam of radiation, a CT scan uses a pencil-thin beam to create a series of pictures taken from different angles. The image shows organs and soft tissues more clearly than standard x-rays. Because the picture is made by a computer, it can be enlarged to make it easier to see and interpret. CT scans can show a tumor's shape, size, and location, and even the blood vessels that feed the tumor - all without having to cut into the patient. CT scans are good at finding and getting information about cancer in the liver, pancreas, adrenal glands, lungs, and bones. They are also used to collect information about cancer in the large and small intestines, swallowing tube (esophagus), stomach, brain, prostate, or other organs. In recent years, spiral CT (also known as helical CT) has become the most common type of CT used. It uses a better and faster machine that uses less radiation than the original CT scanner.
Magnetic resonance imaging (MRI, magnetic resonance (MR), and nuclear magnetic resonance (NMR) imaging) - like CT scans, MRI displays a cross-section of a body. But MRI uses strong magnets instead of radiation to create the images. MRI creates pictures of soft tissue parts of the body that are sometimes hard to see using other imaging tests. MRI is good at finding and pinpointing cancer in the brain, spinal cord, head, neck, and bones and muscles. An MRI done with contrast is the best way to see brain tumors. Using MRI, doctors can sometimes tell a non-cancerous (benign) tumor from a cancerous (malignant) one.
Radiographic studies (regular x-rays and contrast studies) (also called radiographs and roentgenograms) - radiographs, most often called x-rays, produce shadow-like images of certain organs or tissues. X-rays are very good at finding certain bone problems. X-rays can show some organs or soft tissues, but MRI and CT scans often give better pictures of them. Still, x-rays are often faster, easy to get, and cost less than newer scans, so they may be used to get information quickly. An x-ray of the belly may show tumors or other diseases in organs like the intestines, stomach, liver, spleen, and kidneys. A chest x-ray can help find lung diseases, including cancer. These tests, which make a single image or series of images, are sometimes called standard radiographic studies. Mammograms (breast x-rays) are another form of radiographic study.
Special types of x-ray tests may use dyes called contrast materials. Contrast studies provide some information that standard x-ray cannot. During a contrast study, one gets a dose of a contrast material that outlines, highlights, or fills in parts of the body so that they show up more clearly on an x-ray. The contrast material may be given by mouth, as an enema, as an injection, or through a catheter put into various tissues of the body. For most of these tests, the images can be captured either on x-ray film or by a computer.
Nuclear scans (nuclear imaging, radionuclide imaging, and nuclear medicine scans) - nuclear scans make pictures based on the body's chemistry rather than on physical shapes and forms. They use substances called radionuclides (also known as tracers or radiopharmaceuticals) that release low levels of radiation. The amount of radioactivity used is very small and not known to cause harm. Body tissues affected by certain diseases, such as cancer, may absorb more or less of the tracer than normal tissues. Special cameras pick up the pattern of radioactivity to create images that show where the material travels and where it collects. The scans show certain disorders of internal organs and tissues better than standard x-ray images. Nuclear scans are used to find tumors, especially in the bones and thyroid gland. They are also used to study a cancer's stage and to decide if treatment is working.
Radionuclide scans: Radionuclides send out gamma rays which are picked up by a special camera (known as a gamma camera, rectilinear scanner, or scintiscan). The signals are processed by a computer, which turns them into 2- or 3-dimensional (3-D) images, sometimes with color added for extra clarity.
Positron emission tomography scans - positron emission tomography (PET) is a scan that uses a form of radioactive sugar. Body cells take in different amounts of the radioactive sugar, depending on how fast they are growing. Cancer cells, which grow quickly, are more likely to take up larger amounts of the sugar than normal cells. The radioactive sugar gives off tiny atomic particles called positrons, which run into electrons in the body, giving off gamma rays. A special camera picks up these rays as they leave the body and turns them into pictures. PET scans are most often used to find cancer. PET scans are especially useful for studying the brain. They are also widely used to look at cancers of the head and neck, thyroid, esophagus (swallowing tube), breast, colon, rectum, ovary, and lung, as well as melanomas and lymphomas.
PET/CT scans: A newer imaging machine combines PET scans with CT scans. PET/CT scanners give more detailed information on the location of any increased cell activity, helping doctors to pinpoint tumors. They are now commonly being used.
Ultrasound (ultrasonography, sonography, or sonogram) - an ultrasound machine creates images called sonograms by giving off high-frequency sound waves that go through a body. As the sound waves bounce off organs and tissues, they create echoes. Ultrasound is good at giving pictures of some diseases of soft tissues that do not show up well on x-rays. Ultrasound is also a good way to tell fluid-filled cysts from solid tumors because they make very different echo patterns. Ultrasound can also be used to find out how far a tumor of the esophagus (swallowing tube), rectum, or uterus (womb) has gone through the wall of the organ.

References: All the data in this article are provided by the American Cancer Society.

1. American Cancer Society. 2010
2. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009
3. American Cancer Society: Early Detection. 2010

Friday, June 4, 2010

A Review Article on Genes and Proteins

In medicine, a biomarker can be referred to anything that can be used as an indicator of a particular disease state or some other biological state of an organism. Biomarkers can be genes, proteins, small molecules, or hormones. Commonly, for the purposes of diagnostics, biomarkers are broadly divided in two groups – one group encompasses genetic markers such as DNA or RNA; and the other – proteins, hormones or small molecules. In essence, DNA testing examines DNA molecule itself, and protein testing examines changes in protein concentration or alterations in its structure. To understand the difference between these two groups, it is important to define genes, proteins and how proteins are synthesized based on the genetic code.
A gene is a unit of heredity in an organism. It is normally a strand of DNA that codes for a type of protein or for an RNA chain in the organism. All proteins and functional RNA chains are specified by genes. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring.
Proteins (also known as polypeptides) are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code (1).
In all organisms, there are two major steps separating a protein-coding gene from its protein: First, the DNA on which the gene resides must be transcribed from DNA to messenger RNA (mRNA); and, second, it must be translated from mRNA to protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule itself is called a gene product.
Transcription is a genetic process that produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The DNA strand whose sequence matches that of the RNA is known as the coding strand and the strand from which the RNA was synthesized is the template strand.
Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein. Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds.
As mentioned above, gene tests (also called DNA-based tests) involve direct examination of the DNA molecule itself. Genetic testing allows the genetic diagnosis of vulnerabilities to inherited diseases, and can also be used to determine a child's paternity (genetic father) or a person's ancestry. Normally, every person carries two copies of every gene, one inherited from their mother, one inherited from their father. In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases, or mutant forms of genes associated with increased risk of developing genetic disorders. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder.
Diagnostic DNA testing is used to diagnose or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical mutations and symptoms. Diagnostic testing can be performed at any time during a person's life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person's choices about health care and the management of the disease.
Predictive and presymptomatic types of DNA testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person's chances of developing disorders with a genetic basis.
The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done.
A positive test result means that the laboratory found a change in a particular gene, or chromosome of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease in the future, or suggest a need for further testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition.
A negative test result means that the laboratory did not find a dangerous copy of the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result.
In some cases, a negative result might not give any useful information. This type of result is called uninformative. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result.
Testing for protein biomarkers is generally more straightforward – a change in the quantity of a certain biomarker normally signals of the presence of a disease or a pathological condition. For instance, it is widely known that C-reactive protein (CRP) is a marker for inflammation; or that matrix metalloproteases are markers for cancer (2,3).
Other examples include pregnancy tests or immunohistochemical tests performed by pathologists to diagnose cancer.
Modern pregnancy tests look for chemical markers associated with pregnancy. These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The most commonly used marker is human chorionic gonadotropin (hCG), that was discovered in 1930 to be produced by the trophoblast cells of the fertilised ovum (blastocyst). The presence of this marker normally indicates that a woman is pregnant.
Immunohistochemistry (IHC) is also a straightforward process of localizing antigens (proteins) in cells of a tissue section using the principle of antibodies binding specifically to antigens in biological tissues (4). It takes its name from the roots "immuno," in reference to antibodies used in the procedure, and "histo," meaning tissue. IHC is a very good detection technique and has the advantage of being able to show exactly where a given protein is located within the tissue examined. Immunohistochemical staining is widely used in diagnostic surgical pathology for typing tumors (e.g. immunostaining for e-cadherin to differentiate between DCIS (ductal carcinoma in situ: stains positive) and LCIS (lobular carcinoma in situ: does not stain positive) (5); or cytokeratins for identification of carcinomas (6).

References:
1. Ridley, M. (2006). Genome. New York, NY: Harper Perennial.
2. Eiji Sunami, Nelson Tsuno, Takuya Osada, Shinsuke Saito, Joji Kitayama, Shigeru Tomozawa, Takashi Tsuruo, Yoichi Shibata, Tetsuichiro Muto, Hirokazu Nagawa:”MMP-1 is a Prognostic Marker for Hematogenous Metastasis of Colorectal Cancer”, The Oncologist, Vol. 5, No. 2, 108-114, April 2000
3. Pia Vihinen, Veli-Matti Kähäri: “Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets”, International Journal of Cancer, Volume 99 Issue 2, Pages 157 – 166, 12 Mar 2002.
4. Ramos-Vara, JA (2005). "Technical Aspects of Immunohistochemistry". Vet Pathol 42 (4): 405–426
5. O'Malley F and Pinder S, Breast Pathology, 1st. Ed. Elsevier 2006.
6. Leader M, Patel J, Makin C, Henry K (December 1986). "An analysis of the sensitivity and specificity of the cytokeratin marker CAM 5.2 for epithelial tumours. Results of a study of 203 sarcomas, 50 carcinomas and 28 malignant melanomas". Histopathology 10 (12): 1315–24.

Thursday, May 27, 2010

Genetic Testing – Does it Detect Cancer?

The term “genetic testing” used in this article encompasses all tests and methods thought to identify cancer or the predisposition for cancer via analyzing DNA or RNA of an organism. It can be further divided in two general groups – tests that screen host (human) DNA for mutations (genetic testing) and tests that identify the presence of parasite DNA (bacterial or viral).
One of the most useful examples of a genetic test is one that screens for parasite DNA associated with human papillomavirus (HPV). Scientific research showed that persistent HPV infections could be one of the causes of cervical cancer. In 2007, it was estimated that 11,000 women in the United States would be diagnosed with this type of cancer and nearly 4,000 would die from it. Cervical cancer affects nearly half a million women each year worldwide, claiming a quarter of a million lives. Studies also suggest that HPVs may play a role in some cancers of the anus, vulva, vagina, and penile cancer (cancer of the penis) (1). In addition, studies have found that oral HPV infection could be a risk factor for oropharyngeal cancer (cancer that forms in the middle part of the throat and includes the soft palate, the base of the tongue, and the tonsils) (1,2).
Some types of HPV are referred to as “low-risk” viruses because they rarely cause lesions that develop into cancer. HPV types that are more likely to lead to the development of cancer are referred to as “high-risk.” Both high-risk and low-risk types of HPV can cause the growth of abnormal cells, but only the high-risk types of HPV can lead to cancer. Sexually transmitted, high-risk HPVs include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73 (3). HPV types 16 and 18 together accompany about 70 percent of cervical cancers (3, 4).
It is important to note, though, that presence of HPV only signals of the increased risk of developing cancer, it does not detect cancer cells. The great majority of high risk HPV infections go away on their own without causing any type of abnormality. Even among the women who do develop abnormal cell changes with high-risk types of HPV, only a small percentage would develop cervical cancer if the abnormal cells were not removed. Studies suggest that whether a woman develops cervical cancer depends on a variety of factors acting together with high-risk HPVs (5). The factors that may increase the risk of cervical cancer in women with HPV infection include smoking and having many children (5).
Genetic testing is a process that looks for inherited genetic alterations that may increase the risk of certain cancers. This type of testing may show whether the risk in a family is passed through their genes. There is evidence that some kinds of cancer, such as breast and ovarian cancer, seem to run in families.
A genetic test for breast and ovarian cancer risk will not yield a simple "yes" or "no" answer. If a gene alteration is found, this will indicate that a person has an increased risk of getting cancer, but it will not tell if or when cancer will develop. If an alteration is not found, it still is no guarantee that cancer won't develop.
In recent years, several gene mutations have been discovered that were thought to increase a woman's risk of breast cancer. These alterations are most often found in genes named BRCA1 and BRCA2 (BReast CAncer Gene 1 and BReast CAncer Gene 2). Both men and women have BRCA1 and BRCA2 genes, so alterations in these genes can be passed down from either the mother or the father.
A woman with a BRCA1 or BRCA2 alteration were thought to be at higher risk for developing breast, ovarian, and other cancers than a woman without an alteration. However, not every woman who has an altered BRCA1 or BRCA2 gene will get cancer, because genes are not the only factor that affects cancer risk.
A positive test result generally indicates that a person has inherited a known harmful mutation in BRCA1 or BRCA2 and, therefore, thought to have an increased risk of developing certain cancers. However, a positive test result provides information only about a person’s risk of developing cancer. It cannot tell whether an individual will actually develop cancer or when.
Moreover, a recent report (6) published by scientists from the U.S. National Cancer Institute (NCI) suggests that DNA doesn't predict breast cancer risk much better than a questionnaire.
In theory, testing for BRCA1 or BRCA2 could allow women to make more informed choices about how often to undergo routine mammograms, for example, or, more radically, whether to take anticancer drugs like tamoxifen prophylactically. These decisions are currently made by patients, in consultation with clinicians, based on a predicted risk of cancer provided by the so-called Gail model. This model calculates a risk based on the answers to seven questions, including the age at which a woman began menstruating, the age at which she had her first child, and the number of relatives with breast cancer (6, 7)
To find out how well genetic screening measured up to the question-based Gail model, researchers pooled data from five of the studies originally used to identify the breast cancer genetic risk factors. Then they retrospectively calculated a prediction of cancer risk based on each woman's data for the 10 genetic risk factors known at the outset of the study.
They asked a very simple question: “what is the probability that a woman selected at random from the group that did go on to develop cancer would have a higher risk prediction than a randomly selected woman who did not?” For a completely useless model, the answer would be 50%; for a perfect model, the answer would be 100%. The answer for the genetic screening was 59.7%, whereas the answer for the question-based Gail model was 58%. By combining the two, the researchers were able to produce a model with a predictive power of 61.8%. But that combination didn't impact the prediction of risk, also called the score, very much for most individual patients (6, 7). Cancer epidemiologist Dr. Pharoah, who published a similar report in 2008 in New England Journal of Medicine based on just seven genetic risk factors, came to the same conclusion that genetic tests don't add a whole lot to the Gail model (8).
A recent study from Roche’s biotechnology unit in California discovered 50,000 genetic mutations associated with lung cancer (9). It is suggested that the number of genetic mutations correlates with the number of cigarettes smoked, and in this specific case smoking 3 cigarettes is associated with 1 genetic mutation. This type of analysis required costly whole genome sequencing, and provides an example of the impractical uses of genetic testing for identifying disease. With over 50,000 genetic mutations to choose from, it will be difficult for the medical to rely on this evidence.

References:
1. Parkin DM. The global health burden of infection-associated cancers in the year 2002. International Journal of Cancer 2006; 118:3030–3044.
2. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New England Journal of Medicine 2007; 356:1944–1956.
3. Munoz N, Bosch FX, Castellsague X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. International Journal of Cancer 2004;111:278–285.
4. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. The Lancet 2007; 370:890–907.
5. National Cancer Institute. Future directions in epidemiologic and preventive research on human papillomaviruses and cancer. Proceedings of a workshop. Bethesda, Maryland, June 2002. Journal of the National Cancer Institute Monographs 2003; 31:1–130.
6. Wacholder, S. et al, “Performance of common genetic variants in breast-cancer risk models”, New England Journal of Medicine, 362, 11, 986-983, 2010.
7. Wogan T. “Genetic Testing for Cancer Risk Not Clinically Useful”, ScienceNOW, March 17, 2010
8. Pharoah PDP, Antoniou AC, Easton DF, Ponder BAJ “Polygenes, Risk Prediction, and Targeted Prevention of Breast Cancer”, New England Journal of Medicine, 358, 2796, June 26, 2008
9. Steenhuysen, J. “U.S. gene study reveals toll of heavy smoking”, Reuters May 26, 2010. http://www.reuters.com/article/idUSTRE64P62Z20100526

Friday, May 14, 2010

Cancer Signs and Symptoms

Although most signs and symptoms arrive in the late stages of cancer, it is still important to know what they are and what cancers they correspond to. A doctor’s evaluation of signs and symptoms can lead to further tests or perhaps nothing at all, which can be the difference between life or death. A sign is a signal which can be seen and measured and indicate that something is not right in the body, and a symptom cannot be seen nor measured. For instance, related to colorectal cancer, blood in the stool is a sign while pain in the abdomen is a symptom.
Symptoms are noticed by the person who has them, but may not be easily seen by a physician. Having one sign or symptom may not be enough to figure out what's causing it. Sometimes, a patient's signs and symptoms still don't give the doctor enough clues to figure out the cause of an illness. Then medical tests, such as x-rays, blood tests, or a biopsy may be needed.
Cancer is a group of diseases that can cause almost any sign or symptom. The signs and symptoms will depend on where the cancer is, how big it is, and how much it affects the organs or tissues. If a cancer has spread (metastasized), signs or symptoms may appear in different parts of the body. As a cancer grows, it can begin to push on nearby organs, blood vessels, and nerves. This pressure causes some of the signs and symptoms of cancer. If the cancer is in a critical area, such as certain parts of the brain, even the smallest tumor can cause symptoms.
A cancer may also cause symptoms like fever, extreme tiredness (fatigue), or weight loss. This may be because cancer cells use up much of the body's energy supply, or they may release substances that change the way the body makes energy from food. Or the cancer may cause the immune system to react in ways that produce these symptoms. Sometimes, cancer cells release substances into the bloodstream that cause symptoms which are not usually linked to cancer. For example, some cancers of the pancreas can release substances which cause blood clots in veins of the legs. Some lung cancers make hormone-like substances that raise blood calcium levels. This affects nerves and muscles, making the person feel weak and dizzy.
There are some general signs and symptoms of cancer. But having any of these does not mean that it is cancer - many other things cause these signs and symptoms, too.
• Unexplained weight loss: Most people with cancer will lose weight at some point. When a person loses weight with no known reason, it's called an unexplained weight loss. An unexplained weight loss of 10 pounds or more may be the first sign of cancer. This happens most often with cancers of the pancreas, stomach, esophagus, or lung.
• Fever: Fever is very common with cancer, but it more often happens after cancer has spread from where it started. Almost all patients with cancer will have fever at some time, especially if the cancer or its treatment affects the immune system. This can make it harder for the body to fight infection. Less often, fever may be an early sign of cancer, such as blood cancers like leukemia or lymphoma.
• Fatigue: Fatigue is extreme tiredness that does not get better with rest. It may be an important symptom as cancer grows. It may happen early, though, in cancers like leukemia. Some colon or stomach cancers can cause blood loss. This is another way cancer can cause fatigue.
• Pain: Pain may be an early symptom with some cancers like bone cancers or testicular cancer. A headache that does not go away or get better with treatment may be a symptom of a brain tumor. Back pain can be a symptom of cancer of the colon, rectum, or ovary. Most often, pain due to cancer is a symptom of cancer that has already spread from where it started (metastasized).
• Skin changes: Along with cancers of the skin, some other cancers can cause skin symptoms or signs that can be seen. These signs and symptoms include:
o Darker looking skin (hyperpigmentation)
o Yellowish skin and eyes (jaundice)
o Reddened skin (erythema)
o Itching (pruritis)
• Excessive hair growth
o Along with the general symptoms, there are certain other common symptoms and signs which could suggest cancer. Again, there may be other causes for each of these, but it is important to see a doctor about them as soon as possible.
• Change in bowel habits or bladder function: Long-term constipation, diarrhea, or a change in the size of the stool may be a sign of colon cancer. Pain when passing urine, blood in the urine, or a change in bladder function (such as needing to pass urine more or less often than usual) could be related to bladder or prostate cancer. Report any changes in bladder or bowel function to a doctor.
• Sores that do not heal: Skin cancers may bleed and look like sores that do not heal. A long-lasting sore in the mouth could be an oral cancer. This should be dealt with right away, especially in people who smoke, chew tobacco, or often drink alcohol. Sores on the penis or vagina may either be signs of infection or an early cancer.
• White patches inside the mouth or white spots on the tongue: White patches inside the mouth and white spots on the tongue may be leukoplakia. Leukoplakia is a pre-cancerous area that is caused by frequent irritation. It is often caused by smoking or other tobacco use. People who smoke pipes or use oral or spit tobacco are at high risk for leukoplakia. If it is not treated, leukoplakia can become oral cancer.
• Unusual bleeding or discharge: Unusual bleeding can happen in early or advanced cancer. Blood in the sputum (phlegm) may be a sign of lung cancer. Blood in the stool (or a dark or black stool) could be a sign of colon or rectal cancer. Cancer of the cervix or the endometrium (lining of the uterus) can cause abnormal vaginal bleeding. Blood in the urine may be a sign of bladder or kidney cancer. A bloody discharge from the nipple may be a sign of breast cancer.
• Thickening or lump in the breast or other parts of the body: Many cancers can be felt through the skin. These cancers occur mostly in the breast, testicle, lymph nodes (glands), and the soft tissues of the body. A lump or thickening may be an early or late sign of cancer and should be reported to a doctor, especially if you've just found it or notice it has grown in size.
• Indigestion or trouble swallowing: Indigestion or swallowing problems may be signs of cancer of the esophagus (the swallowing tube that goes to the stomach), stomach, or pharynx (throat). But like most symptoms on this list, they are most often caused by something other than cancer.
• Recent change in a wart or mole or any new skin change: Any wart, mole, or freckle that changes color, size, or shape, or that loses its sharp border should be seen by a doctor right away. Any other skin changes should be reported, too. A skin change may be a melanoma which, if found early, can be treated successfully.
• Nagging cough or hoarseness: A cough that does not go away may be a sign of lung cancer. Hoarseness can be a sign of cancer of the voice box (larynx) or thyroid gland.
• The signs and symptoms listed above are the ones more commonly seen with cancer, but there are many others that are less common and are not listed here.
But sometimes cancer starts in places where it will not cause any symptoms until it has grown quite large. One example is cancers in the pancreas. They usually do not cause symptoms until they grow large enough to press on nearby nerves or organs (this causes back or belly pain). Others grow around the bile duct and block the flow of bile. This causes the eyes and skin to look yellow (jaundice). By the time a pancreatic cancer causes these signs or symptoms, it is usually in an advanced stage. This means it has grown and spread beyond the place it started -- the pancreas.
Another good example of the importance of finding cancer early is melanoma skin cancer. It can be easy to remove if it has not grown deep into the skin. The 5-year survival rate (percentage of people who live at least 5 years after diagnosis) at this stage is nearly 100%. Once melanoma has spread to other parts of the body, the 5-year survival rate drops below 20%.
While colorectal cancer is often found after symptoms appear, most people with early colon or rectal cancer have no symptoms. Symptoms usually appear only with more advanced disease. This is why getting the screening tests before any symptoms develop is so important. Screening for colorectal cancer may find it at an earlier stage, when it is more likely to be curable. Screening tests can also help prevent cancer by finding polyps that can be removed before they become cancerous.
Early detection of lung cancer is critical for improving survival of this disease because only 15% of lung cancers are found when they are localized. Since there are few or no symptoms in the early stages of the disease, the majority of lung cancers are diagnosed in the late stages of the disease. Symptoms of later-stage disease may include a persistent cough, sputum streaked with blood, chest pain, voice change, and recurrent pneumonia or bronchitis. Treatment at early stages of cancer can lead to more treatment options, less invasive surgery, and a higher survival rate. For example, in recent years, the five-year survival rate of persons whose cancers were diagnosed when they were still localized (had not spread) was almost 50%. This drops to 2% for persons whose cancers were diagnosed after their cancers had spread distantly.
If prostate cancer is found during screening, it will likely be at an early, more treatable stage than if no screening were done.
Breast cancers that are found because they are causing symptoms tend to be larger and are more likely to have already spread beyond the breast. In contrast, breast cancers found during screening are more likely to be smaller and still confined to the breast. The size of a breast cancer and how far it has spread are some of the most important factors in predicting the prognosis (outlook) of a woman with this disease. Most doctors feel that early detection tests for breast cancer save many thousands of lives each year, and that many more lives could be saved if even more women and their health care providers took advantage of these tests.
Use of symptoms to trigger medical evaluation for ovarian cancer may not greatly increase early detection of ovarian cancer, and would result in a diagnosis of ovarian cancer in only 1 out of 100 women with symptoms. These results were published in the Journal of the National Cancer Institute (3). One of the reasons that ovarian cancer tends to be so deadly is that it is often detected at a late stage when it is difficult to treat. Therefore it is crucial to employ the effective screening tests that will allow for the earlier detection of ovarian cancer.
Treatment works best when cancer is found early. Finding cancer early usually means it can be treated while it is still small and is less likely to have spread to other parts of the body. This often means a better chance for a cure, especially if the cancer can be removed with surgery. The American Cancer Society and other health groups recommend cancer-related check-ups and certain tests for people even though they have no symptoms. This helps find certain cancers early, before symptoms start.

This article is brought to you by GenWay Biotech Inc. GenWay offers a cancer assessment aimed to detect 20 different types of cancer in the early stages under the brand name You Test You™, www.youtestyou.com.

References: All the data in this article are provided by the American Cancer Society.

1. American Cancer Society. 2010
2. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009
3. Cass I, Karlan BY. Ovarian cancer symptoms speak out—but what are they saying? Journal of the National Cancer Institute [early online publication]. January 28, 2010

Thursday, May 6, 2010

What are Cancer Clusters?

A cancer cluster is defined as a greater than expected number of cancer cases that occurs within a group of people, in a geographic area, or over a period of time. A cancer cluster is a statistical event, which may or may not have a cause other than chance. There are other cancer clusters that occur without any obvious source of carcinogens.
From 1961 to 1982, Centers for Disease Control and Prevention (CDC) investigated 108 reported cancer clusters in 29 states and 5 foreign countries (1). The studies were begun in hopes of identifying a viral cause of cancer clusters. During these investigations, however, no clear cause was determined for any of the reported clusters.
Cancer cluster investigations are complex and difficult for several reasons. Although any cancer case is one too many, suspected cancer clusters often do not contain enough cases for investigators to do a meaningful statistical analysis or reach a conclusion. Determining the cause of cancer is complicated because exposure to cancer-causing agents may have occurred many years before diagnosis. Therefore, assessing the amount and type of cancer-causing agents an individual has been exposed to is difficult. Unfortunately, cancer is often the result of a combination of agents and risk factors that interact in a way that science does not yet fully understand (2).
Below is the short list of cancer clusters in the United States that were thoroughly studied by epidemiologic investigations.
1963-1999, 56 people affected by lung cancer or mesothelioma in Libby, Montana. Suspected cause tremolite. (3).
1967-1973, 4 people affected by liver angiosarcoma in Louisville, Kentucky (4). Suspected cause vinyl chloride monomer (4).
1968-1995, 103 people affected by leukemia or lymphoma in Camp Lejeune, North Carolina. Suspected cause trichloroethylene (5).
1973-1982, 16-29 people affected by brain or CNS cancer in Cooke County, Texas. The cause is still unknown (6).
1979-1996, 40 people affected by brain or CNS cancer in Toms River, New Jersey. Suspected cause SAN trimer, styrene, acrylonitrile (7).
1981-1986, 21 people affected by leukemia in Woburn, Massachusetts, (21). Suspected cause: chloroform, tetrachloroethylene, trichloroethylene, 1,2-dichloroethene, arsenic (8).
1987-1999, 20 people affected by brain cancer, leukemia or lymphoma in Wilmington, Massachusetts. Suspected cause N-nitrosodimethylamine (9).
Two recent studies deserve more attention as they shed light on another factor that may be partially responsible for the occurrence of cancer clusters.
From 1997 to 2001, doctors in Churchill County found that 15 children had leukemia. This number was higher than usual. Beginning in 2002, the Nevada State Health Division and the Centers for Disease Control and Prevention (CDC) worked together to try to learn why so many children in Churchill County were getting sick. One test found that people who lived in Churchill County had higher amounts of two chemicals in their blood and urine than did people from other areas. The two chemicals were tungsten and arsenic. However, the higher amounts were found in children with leukemia and in children without leukemia (10, 11).
Another cluster was indentified in Sierra Vista, Arizona, where from 1995 to 2003, 11 children in were diagnosed with leukemia. Because this number of cases was higher than expected, the Arizona Department of Health Services and the Cochise County Health Department asked the Centers for Disease Control and Prevention (CDC) to help them try to learn why these children got sick. CDC’s National Center for Environmental Health tested blood and urine samples from some people in Sierra Vista to measure levels of chemicals in their bodies. The results of the study showed that levels of chemicals found in most study participants were lower than levels in the U.S. population. The levels of chemicals were not different between case and comparison families (12).
However, in both studies CDC scientists found a variation in a gene called SUOX. All of the children with leukemia had this variation in the SUOX gene, and almost half of the children who did not have leukemia had that same variation. This means that even if the variation in the SUOX gene adds to the risk for leukemia, it has to be noted that there must also be other factors involved. The direct cause of most leukemias still remains unknown, and scientists are still are not sure why so many children in both cancer clusters got leukemia (10, 11, 12).
Although no clear cause was reported for any of the cancer cluster, scientists documented 15 most commonly used environmental exposure terms found in articles pertaining to cancer clusters published in U.S. newspapers from 1977 to 2001 (13).



Disease clusters continue to concern the public, and public sentiment that environmental causes are responsible and must be investigated is widely prevalent. More than thirty years ago, the Centers for Disease Control and Prevention (CDC) recognized the need to develop operating procedures for response to public concern about disease clusters. In 1990 CDC released the “Guidelines for Investigating Clusters of Health Events” (14) in which a four-stage process was presented: a) an initial response to gather source information, b) an assessment of the occurrence of the health event, c) a feasibility study, and d) an epidemiologic investigation. During the last years, these guidelines have provided a framework that most state health departments have adopted, modifying it for their specific situations and available resources.
The states have the primary responsibility for response to cancer cluster concerns within their domain. State and local health departments respond to cancer cluster reports and inquiries about suspected clusters. Most state health departments’ strategies for cluster response are based on CDC’s “Guidelines for Investigating Clusters of Health Events” with some modifications. Usually, a local or state health department starts by gathering information about the suspected cancer cluster including expected cancer rate, types of cancer, number of cases, and the age, sex, race, address, occupation, and age at diagnosis of the individuals with cancer. Information may be verified by contacting patients and relatives or by obtaining medical records. This information is then compared to census data and state cancer registry data to determine if there is a higher than expected number of cases. Most investigations do not proceed beyond evaluation of the gathered information; however the local or state health department may perform a more intensive assessment or comprehensive epidemiological study. The decision to proceed to a more intensive investigation is usually based on a set of rules developed by the health department.
National Center for Environmental Health (NCEH) of CDC becomes involved when state health departments request assistance. NCEH response has ranged from consultation with appropriate staff to active participation in an epidemiologic or biosampling investigation. In some cases, NCEH has provided assistance by conducting analysis of biological samples and storing them for future study, as it did in the childhood leukemia clusters in Churchill County, Nevada and Sierra Vista, Arizona (11, 12).
This article is brought to you by GenWay Biotech Inc. GenWay offers a cancer assessment aimed to detect 20 different types of cancer in the early stages under the brand name You Test You™. To learn more, please visit the website www.youtestyou.com.

References:
1. Caldwell GG. Twenty-two years of cancer cluster investigations at the Centers for Disease Control. Am J Epidemiol 1990; 132[1]:S43-S47
2. CDC
3. McDonald, JC. Harris, J. Armstrong, B. (2004). Occupational and Environmental Medicine 61 (4), 363–366.
4. Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report. (Feb. 7, 1997). Epidemiologic Notes and Reports Angiosarcoma of the Liver Among Polyvinyl Chloride Workers -- Kentucky. 46 (5), 97–101.
5. US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry (ATSDR). (Jul. 2003). Survey of Childhood Cancers and Birth Defects at USMC Camp Lejeune. Retrieved Jan. 31, 2005
6. Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report. (August 24, 1984). Brain Cancer -- Texas 33 (33), 477–479.
7. New Jersey Department of Health and Senior Services, Hazardous Site Health Evaluation Program, Division of Epidemiology, Environmental and Occupational Health, & US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry (ATSDR). (Sep. 1997). Childhood Cancer Incidence Health Consultation: A Review and Analysis of Cancer Registry Data, 1979-1995 for Dover Township (Ocean County), New Jersey
8. Costas, K. Knorr, RS. Condon, SK. (Dec. 2, 2002). A case–control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water. Science of The Total Environment 300 (1-3), 23–35.
9. Massachusetts Department of Public Health. (2002). Wilmington Childhood Cancer Study. Bureau of Environmental Health Assessment. Retrieved Jan. 31, 2005.
10. National Center for Environmental Health, Centers for Disease Control and Prevention. (2004). Cancer Clusters - Churchill County (Fallon), Nevada Exposure Assessment. Retrieved Jan. 31, 2005.
11. http://www.cdc.gov/nceh/clusters/fallon/genetictesting.htm
12. http://www.cdc.gov/nceh/clusters/sierravista/default.htm
13. Beverly S. Kingsley, Karen L. Schmeichel, and Carol H. Rubin.: “An Update on Cancer Cluster Activities at the Centers for Disease Control and Prevention”, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Environmental Health Perspectives • VOLUME 115 | NUMBER 1 | January 2007

14. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001797.htm

Tuesday, May 4, 2010

Varying Survival Rates Based on Stage of Diagnosis

Survival rates are a way for doctors and patients to get a general idea of the outlook for people with a certain type and stage of cancer. Some people with cancer may want to know the survival rates for their type of cancer. Others may not find the numbers helpful, or may even not want to know them. It is up to the individual whether or not she/he wants to read about survival rates.
The 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is found at certain stage (I-IV). Of course, some patients live much longer than 5 years. Five-year relative survival rates for non-small cell lung cancer means that people who die of other causes are not included. A staging system is a standardized way in which the cancer care team describes the extent of the cancer. Below we present relative survival rates of non-small cell and small cell lung, colon, rectal, breast and prostate cancer.

The numbers on the Chart 1 are from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, based on people who were diagnosed with non-small cell lung cancer between 1988 and 2000.


*Stage IA is the earliest diagnosed stage and stage IV is the latest stage.

While these numbers provide an overall picture, keep in mind that every person's situation is unique and the statistics can't predict exactly what will happen in a certain case.

The numbers on the Chart 2 below are from the SEER database. They are based on people with small cell lung cancer between 1988 and 2001. Five-year relative survival rates (like the ones below) don't count people who died of other causes.



The numbers on the Chart 3 include people diagnosed with colon cancer who may have later died from other causes, such as heart disease. People with colon cancer tend to be older and may have other serious health conditions. This means the percentage of people surviving the colon cancer itself is likely to be higher, and many of them live much longer than 5 years.

Please note that in this study (Chart 3), survival was better for some stage IIIA than for some stage IIB. The reasons for this are not clear.



*Stage IA is the earliest diagnosed stage and stage IV is the latest stage.

In this study (Chart 4), survival was better for some stage III cancers than for some stage II cancers. The reasons for this are not clear.


*Stage IA is the earliest diagnosed stage and stage IV is the latest stage.

The numbers on Chart 5 are based on women treated a number of years ago.



The National Cancer Institute (NCI) keeps a database of survival statistics for different types of cancer. This database does not group prostate cancers by stage, but instead groups cancers into local, regional, and distant stages (Chart 6).
Local stage means that there is no sign that the cancer has spread outside of the prostate. This is like stages I and II. Almost 9 out of 10 prostate cancers are found in this early stage. If the cancer has spread from the prostate to nearby areas, it is called regional disease. This includes cancers that are stage III and the stage IV cancers that haven't spread to distant parts of the body. Distant stage includes the rest of the stage IV cancers -- all cancers that have spread to distant lymph nodes, bone, or other organs.



The 5-year relative survival rate is the percentage of men who do not die from prostate cancer within 5 years after the cancer is found. (Men with prostate cancer who die of other causes are not counted.) Of course, patients might live more than 5 years after diagnosis. These 5-year survival rates are based on men with prostate cancer first treated more than 5 years ago. Treatment has gotten better since then and for recently diagnosed patients this may result in a better outlook.

The following survival rates (Chart 7) are based on nearly 60,000 patients who were part of the 2008 AJCC Melanoma Staging Database. These are observed survival rates. They include some people diagnosed with melanoma who may have later died from other causes, such as heart disease. Therefore, the percentage of people surviving the melanoma itself may be higher.


*Stage IA is the earliest diagnosed stage and stage IV is the latest stage.

Other factors aside from stage may also affect survival. For example, stage for stage, older people generally have shorter survival times. The biggest drop begins at age 70. Although melanoma is uncommon among African Americans, when it does occur, survival times tend to be shorter than when it occurs in whites. Some studies have shown that melanoma is more serious if it occurs on a foot, palm, or nail bed. People with HIV infection and melanoma also are at greater risk of dying of their melanoma.

With recent advances in diagnostic, screening programs have more and more impact on increasing detection in earlier stages. For some types of cancer, screening can help find cancers in an early stage when they are more easily cured.
Prostate cancer can often be found early by testing the amount of prostate-specific antigen (PSA) in the blood. Another way to find prostate cancer is the digital rectal exam (DRE), in which a doctor puts a gloved finger into the rectum to feel the prostate gland. If prostate cancer is found during screening with the PSA test or DRE, cancer will likely be at an early, more treatable stage than if no screening were done. Since the use of early detection tests for prostate cancer became fairly common (about 1990), the prostate cancer death rate has dropped. Prostate cancer tends to be a slow growing cancer, so the effects of screening in these studies may become even more apparent in the coming years.

The goal of screening exams for breast cancer, such as mammograms, is to find cancers before they start to cause symptoms. Breast cancers that are found because they can be felt tend to be larger and are more likely to have already spread beyond the breast. In contrast, breast cancers found during screening exams are more likely to be small and still confined to the breast. The size of a breast cancer and how far it has spread are important factors in predicting the prognosis (survival outlook) for a woman with this disease. Most doctors feel that early detection tests for breast cancer save many thousands of lives each year, and that many more lives could be saved if even more women and their health care providers took advantage of these tests. Current evidence supporting mammograms is even stronger than in the past. In particular, recent evidence has confirmed that mammograms offer substantial benefit for women in their 40s. Women can feel confident about the benefits associated with regular mammograms for finding cancer early.

Colorectal cancer is a term used to refer to cancer that develops in the colon or the rectum. These cancers are sometimes referred to separately as colon cancer or rectal cancer, depending on where they start. In most people, colorectal cancers develop slowly over several years. Before a cancer develops, a growth of tissue or tumor usually begins as a non-cancerous polyp on the inner lining of the colon or rectum. A tumor is abnormal tissue and can be benign (not cancer) or malignant (cancer). A polyp is a benign, non-cancerous tumor. Some polyps can change into cancer, but not all do. From the time the first abnormal cells start to grow into polyps, it usually takes about 10 to 15 years for them to develop into colorectal cancer. Regular screening can, in many cases, prevent colorectal cancer altogether. This is because some polyps, or growths, can be found and removed before they have the chance to turn into cancer. Screening can also result in finding colorectal cancer early, when it is highly curable. If colorectal cancer does occur, early detection and treatment dramatically increase chances of survival.
The death rate (the number of deaths per 100,000 people per year) from colorectal cancer has been dropping for more than 20 years. There are a number of likely reasons for this. One is that polyps are being found by screening and removed before they can develop into cancers. Screening also allows more colorectal cancers to be found earlier, when the disease is easier to cure. In addition, treatment for colorectal cancer has improved over the last several years. As a result, there are now more than 1 million survivors of colorectal cancer in the United States. Regular colorectal cancer screening or testing is one of the most powerful weapons for preventing colorectal cancer.
The relative 5-year survival rate for colorectal cancer when diagnosed at an early stage before it has spread is about 90%. But only about 4 out of 10 colorectal cancers are found at that early stage. Once the cancer has spread to nearby organs or lymph nodes, the 5-year relative survival rate goes down, and if cancer has spread to distant organs (like the liver or lung) the rate is about 11%.
Not only does colorectal cancer screening save lives, but it also is cost effective. Studies have shown that the cost-effectiveness of colorectal screening is consistent with many other kinds of preventive services and is lower than some common interventions. It is much less expensive to remove a polyp during screening than to try to treat advanced colorectal cancer. With sharp cost increases possible as new treatments become standards of care, screening is likely to become even more cost effective.
Skin cancer is the most common of all cancer types. More than 1 million skin cancers are diagnosed each year in the United States. That's more than cancers of the prostate, breast, lung, colon, uterus, ovaries, and pancreas combined. The number of skin cancer cases has been going up over the past few decades. Finding possible skin cancers doesn't require any x-rays or blood tests -- just your eyes and a mirror. If skin cancer does develop, finding it early is the best way to ensure it can be treated effectively.
This article is brought to you by GenWay Biotech Inc. GenWay offers a cancer assessment aimed to detect 20 different types of cancer in the early stages under the brand name You Test You™. To learn more, please visit the website www.youtestyou.com.

References: All the data in this article are provided by the American Cancer Society.
American Cancer Society. 2010
American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009.

Tuesday, April 27, 2010

The Extreme Variance of Cancer Mortality Rates

The impact of cancer is difficult to measure. It requires a tremendous amount of effort to account for each individual case and further track the patient outcome. In the United States, we have many institutes which track the impact of cancer. This article focuses on key statistics provided by the National Cancer Institute (NCI) (http://statecancerprofiles.cancer.gov/). Some extreme variances of cancer mortality rates from the data provided in this article are:

• In California, Lake County has 89% more cancer deaths Mono County per capita;
• For lung cancer mortality in California, Lake County has 167% more deaths than San Benito County per capita;
• In the United States, Kentucky has 55% more cancer deaths than Utah per capita;
• For colorectal cancer in the United States, the District of Columbia has 77% more deaths than Utah per capita;
• For breast cancer in the United States, Alaska has 44% more deaths than Hawaii per capita.

The NCI 1of 27 Institutes and Centers that comprise the U.S. National Institutes of Health, which is part of the U.S. Department of Health and Human Services. NCI’s responsibilities include conducting and fostering cancer research; reviewing and approving grant-in-aid applications to support promising research projects on the causes, diagnosis, treatment, and prevention of cancer; collecting, analyzing, and disseminating the results of cancer research conducted in the United States and in other countries; and providing training and instruction in cancer diagnosis and treatment. In fulfilling its responsibilities, NCI has built a national network that includes regional and community cancer centers, physicians who are cancer specialists, cooperative groups of clinical researchers, and volunteer and community outreach groups (1).
Analysis of the data provided by the NCI shows the extreme variance of cancer mortality rates between sates and even between counties within the same sate (4). For instance in California, the lowest all-cancer death rate is observed in Mono County (Chart 1) and this rate is almost two times lower that the one observed in Lake County (Chart 2) (the highest all-cancer death rate in California).



*Numbers indicate annual number of deaths per 100,000 in the population.



*Numbers indicate annual number of deaths per 100,000 in the population.

Analysis of a relative contribution of different cancer types to the overall cancer-related deaths shows that lung cancer-related death primarily contributed to the observed differences. San Benito County (the lowest rate) has the lung/bronchus cancer rate that is almost 2.7 lower than the one observed in Lake County (Charts 3 and 4).



*Numbers indicate annual number of deaths per 100,000 in the population.



*Numbers indicate annual number of deaths per 100,000 in the population.

Other types of cancer also contributed to the extreme difference in cancer-related death rates in California but to the lesser extent. The lowest rate of deaths due to breast cancer in women has approximately 1.4 times difference with the highest rate (Calaveras County 19.6/100,000; and Lassen County 27.3/100,000). The lowest rate of death due to the prostate cancer has 1.9 times difference with the highest rate (Tuolumne County 18.1/100,000; and Sutter County 34.7/100,000).
Using extensive data collected and presented by NCI, we identified 10 states with the lowest and 10 states with the highest cancer mortality rates (Charts 5 and 6). Further analysis showed that lung cancer along with the prostate cancer appeared to be the major contributors to the extreme variance in cancer-related death. The lowest rate of deaths due to lung cancer has approximately 3.2 times difference with the highest rate (Utah 23.4/100,000; and Kentucky 74.8/100,000). The lowest rate of deaths due to prostate cancer has approximately 3.0 times difference with the highest rate (Hawaii 13.4/100,000; and District of Columbia 40.8/100,000).

*Numbers indicate annual number of deaths per 100,000 in the population.





Other types of cancer contributed to the lesser extent to the difference in cancer-related death rates. The lowest rate of death due to the colorectal cancer has 1.7 times difference with the highest rate (Utah 12.6/100,000; and District of Columbia 22.4/100,000). The lowest rate of deaths due to breast cancer in women has approximately 1.4 times difference with the highest rate (Hawaii 18.9/100,000; and Alaska 27.4/100,000).
Although the determinants of many geographic patterns remain to be elucidated, it is obvious that variations in cigarette smoking greatly influence the patterns of lung and certain other tobacco-related cancers. The report found that states with high rates of smoking also have high rates of tobacco-related cancers and overall cancer-related deaths. Comparing the state smoking rates (% of adults who smoke): Utah 9.3%; California 14%; Hawaii 15.4%; and West Virginia 26.5%; Kentucky 25.2%; Mississippi 22.7% (7), and the Charts 5 and 6 it becomes clear that states with the lowest smoking rates have the lowest cancer-related death rates and visa versa.
Obesity, physical inactivity, and poor nutrition are major risk factors for cancer, second only to tobacco use (8). Approximately one-third of the more than 500,000 cancer deaths in the US this year can be attributed to poor diet and physical inactivity, while another third is caused by use of tobacco products.
Early detection of cancer through screening has been shown to reduce mortality from cancers of the colon and rectum, breast, and uterine cervix (8). Screening refers to testing in individuals who are asymptomatic for a particular disease (i.e., they have no symptoms that may indicate the presence of disease). In addition to detecting cancer early, screening for colorectal or cervical cancers can identify and result in the removal of precancerous abnormalities, preventing cancer altogether.
This article is brought to you by GenWay Biotech Inc. GenWay offers a cancer assessment aimed to detect 20 different types of cancer in the early stages under the brand name You Test You™, www.youtestyou.com.










References:

1. National Cancer Institute.

2. The National Vital Statistics System.

3. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI).

4. National Cancer Institute: State Cancer Profiles (http://statecancerprofiles.cancer.gov).

5. Centers for Disease Control and Prevention: Cancer prevention and Control – Geographic Variations.

6. National Cancer Institute: Cancer Mortality Maps and Graphs.

7. Kaiser State Health Facts: 50 States Comparison (http://statehealthfacts.org).

8. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009.

The Relationship between Cancer and Smoking

The 1982 United States Surgeon General's report stated that "Cigarette smoking is the major single cause of cancer mortality in the United States." (1) This statement is as true today as it was then. Tobacco smoke contains over 4,000 chemical compounds. More than 60 of these are known or suspected to cause cancer. For example, about 90,000 men die of lung cancer each year in the U.S. About 78,700 lung cancer deaths among men are caused by smoking. This means that the smoking causes about 90% of lung cancer deaths among men (2). Statistics also shows that 80% of all lung cancer deaths in women are caused by smoking (2).
Lung cancer is not the only type of cancer that is linked with smoking. Cigarette smoking accounts for at least 30% of all cancer deaths. It is linked with an increased risk of the following cancers: lung, larynx (voice box), oral cavity (mouth, tongue, and lips), pharynx (throat), esophagus (tube connecting the throat to the stomach), stomach, pancreas, cervix, kidney, bladder, acute myeloid leukemia (3).
The effect of smoking on each type of cancer is different. For example, smoking greatly increases the risk of getting and of dying from cancers of the lungs and larynx (voice box). It has a smaller effect on cancer of the cervix.
Lung cancer is the leading cause of cancer death in both men and women, and is one of the hardest cancers to treat. It claims more than 150,000 lives each year (3). Smoking is responsible for almost 9 out of 10 lung cancer deaths. It increases the risk of getting lung cancer by the factors of 23 and 12 in men and women respectively (2). Lung cancer kills more people than cancers of the breast, prostate, colon and pancreas combined. There are tens of millions of current, former and secondhand smokers in the United States, all of whom are at high risk for lung cancer (3).
Former smoker or ex-smoker means someone who has smoked more than 100 cigarettes over his or her lifetime but does not now smoke every day or some days (2). Even decades after quit¬ting, the risk of lung cancer in former smokers is increased by the factors of 9 and 5 in men and women respectively (2). It has been shown that the risk of lung cancer in ex-smokers never returns to the rate seen in persons who have never smoked.
Even if a person never smoked he or she might have been exposed to secondhand smoke. It is a mixture of 2 forms of smoke that come from burning tobacco: sidestream smoke (smoke that comes from the end of a lighted cigarette, pipe, or cigar) and mainstream smoke (smoke that is exhaled by a smoker) (4).
Secondhand smoke is classified as a "known human carcinogen" (cancer-causing agent) by the U.S. Environmental Protection Agency (EPA), the U.S. National Toxicology Program, and the International Agency for Research on Cancer (IARC), a branch of the World Health Organization (5).
Scientific evidence indicates that there is no safe amount of secondhand smoke. Breathing even a little secondhand smoke is harmful to your health. The American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), the preeminent U.S. standard-setting body on ventilation issues, has concluded that ventilation technology cannot be relied on to completely control health risks from secondhand smoke exposure (5).
Non-smokers who breathe in secondhand smoke take in nicotine and other toxic chemicals just like smokers do. Secondhand smoke causes lung cancer in adults who don’t smoke. In the United States alone, each year it is responsible for about 3,400 lung cancer deaths in non-smoking adults (5). Breathing in secondhand smoke increases your chances of getting lung cancer by 20 percent to 30 percent. Moreover, concentrations of many cancer-causing and toxic chemicals are potentially higher in secondhand smoke than in the smoke inhaled by smokers.
Although no current screening guidelines for the lung cancer are established, the American Cancer Society recommends that people who are at increased risk for lung cancer, such as smokers, former smokers, or secondhand smokers, be aware of their lung cancer risk. They should talk to their doctors about their chances of getting lung cancer and the lung cancer screening (3).
Currently, when lung cancer is detected, the disease has already spread outside the lung in more than half of all cases. Most people with early lung cancer do not have any symptoms, so only a small number of lung cancers are found at an early stage. When lung cancer is found early, it is often because of tests that were being done for something else. Screening is the use of tests or exams to find a disease like cancer in people who don't have any symptoms. Because lung cancer often spreads beyond the lungs before it causes symptoms, a good screening test to find lung cancer early could save many lives (3). This means part of your health care should focus on related screening and preventive measures to help you stay as healthy as possible.
Several testing options could be available for pro-active people who are at increased risk for lung cancer:

Chest x-ray is the first test your doctor will do to look for any spots on the lungs. It is a plain x-ray of your chest. Studies have shown that this kind of screening does not find many lung cancers early enough to improve a person's chance for a cure (3, 6).
CT scan (computed tomography): A CT (or CAT) scan is a special kind of x-ray. Instead of taking just one picture, the CT scanner takes many pictures as it moves around you. A computer then combines these pictures into a picture of a slice of your body. Spiral CT can pick up tumors well under 1 centimeter in size, while chest x-rays detect tumors about one to two centimeters (0.4 to 0.8 inches) in size (3, 6).
MRI scan (magnetic resonance imaging): Like CT scans, MRI scans give detailed pictures of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI scans take longer than x-rays -- often up to an hour. MRI scans are useful in finding lung cancer that has spread to the brain or spinal cord (6).
PET scan (positron emission tomography): PET scans use a form of sugar that contains a radioactive atom. Cancer cells in the body absorb large amounts of the sugar. A special camera can then spot the radioactivity. This test can show whether the cancer has spread to the lymph nodes. PET scans are also useful when the doctor thinks the cancer has spread, but doesn't know where (6).
Tests of tissues and cells, such as lung biopsy or sputum cytology, can be used to follow up on imaging tests to be sure that something seen on an imaging test is really lung cancer. These tests are also used to decide the exact type of lung cancer and how far it may have spread (3, 6).
Screening blood tests are offered from the private sector to meet the needs of pro-active people who are at increased risk for lung cancer. It is up to the individual to be aware of their lung cancer risk by determining whether she/he belongs to one or more risk groups such as smokers, former smokers, or secondhand smokers and talk to his/her doctor to determine if screening tests should be implemented. If the health care provider does not cover screening tests which are preferred by the patient, other options are available from the private sector to address these needs at the patient’s own cost.
This article is brought to you by GenWay Biotech Inc. GenWay offers a cancer assessment aimed to detect 20 different types of cancer in the early stages under the brand name You Test You™.
References:
1. U.S. Department of Health and Human Services. The Health Consequences of Smoking – Cancer: A Report of the Surgeon General. Atlanta, GA: U.S, 1982
2. American Cancer Society (ACS), Smoking and Cancer Mortality Table: http://www.cancer.org/docroot/PED/content/PED_10_2X_Smoking_and_Cancer_Mortality_Table.asp
3. American Cancer Society (ACS), Detailed Guide: Lung Cancer.
4. U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta, GA, 2004.
5. U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, GA, 2007
6. American Cancer Society (ACS), Detailed Guide: Lung Cancer - How Is Lung Cancer Diagnosed?

Wednesday, April 7, 2010

Understanding The Role of the U.S. Preventive Services Task Force (USPSTF)

In November 2009, the U.S. Preventive Services Task Force (USPSTF) published new guidelines for breast cancer screening by mammograms which sparked controversy on a vital topic to cancer organizations worldwide, the importance of early cancer detection. These new guidelines are a significant shift from those issued in 2002, which at that time, recommended women ages 40 and older to have an annual mammogram. The new recommended ages by the USPSTF to screen women for breast cancer is now 50 and older, leading to many questions on why such a change in policy is necessary.
Immediately after this recommendation from the USPSTF, a statement from Otis W. Brawley, M.D., chief medical official of The American Cancer Society, stated, “The American Cancer Society continues to recommend annual screening using mammography and clinical breast examination for all women beginning at age 40….reasonable experts can look at the same data and reach different conclusions….the Society’s panel found convincing evidence that screening with mammography reduces breast cancer mortality in women ages 40-74…. With its new recommendations, the USPSTF is essentially telling women that mammography at age 40 to 49 saves lives; just not enough of them… The most recent data show us that approximately 17 percent of breast cancer deaths occurred in women who were diagnosed in their 40s.” According to the American Cancer Society’s cancer statistics, this 17% represents approximately 7,000 lives, which will be left at risk once these breast cancer screening policy changes take effect.
Additional support for breast cancer screening comes from researchers at the University of London, which conducted two studies looking into the risks and benefits of breast cancer screening. The first study predicted the number of women who would have died from breast cancer in Britain without screening. The second study evaluated the number of deaths among 80,000 Swedish women with access to screening programs. The results published in the Journal of Medical Screening showed that for every 28 breast cancer diagnoses between 2 and 2.5 lives were saved. The results from the Swedish study indicated that for every 350 women screened for 10 years for breast cancer, one life would be saved. This research, along with hundreds of other publications, indicates an opportunity for saving lives from further development and implementation of cancer screening.
As stated on the Agency for Healthcare Research and Quality’s website (www.ahrq.gov), the USPSTF mission is “to improve the safety, quality, efficiency, and effectiveness of health care for all Americans.” The recommendations of the USPSTF are considered to be the “gold standard” for clinical preventive services, and are followed by almost every major primary care and federal agency associated with health care. USPSTF recommendations are used in undergraduate and post-graduate medical and nursing education as a key reference for teaching preventive care.
So what is the reasoning behind the USPSTF’s breast cancer screening recommendation? False positives can lead to psychological distress, unnecessary imaging tests and biopsies in women without cancer, and inconvenience due to false-positive screening results. Radiation exposure, although a minor concern from mammograms, is also a consideration. The USPSTF recommends that physicians be required to consider additional factors, such as an individual’s personal risk of having cancer, before conducting screening procedures such as mammograms.
It is up to the individual and his/her doctor to determine if screening tests will be implemented. If the health care provider does not cover screening tests which are preferred by the patient, other options are available from the private sector to address these needs at the patient’s own cost.
This article is brought to you by GenWay Biotech Inc. GenWay offers a cancer assessment aimed to detect 20 different types of cancer in the early stages under the brand name You Test You™. To learn more, please visit the website www.youtestyou.com.

References:
1. Agency for Healthcare Research and Quality, Rockville, MD
2. American Cancer Society (ACS) American Cancer Society Responds to Changes to USPSTF Mammography Guidelines. http://www.cancer.org/docroot/MED/content/MED_2_1x_American_Cancer_Society_Responds_to_Changes_to_USPSTF_Mammography_Guidelines.asp
3. American Cancer Society (ACS) Cancer Statistics 2009. http://www.cancer.org/docroot/PRO/content/PRO_1_1_Cancer_Statistics_2009_Presentation.asp
4. Duffy, S., McCann, J., Godward, S., Gabe, R., Warwick, J. “Some issues in screening for breast and other cancers.” Journal of Medical Screening. 2006; 13(Suppl1): S28-S34
5. U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:716-26, W-236. [PMID: 19920272]

Tuesday, March 30, 2010

The Need of Early Detection to Fight Cancer

The Importance of Early Detection to Fight Cancer

This blog starts off a serious of articles called Fighting Cancer with Early Detection and is brought to you by GenWay Biotech Incorporated. Our mission is to provide our readers with important facts and figures to enable patients to make better health decisions. This article is not written by a doctor, and it should not be used in place of your physician’s recommendation. You may wish to use the information provided in this article to facilitate a discussion with your physician. To learn more about GenWay Biotech’s cancer assessment, visit the website www.youtestyou.com.

The impact of cancer in the United States in undeniable. Cancer directly affects about one in three women and one in two men in the U.S (1), with more than 560,000 dyeing (2, 3) from it each year. It is widely known that the best chance to reduce these fatality numbers is through early detection. There are two major components of early detection of cancer: screening and education to promote early diagnosis.

Regular use of established screening tests can prevent the development of cancer. Either through identification and removal or treatment abnormalities, screening tests can improve survival and decrease mortality by detecting cancer at an early stage when treatment is more effective. It is important to note that screening refers to testing in individuals who have no symptoms for a particular disease) (4). This makes sense because in many cases symptoms are not present before cancer is diagnosed.

Early detection of cancer through regular screening has been shown to reduce the number of deaths from cancers of the colon and rectum, breast, and uterine cervix. For instance, in addition to detecting cancer early, regular screening can, in many cases, prevent colorectal cancer altogether. This is because some polyps, or growths, can be found and removed before they have the chance to turn into cancer (4).

Survival rates improve dramatically when cancer is diagnosed early and the disease is confined to the organ of origin. The relative 5-year survival rate for colorectal cancer when diagnosed at an early stage before it has spread is about 90%. But only about 4 out of 10 colorectal cancers are found at that early stage. Once the cancer has spread to nearby organs or lymph nodes, the 5-year relative survival rate goes down, and if cancer has spread to distant organs (like the liver or lung) the rate is about 11% (4).

A standard 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed; it includes people with colorectal cancer who may die of other causes, such as heart disease. Five-year relative survival rates are adjusted for patients dying of other diseases, so they reflect the chances of not dying specifically from colorectal cancer. (ACS)

Another striking example is the fact that nine out of 10 women can survive breast cancer simply by detecting it early. Prognosis of a breast cancer depends largely upon its stage and grade at diagnosis, 5-year survival rates ranging from 84% in women diagnosed with Stage 1 disease to 18% in women with Stage 4 disease.

Education to promote early diagnosis should encompass the increased awareness of new screening tests and possible warning signs of cancer, among physicians, nurses and other health care providers as well as among the general public. People without symptoms or special risks need to be aware of these screening methodologies and to be sure they are communicated to the physician.

National organizations such as American Cancer Society (ACS), National Cancer Institute (NCI), American Society of Clinical Oncology (ASCO) and American Academy of Family Physicians (AAFP) are dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer through research, education, advocacy, and service. A table below represents the generally accepted screening methods based on cancer type for your reference.

This vlog is brought to you by GenWay Biotech Incorporated. Our company strongly believes in the importance of early cancer detection and we commercialize cancer assessment aimed to detect cancer in the early stages under the brand name You Test You™. To learn more please visit the website www.youtestyou.com.

References:

1. Horner MJ, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP, Stinchcomb DG, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site, 2009.

2. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 2004 Incidence and Mortality. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, 2007.

3. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009.

4. American Cancer Society. Cancer Prevention and Early Detection Facts and Figures 2009. American Cancer Society, 2009.