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  GENETIC TESTING The majority of cancers are "sporadic." This means they are the result of environmental exposures or possible random events within a cell. Therefore, these cancers are genetic, however they are not hereditary. Familial and hereditary cancers are thought to consist of 35% of all colorectal cancers and a significant portion of other cancers. A familial cancer is a hereditary cancer that may be due to shared environmental or lifestyle factors. Hereditary cancers, such as Lynch syndrome, result from an inherited gene mutation or variant that is present in every cell and can be passed onto the children. Lynch syndrome is the result of a mutated gene. To make sense of this, we need to think of the composition of our bodies, which are made of millions of cells. Each of these cells has 23 pairs of chromosomes and within the chromosomes are genes. These genes are lined up on the chromosomes in a very specific manner. When a gene is not normal or when some chromosomes are forgotten or duplicated, defects in the body or within its system can occur, some of which can be mild defects or some as serious as Lynch syndrome. In those of us who have Lynch syndrome, a gene stopped working that usually works to prevent colon, endometrial and other Lynch cancers. Therefore, the cancers are likely to develop...and at a younger age. There are four common basic mutations known to date, including MLH1, MSH2, MSH6 and PMS2, as well as EPCAM and a few lesser known. These genes are involved in repairing mistakes in DNA which may occur when the cell goes through the division process. Mistakes in DNA can occur due to environmental factors (i.e., exposure to chemicals, drinking impure water, etc.) however environmental mistakes do not ordinarily create inherited cancers. Epcam deletions can create Lynch syndrome. The EPCAM gene is a recently discovered contributor to Lynch syndrome, accounting for an estimated 1-3% of all detectable Lynch syndrome mutations. Studies indicate that large deletions in the end of this gene can lead to a loss of MSH2 expression and result in Lynch syndrome. With the exception of the environmental mutations and one percent of those with Lynch syndrome possessing what is known as a "de novo" mutation (meaning new and not known previously in which no known family members have/had Lynch syndrome), all other mutations are hereditary and are created by germline mutations, or rather those created during the reproduction process (in the egg or in the sperm.) Lynch syndrome cancers are extremely aggressive and don't have the extended "dwell time" (time tumors live and exist in the body until becoming cancerous) as other cancers, thus the reason it is very important to obtain regular surveillance testing. Currently, there is no gene therapy, which is commonly referred to as a "cure" for Lynch syndrome, however researchers are working feverishly in an attempt to find a way to neutralize the "rogue genes." Technology is being explored which will work sort of like an automobile gas pedal...as the gas is pressed which creates the acceleration of the cancer formation, the brake is pressed at the same time, so the vehicle will not move forward or backward. Of course, this technology, if possible, is many years away and in the absence of a cure, the closest thing to a cure is genetic testing. Genetic testing is essential toward survival. With diagnosis, individuals can obtain yearly surveillance testing during which time if pre-cancerous or cancerous polyps are discovered, they can easily be removed at an early stage-- when treatment is most effective. Without early prevention, individuals develop cancers at an aggressive rate and with metastases, survival becomes more difficult. A genetic test is ordinarily taken from a standard blood or saliva sample, which is processed within a clinical laboratory. A positive result for Lynch syndrome (HNPCC) makes one a "mutation carrier" and not only diagnoses an individual with Lynch syndrome but also serves as verification of having an increased risk for cancer. That risk is then monitored by one's health provider with surveillance measures and an annual testing regiment.     If there is a mutation which has previously been identified within the family and the test result of that specific mutation comes out negative, then it is determined one has no increased cancer risk and the individual does not have a mutated gene. Any and all cancer screening will be based upon the same screening given the general public. If a mutation has not been previously identified in the family and a comprehensive panel has not identified a mutation, then it is determined that a cancer risk is not fully defined and is unknown. As a result, based on the personal and family history of cancer, medical management for screening and surveillance will be determined. Most individuals who are diagnosed with Lynch syndrome, by genetic testing, sing praises as to the benefits. Not only are they monitored closely by medical professionals, their families also have an opportunity to be protected and to live longer lives. Psychologically and emotionally, changes occur within those who test positively. The "unknown family cancer thing" suddenly has a name and there is hope and empowerment in being able to control it. The wait is over and stress and anxiety is relieved. For some, it is a relief. For others, it is bittersweet. And for some, testing does have its limitations and isn't perfect. Not all causes of hereditary cancer can be detected and though a negative result is extremely helpful when there is a known mutation in the family (thus being a true negative,) there is always the fear the negative may not truly mean "negative" in the absence of a family mutation. In that case, the uncertainty will continue to exist, however if one meets the criteria for Lynch syndrome, they can and should receive annual screenings for cancer, the same as an individual who has been diagnosed with a known mutation. Finally, testing has not fully evolved and there are other genes out there that have yet to be discovered, as well as variants continuing to be discovered. So, dependent upon your family history, your needs and understanding of genetic testing, its important to speak with your genetic counselor and your health care provider to determine if testing is good for you and for your family.     According to the National Cancer Institute, general population studies have indicated the majority of individuals, internationally, are not adverse to genetic testing for hereditary cancers but more concerned as to whether or not treatment for the hereditary condition would be available. For resources where to obtain low cost or no cost treatment for those without insurance, view the link marked "Support" to your left and scroll down to the country or state in which you reside. Study results also indicate a primary motivation for individuals submitting to genetic testing is a concern and a desire to provide protection for their children and loved ones, as well as the ability to reasonably determine for themselves what could occur in the future-- in order to make decisions as whether or not to bear children, engage in certain occupations, determine where to reside and in making other major lifestyle choices. With enhanced surveillance and known successful treatment methods, hope has never been greater than it is today, for individuals with Lynch syndrome and with genetic testing, individuals have all the tools they need for an enhanced quality of life. To learn more about whether or not one is at risk, MD Anderson has an excellent overview available.   MSI/IHC TESTING The microsatellite instability (MSI) test and the IHC test are pathology procedures performed upon the tissue of a colorectal or endometrial tumor, from an individual who has already contracted cancer. These tests are conducted to determine if the tumor has specific characteristics known to Lynch syndrome tumors and can identify specific genes which may suggest the possibility of Lynch syndrome. Genetic testing is then recommended if a possibility of the existence of the Lynch syndrome occurs. Several top research institutions in the United States have determined pathological testing of colon cancer tumors to be cost effective. There are many institutions testing every colon tumor with the above testing process. Many experts recommend this process and there are many that also recommend the testing of all endometrial cancer tumors, as well.   QUICK FACTS Approximately 10% of all cancers are hereditary. Approximately 145,000 people per year get colon cancer and approximately one in every 35, have Lynch syndrome. It is estimated by Johns Hopkins that 600,000 individuals, within the United States, are projected to have Lynch syndrome, however less than 5% of that number have been diagnosed. Other institutions estimate the number of those thought to be affected to be much higher. The only true form of diagnosis of Lynch syndrome is through genetic testing. Genetic testing saves lives.   LYNCH CANCERS LIFETIME RISK Colon Cancer - Up to 80% General Population 2% Endometrial Cancer - Up to 60% General Population 1% Stomach - Up to 13% General Population - 1% Ovarian - Up to 12% General Population 1% Those diagnosed with Lynch syndrome have a slightly elevated risk over the general population of developing cancers of the kidney/urinary tract, brain, small intestine, cervix, liver, bladder, ureter, esophagus, small bowel, pancreas, hepatobiliary tract, prostate, gall bladder duct, may contract sebaceous adenomas (skin cancers - Muir Torre) and cancer of the brain. There are also lessor known cancers which have been discovered during research studies and thought to be as a result of the Lynch syndrome, such as sarcomas, adrenal gland tumors, thyroid tumors and other cancers.  Certain subsets of Lynch syndrome are known to present a high risk of breast cancer to individuals. If your family has a history of these cancers, be certain to document the specifics and speak with your physician.   THE GENETIC COUNSELOR The genetic counselor plays an important role in the lives of those with Lynch syndrome. Having considerable education and knowledge of genetic conditions, they can provide us with an explanation of how and why we are at risk for Lynch syndrome as well as provide information on risk to our families. Genetics is complicated and with a syndrome that possesses over 1100 variants, as Lynch syndrome, it is important to provide your physician with all the information you can find on your family history. The physician will assess it and most likely refer you to a genetic counselor. Genetic counselors are few and far between and there are far too many of them for the numbers of individuals who are now being screened for genetic conditions. Advocacy needs to stand up and encourage public awareness of the occupation and recruitment into schools that offer a Masters program in genetic counseling. As well, advocacy needs to lobby for financial assistance to obtain more genetic counselors so individuals can take advantage of the opportunities and benefits they offer. Finding a genetic counselor in small states or rural areas may be difficult. In that situation, hopefully, the physician will take advantage of the services which are offered by the many excellent genetic counselors offered as a service by commercial testing laboratories or refer the patient to the services of telephonic genetic counseling. If you have difficulty finding a genetic counselor who can provide services within a reasonable amount of time, please call us at 707-689-5089 and we will be more than happy to assist with attempting to find effective, timely, genetic testing services. However, bottom line is genetic counseling should be a choice of the individual and not a requirement of the insurance company or the health institution which is administering the test.  No person should be required to attend a separate session, as a percursor appointment to obtain a test which can detect a life threatening condition.  Rather than ignore mandatory attendance with genetic counseling and forego genetic testing, give us a call and let us know so we may be able to assist in finding alternative methods of testing which may be within your own realm of comfort.   Genetic testing provides us with the knowledge to make effective decisions for ourselves and our families in the future. Knowledge is power. If we know we are at high risk for for a myriad of cancers, which may very well adversely affect us and our children in the future, we have the ability to attempt to protect ourselves.     HOW TO LOCATE A GENETIC COUNSELOR: National Society of Genetic Counselors GeneClinics American Society of Human Genetics Genetic Alliance   Modified 5/24/2013
Monday, 15 February 2010 | 32185 hits
    Glossary   Adenoma- A benign polyp that may be pre cancerous.   AmsterdamCriteria:  Guidelines to determine who should be referred for Lynch syndrome genetic testing.   Anus- Outlet of the rectum.   At risk- A person at risk has the possibility of having Lynch syndrome due to family history, however has not been tested.   Autosomal dominant- A pattern of inheritance in which an affected individual has one copy of a mutant gene and one normal gene on a pair of chromosomes.  Individuals with autosomal dominant diseases have a 50-50 chance of passing the mutant gene and therefore the disorder onto each of their children.   Barium enema- Chalky liquid, resistant to x-rays, inserted into the large intestine which allows the operator to view the interior of the bowel and detect anything unusual.   Base Pair - two nucleotides on opposite complementary DNA or RNA strands which  are connected via hydrogen bonds (the center matter connecting each strand of a double helix together into one strand.)   Benign- Not cancerous   Bethesda Criteria:  Guidelines to determine who should submit to Lynch syndrome genetic testing and MSI testing.   Biopsy- Removal of tissue for examination under a microscope.   CA-125 - A blood test that assesses the concentration of CA-125, an antigen found in ovarian cancer.   CAT scan- (Computerized Axial Tomography) - a form of x-ray that shows the size and shape of body organs layer by layer.   Cecum- The first section of the large intestine (colon).   Chemotherapy Neuropathy - nerve damage primarily in the hands, feet, arms and legs, resulting from chemotherapy.   Chromosome- Contains the genetic material of a cell (genes). The normal number of chromosomes in a human cell is 46 (23 pairs).   CIPN:Chemotherapy Induced Peripheral Neuropathy  (See Chemotherapy Neuropathy)   Codon:  Three adjacent bases on a DNA molecule determines the position of a specific amino acid protein molecule during protein synthesis.   Colectomy- The surgical removal of the colon (large intestine). Colon - (Large intestine, large bowel), About five to six feet long, it comprises the last section of the colon and includes the cecum, ascending colon, transverse colon, descending colon and sigmoid colon.   Colonoscopy-  Also known as "scope," it is an examination of the inside of the entire colon by use of a  flexible tube, about five feet in length.  The tube has a light source, a magnifying eye glass and an open channel through which air can be passed and biopsies can be taken.   DNA- (Deoxyribonucleic Acid). The molecule that contains the code for the genetic blueprint. It is found in the nucleus of cells. Duodenum - The first part of the small intestine, about twelve to fifteen inches long.   Endometrial Aspirate - Extraction of tissue from the uterine lining, by suction, for examination.   Endometrium- The mucousy membrane composing the inner layer of the uterine wall.   Epcam Deletion:  On chromosome 2, the EPCAM gene lies next to the MSH2 gene. Each gene provides instructions for making protein.  The EPCAM gene causes the MSH2 gene to be turned off, by a mechanism called promoter hypermethylation. It causes too many methyl groups to be attached in the promoter region and they attach to the MSH2 gene, resulting in less protein produced in epithelial cells. Loss of this protein results in loss of DNA repair.     Esophagogastroduodenoscopy (EGD, Upper Endoscopy)- Examination by use of a flexible tube passed through the interior of the upper GI tract (esophagus, stomach, and duodenum). The tube has a light source, a magnifying eye glass, and an open channel through which a biopsy can be taken.   ET- Enterostomal Therapist; a specialist, often a nurse, who assists individuals who wear an external abdominal appliance to collect body waste.   Familial Cancer -   Cancer that occurs in families more often than would be expected by chance. These cancers often occur at an early age, and may indicate the presence of a gene mutation that increases the risk of cancer. They may also be a sign of shared environmental or lifestyle factors.   FAP (Familial adenomatous polyposis)- An inherited disorder of the gastrointestinal tract in which there are 100 or more pre cancerous polyps.   Flexible sigmoidoscopy- A test in which a flexible tube about 2 1/2 feet in length is used to examine the rectum and lower part of the large bowel. The tube has a light source, a magnifying eyepiece, and an open channel through which air can be passed and a biopsy taken.   FOBT Test: Fecal Occult Blood Test is a non-invasive "at home" test, used to detect hidden blood in the stool and often utilized for colon cancer screening.   Gastroenterologist - A physician who specializes in the gastrointestinal tract.   GI (gastrointestinal) tract- Consists of the esophagus, stomach, small intestine (22-25 feet in length), and large intestine (5-6 feet in length).   Gene- A basic unit of heredity with each occupying a certain, specific place on a chromosome.   Genetic Testing - A blood test assessed by a lab to determine if certain Lynch syndrome mutations exist.   Geneticist-  A physician who specializes in genetics.   Germline Mutation- Same as hereditary mutation, called germline because hereditary mutations come egg and sperm cells, which are also called germ cells.   Glioblastoma- A type of primary malignant brain tumor sometimes associated with Lynch syndrome.   Gynecolgist- A physician that specializes in women's cancers.   Hemoccult test- A test using specially treated cardboard slides to check for hidden blood in the stool.   Hereditary- Genetically transmitted from parent to children.   hMLH1, hMSH2, hPMS1, hPMS2- The abbreviated names of some of the more known genes that, when abnormal, cause HNPCC. They are located on chromosomes 2, 3, and 7.   HNPCC(Hereditary Nonpolyposis Colorectal Cancer) -  The name of a genetic condition which encompasses Lynch syndrome AND Familial Colorectal Cancer Type X, a familial hereditary cancer condition.   Hysterectomy- Surgical removal of the uterus.   IHC Testing - (See Immunohistochemistry)   Ileoanal pull-through (pelvic pouch procedure, ileoanal anastomosis procedure)- Removal of  the colon and the lining of the rectum, leaving the underlying anal muscles, or sphincters. The last part of the small intestine is joined to the anus and an internal pelvic pouch is created.   Ileorectal anastomosis- Removal of the colon and joining of the last part of the small intestine (ileum) to the rectum.   Ileostomy (proctocolectomy)- Removal of the colon, rectum, and anus. An opening is then made from the ileum through the abdominal wall.   Ileum- The last part of the small intestine, 12-15 feet long.   Immunohistochemistry- Also known as IHC.  Pathology test of tumor involving staining tumor tissue samples to determine the presence or the absence of certain proteins which may reveal which mutated genes caused the cancer.   Inflammation - Chronic inflammation can trigger the immune system to battle against a persistent infection or bacterium and can contribute to the development of cancer.   Jejunum- The middle part of the small intestine, 8-10 feet long.   Karyotype- A picture of the chromosomes.   Keratoacanthoma- False skin cancer, appearing like a little volcano   LSI- Abbreviation for Lynch Syndrome International   Lynch Syndrome I & II- Another name for the inherited condition, HNPCC.   Malignant - Cancerous   Marker- A physical abnormality that may indicate the presence of, or may predict the future occurrence of a specific disorder in an individual.   Metastasis- Spread of cancer by the lymphatics or bloodstream to other sites in the body.   Microsatellite: Strand of DNA consisting of a sequence of repetitions of one to six base pairs in length.   Microsatellite Instability -  Condition created by damaged DNA due to defects in the normal DNA repair process.   MisMatch Repair Gene - Genes that contain mismatch repair proteins that check for and repair mistakes made in the production of new DNA.  When a mismatch repair gene becomes altered, as in Lynch syndrome, it ceases to make proteins or ceases to work properly, allowing cancers to develop.   Missense Mutation:  A missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. This can render the resulting protein nonfunctional.   MMR- Mismatch Repair   MRI- A procedure in which radio waves and a powerful magnet linked to a computer is used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue.   MSI- Pathology test of a tumor to determine if instability or other qualities of Lynch syndrome exist.   Muir Torre - A rare inherited skin disorder associated with mutations in mismatch repair proteins, hMSH-2 and hMLH-1, which predispose affected patients to cancer malignancies.   Mutation- A change in a gene which may result in a specific disorder.   Non-Invasive-  A procedure in which nothing enters the body (i.e., saliva DNA testing)   Nonsense Mutation: a genetic mutation in a DNA sequence that results in a shorter, unfinished protein product which occurs when a premature nonsense or stop codon is introduced into the DNA sequence. When it is translated into protein, the protein is incomplete short of the normal therefore, most of these mutations resulted in nonfunctional proteins.   Oncologist – A physician who specializes in treating cancers   Ostomate- A person with an ileostomy (or colostomy).   Palliative Care - Medical or comfort care that reduces the severity of a disease or slows its progress rather than providing a cure, i.e.,  if surgery cannot be performed to remove a tumor, radiation treatment might be tried to reduce its rate of growth, and pain management could help the patient manage physical symptoms.   Pathologist: A physician who examines tissues and fluids to diagnose disease to assist in making treatment decisions   Pedigree- family tree; genealogy.   Polyp- nonmalignant growth of tissue protruding from the mucous lining of an organ such as the nose, bladder, or intestine. Also called polypus   Polyposis- See FAP above.   Port - implanted device, below the skin, allowing a catheter to be attached to infuse medicines and fluids such as chemotherapy into the body and to allow blood to be drawn out.   Previvor- An individual diagnosed with Lynch syndrome but whom has not contracted a cancer.   Primary Brain Tumor -   tumor that originates in the brain or spinal cord tissue rather than spreading to the brain from another part of the body.   Proband:  First individual identified in a family that has a specific hereditary disorder.   Prophylactic:  A preventative measure   Propositus/Proposita- (Proband; Index case). The first individual to be identified in a family that has a specific hereditary disorder.   Sarcoma - tumor of the soft tissue or bone   Sebaceous Adenomas- Non cancerous skin tumor of an oil producing gland   Sebaceous Carcinoma - Cancerous skin tumor of an oil producing gland   Sebaceous Epithelioma - A benign tumor of the epitheliom of the sebaceous gland containing basal or germinal cells.     Salpingo-oophorectomy- Removal of the ovary and its Fallopian tube.   Sporadic Cancer:  Cancer occurring in people with no family history and no inherited cause.   Staging- Levels of cancer advancement in the body.   Stoma- Artificially created opening in the abdomen.   Surveillance - Regularly scheduled tests to detect cancer   Survivor- Individual diagnosed with Lynch cancer and has contracted a Lynchcancer.   Syndrome- A collection of abnormal physical characteristics occurring in an individual   Transvaginal Ultrasound - High-resolution images of the uterus and ovaries; may be used to screen for endometrial or ovarian cancer   Urine Cytology - Examination of the urine to detect cancer and inflammatory disease in the urinary tract.   Urologist- A physician who specializes in the urinary tract.   VUS - A variant of uncertain significance (VUS) is a genetic sequence change which association with hereditary risk is currently unknown.  Persons with a VUS should be managed as though they have Lynch syndrome.    
Saturday, 16 February 2013 | 2722 hits

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