Genetic Testing for Cancer
Genetic Testing for Cancer plays vital role in diagnosing cancer. Approximately 5 to 10 percent of developed cancers are cause by inherit genetic variants of specific genes. Genetic mutations play a vital role in all cancers. Investigators have associated mutations in specific genes with more than 50 hereditary cancer syndromes, which are disorders that make individuals susceptible to developing specific cancers. Specific genetic factors done via genetic testing for cancer, together with environmental cues, medical history, and lifestyle habits may interact in different ways to produce a particular type of cancer.
(Image Credits – shutterstock.com)
Mutations in a unique category of genes give rise to cancer. These genes are called proto-oncogenes, many of which regulate cell division. Thus when these genes are mutated, the cells enter a state of uncontrolled division, resulting in an abnormal cluster of layers of cells called a tumor. We shall look at some examples of oncogenes later in this chapter.
What is genetic testing?
Genetic tests reveal whether a family member with a disease has one of the known mutations linked to that particular disease. This test result allows screening of other family members who are not yet showing any symptoms of the disease to be check to see if they have inherit the same mutation. This practice is typical for a family member who carries a cancer-associated mutation so that when screening of other family members happens to be positive, they will be consider as genetic-high-risk. This allows them to be monitor through medical examinations, various diagnostic tests and preventive measures to avoid the possibility of developing the disease.
What is the procedure for genetic testing?
(Image Credits – shutterstock.com)
Your doctor will order genetic testing based on your family history and sometimes your medical history that suggest that you are at high risk for particular cancer.
- A small sample of your body fluid or cells is obtained for initial testing.
- The sample is then taken to a genetic testing lab.
- The lab will perform tests to identify changes in the chromosomes or genetic mutations.
- The lab can also determine changes in protein levels and tell abnormal from what is normal.
- The testing lab will prepare a report of your results and send it to your doctor who ordered the test or a genetic counselor. It takes about 2 weeks to get your result.
- The result is presented as one of the following; a) positive, b) negative c) a variant of unknown significance was identified, or d) a benign (non-cancerous) polymorphism or variant was unidentified.
- Your doctor or the counselor will explain the meaning of your results to you.
- Know that your results can be assessed by your other health professionals.
- If your result is positive, then it is illegal for it to be used against you.
What types of genes are associate with various cancers?
The wild-type or normal versions of genes associated with cancer are called proto-oncogenes. Their name came about by the fact that under healthy conditions, they are normal genes that are express to regulate cell growth and division. However, if for some reason mutations in their DNA sequence occur, they can become oncogenes, which means that they had lost their cell regulatory potential, making the cells in that area of the body overgrow without control.
Family medical history information has enabled researchers and doctors to identify people who have an increased risk of certain cancers. Once a patient fills out a family medical history and their lifestyle paperwork at the Doctor’s Office, the doctor uses the information and may order imaging tests and/or DNA analysis using a drawn blood, cheek or skin cells for testing. To confirm their findings as to whether you have cancer or not, a biopsy will have to be obtain from the suspicious site for testing. The following genes have been map to be associate with different types of cancers:
Breast cancer type 1 and 2 susceptibility proteins (BRCA1 and BRCA2) are express in breasts. All women have the BRCA1 and BRCA2 genes. In healthy individuals, they suppress the formation of tumors by helping with the regulation of cell division, that is, they interact with other proteins to keep cells from growing and dividing too rapidly. They also act in concert with other proteins to repair damaged DNA, thereby, securing the cell’s genetic material. Unfortunately, BRCA genes, identified on chromosome 17 and chromosome 13 respectively, have unusually high densities of repetitive elements or regulatory DNA sequences which contribute to making their chromosome very unstable and thus generate a number of genetic variants, the majority of which have cancer developing susceptibility.
In short, the abnormal variants can be inherited in certain families. According to the Centers for Disease Control and Prevention, approximately 1 in every 500 women in the USA has a mutation in either her BRCA1 or BRCA2 gene and there is 50% chance of inheriting the mutant gene from your mother or father who has it. It has been predict that approximately 55-65% of women who inherit the susceptible BRCA1 or BRCA2 variant genes will develop breast cancer by the time they approach the age of 70 years. In general, the same hereditary pattern applies to all the cancer susceptibility genes, as shown in the picture.
BRCA1 and BRCA2 gene mutations are most popularly linked to breast cancer, but they are also associate with ovarian, prostate and pancreatic cancers.
Phosphatase and tensin homolog (PTEN) gene expresses an enzyme which acts as a tumor suppressor. Individuals that inherit a mutant version of the gene are susceptible to breast, liver, and uterine cancers.
Tumor protein p53 (TP53), when expressed as protein, suppresses tumor growth. Thus when a mutation occurs in the gene, the cell growth suppression is lost and cancer then develops. The gene is associate with breast, brain, bone, leukemia, adrenal glands cancers.
MSH2, MLH1, PMS2 and EPCAM genes
MSH2, MLH1, MSH6, and PMS2 are DNA mismatch-repair genes and inheritable mutations in these genes can result in individuals with genetic variants of high-risk susceptibility of colorectal, uterine lining (endometrial), ovarian, stomach, brain, pancreas and small intestinal cancers. The EPCAM expresses a protein known as an epithelial cellular adhesion molecule (EPCAM), a protein present in epithelial cells. These are cells that serve as lining surfaces and cavities of tissues and organs of the body. Studies have shown that certain deletion mutations of the EPCAM gene can cause Lynch syndrome (a hereditary disorder that increases the likelihood of developing colon cancer) by preventing MSH2 expression in tissues and organs of the body that make these vital proteins. Likewise, mutations in the PMS2 gene can cause Turcot’s syndrome (an inheritable disorder which increases the likelihood of developing colorectal cancer).
The Adenomatous polyposis coli (APC) gene is a tumor suppressor gene that modulates cell growth and division (the cell cycle). Generally, mutations in this gene can result in dysregulation of the signaling systems that make sure cell growth and division are properly control. APC dysfunction has been associate with colorectal, brain, small intestine, skin and bone cancers and also non-cancer growths like polyps.
Normal retinoblastoma (RB1) gene expresses a tumor suppressor protein that prevents cells from overgrowing by modulating cell growth and division. In several cancers, typically, bone, skin and endocrine gland, mutations are found in the RB1 gene which renders it dysfunctional, thereby, bringing about uncontrollable cell cycle which might lead to cancer. Endocrine glands are like sacs that make hormones and secrete their content directly into the bloodstream. For example, pineal gland (a gland that produces sleep and wake control hormone called melatonin), adrenal gland, thyroid and parathyroid glands.
The RET gene is a proto-oncogene which expresses a receptor tyrosine kinase. In healthy cells, RET plays an essential role in the development of several types of nerve cells, including intestinal neurons and involuntary nervous system functions . RET expressed protein partner with several genes, such as the ALK and ROS1 protein tyrosine kinases. By and large, mutations in the RET gene have been associate with lung, thyroid, and abdominal cancers.
E6 and E7 genes
Meanwhile, researchers have not identified any genetic factors that contribute to the development of cervical cancer. However, studies have shown that human papilla virus (HPV) infection, known to cause cervical cancer brings about some genetic implications. HPV causes the production of 2 proteins known as E6 and E7 which silence some tumor suppressor genes. It is possible that the resultant lack of suppression may allow the cervical lining cells to overgrow and develop changes that may lead to cervical cancer.
What are the benefits of genetic testing for cancer?
Your doctor will order a genetic testing for you because your medical or family history suggests you are at high risk for particular cancer. Surely, you will benefit from the testing results as follows:
- You will get to know whether you are positive for a susceptible gene or not and set your mind at rest if the result is negative.
- If the result is positive, then there is the likelihood of you having particular cancer, your doctors will help in guiding your future risks in getting the disease through necessary preventive measures.
- If your test is positive, then you will have genetic counseling sessions to help you to deal with it and take on a new lifestyle.
- Your test results can be a valuable asset to other family members, in that they will also get test and if any of them get positive results they will be help with counseling and treatment measures.
- In general, it can be use as a diagnostic tool to confirm the genetic basis of your cancer and design treatment strategies unique for your case.
What are the pros and cons of genetic testing for cancer?
(Image Credits – shutterstock.com)
- In general, there are no adverse events associate with most genetic testing if body fluids or inner cheek cells are use. However, an exception will be in pregnancy situations where amniotic fluid or tissue is obtain from around the fetus; this can cause miscarriage, but this is also very rare. However, if the genetic testing result is positive:
- It can cause emotional, social, or financial aftermath if an individual gets to know that they are at high risk of developing cancer. In fact, the susceptible individual may feel angry, disappointed, worried, fearful depressed, or guilty about the result.
- In some cases, it creates tension within the family because the result has revealed a secret about their health history.
- There is the possibility of genetic discrimination in the workplace because they will think you will not be able to carry out your duties effectively or you will have too much time off attending to your medical needs.
- You will have to adjust to a dramatic life changing habits in order to stay in reasonably good health for a long time. For example, you will be adjusting to new medications, regular exercise, change in diet and several follow-up with doctors and counsellor appointments.
- The information provide by genetic testing is limit, in the sense that it does not suggest that an individual with a positive result will certainly have the disease; it is only an indication that the person is at high risk, therefore necessary precautions need to be taken.
- If the individual who tested positive is already showing signs and symptoms, there is still no guarantee about the extent to which cancer will progress over a time. Other tests are therefore need to monitor the progression of the disease.
Other Useful Links:
- Berry DA, Iversen Jr ES, Gudbjartsson DF, et al. BRCAPRO Validation, Sensitivity of Genetic Testing of BRCA1/BRCA2, and Prevalence of Other Breast Cancer Susceptibility Genes. Journal of Clinical Oncology. 2002; 20: 2701-2712. doi: 10.1200/JCO.2002.05.12.
- Welcsh PL and King M-C. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum. Mol. Genet. 2001; 10:705-713. doi: 10.1093/hmg/10.7.705
- Kempers MJE, Kuiper RP, Ockeloen CW, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. The Lancet Oncology. 2011; 12:49–55.
- De Rosa M, Fasano C, Panariello L, et al. Evidence for a recessive inheritance of Turcot’s syndrome caused by compound heterozygous mutations within the PMS2 gene. Oncogene. 2000; 19:1719-1723.
- Béroud C and Soussi T. APC Gene: Database of germline and somatic mutations in human tumors and cell lines. Nucl. Acids Res. 1996; 24:121-124. doi: 10.1093/nar/24.1.121
- Kohno T, Nakaoku T, Tsuta K, et al. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res. 2015; 4:156–164. doi: 10.3978/j.issn.2218-6751.2014.11.11
- Kuroda M, Kiyono T, Oikawa K, et al. The human papillomavirus E6 and E7 inducible oncogene, hWAPL, exhibits potential as a therapeutic target. British Journal of Cancer. 2005; 92:290–293. doi:10.1038/sj.bjc.6602329 bjcancer.com
- Thompson HS, Valdimarsdottir HB, Jandorf L, et al. Perceived disadvantages and concerns about abuses of genetic testing for cancer risk: differences across African American, Latina and Caucasian women. Patient Education and Counseling. 2003; 51:217–227. DOI: https://dx.doi.org/10.1016/S0738-3991(02)00219-7