- Hereditary mutations: Inherited genetic mutations passed from parent to child, from generation to generation. - Spontaneous mutations: Mutations arise from a variety of sources, including mistakes or abnormalities in DNA replication or transcription, spontaneous lesions and transposable genetic elements. - Induced mutations: Mutations caused by environmental factors, e.g. chemical agents, air pollution, radiation and heat.
The mutations, regardless of types, can lead to abnormal protein synthesis and protein malfunction. This causes miscommunication among cells, resulting in rapid and uncontrollable cell growth which can potentially turn to cancerous cells. However, it often takes more than just a single mutation to cause a particular type of cancer. Therefore, not all people who inherit a mutation in cancer related genes, e.g. tumor suppressor gene, proto-oncogene, or DNA repair gene will develop cancer within their lifetime.
A genetic disease is defined as a disease that is caused by a change or mutation in an individual's DNA sequence, affecting protein formation. A genetic disease can be caused by a mutation in a single gene (monogenic traits) or multiple genes (complex traits). Mutations affect different organs in the body, causing a wide range of genetic disorders, for instance: - Cystic fibrosis : Cystic fibrosis is an inherited disease characterized by the buildup of thick, sticky mucus that can damage several organs. Cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein is responsible for regulating the flow of salt (chloride cells) and fluids in and out of the cells in different parts of the body. The mutation leads to uncontrolled chloride cell transportation, causing sputum production in the lungs, mucus in the pancreas and other organs in the body. This sticky mucous can potentially lead to infections in the lungs, respiratory tract and digestive system. - Cancers : Certain types of cancer are inherited, such as breast cancer. BRCA1 (BReast CAncer gene and BRCA2 BReast CAncer gene 2) are genes that produce proteins that help repair damaged DNA. Functioning as tumor suppressor genes, both genes control cell growth and cell death. Mutations of BRCA1 and/or BRCA2 can lead to hereditary breast cancer and ovarian cancer. Women with mutated BRCA1 have an increased risk to develop breast cancer by 60-80% and ovarian cancer by 30-45%. Women with mutated BRCA2 have an increased risk to develop breast cancer by 50-70% and ovarian cancer by 10-20%. Men with mutated BRCA1 and BRCA2 show an increased risk of breast cancer by 1-10% and pancreatic cancer by 2-5%.
Genetic mutations or pathogenic variants can be divided into two broad categories based on the tissue from which they originate; germline mutation and somatic mutation. Germline mutation occurs in a sperm cell or an egg cell. It is then passed directly from a parent to a child at the time of conception. As the embryo grows, the genetic mutation from the initial sperm or egg cell is copied into every cell in the body of the baby. As the pathogenic variant affects reproductive cells, it can pass from generation to generation. Cancers caused by germline mutations are called inherited or hereditary cancers. Germline mutations account for approximately 5%–10% of all cancers.
Genetic mutations usually involve changes in the order of the base pairs of genetic material, including substitutions, deletions, additions or shifts. Mutations cause protein malformation and protein malfunction which can potentially lead to certain diseases. When genetic mutations develop in the genome, these mutations can be further analyzed by the experts in bioinformatics. Once obtained, the results will be mutually collected as international or national database, allowing the correlation between genetic mutations and inherited diseases to be disclosed. Nevertheless, it is important to know that not all mutations can cause diseases.
Genetic test kit is a testing apparatus used to collect samples, such as saliva and blood for genetic analysis to determine genetic mutations and their potential effects on health and well-being. Using the apparatus in the kit, the sample is collected and preserved for DNA extraction. Subsequently, nucleotides will be sequenced and genetic mutations will be identified, if any. Obtained results of individuals from sequencing analysis will be then compared with national database where abnormal genes are detected. With medical advances in genetics, several sequencing methods are available with different advantages and limitations. However, the most popular technique is Next-Generation Sequencing or NGS technique.
What can you know from genetic test?
- General health status, e.g. nutrient sensitivity, such as carbohydrate and lipid. - Risk of developing certain diseases - Drug response and drug allergy - Hereditary diseases that guide for family planning
Several sample types can be used for genetic testing, e.g. tissue, blood, saliva and buccal cell. However, to select the sample type, it depends on genetic testing technique or method.
- Knowing and understand your risks to develop certain diseases. - Planning your proactive healthcare action to minimize the risk of developing certain diseases. - Managing family planning in accordance with testing results. Particularly for cancers, genetic testing combined with early detection can help to detect the abnormality before the condition progresses, allowing for effective treatments conducted in a timely manner. Cancer screening and early detection increase the chances of detecting certain cancers earlier, when they are most likely to be curable with greater survival rates. If cancer is detected at its earliest stage, the chance of being cured drastically increases while improving patient’s quality of life.
- Anyone who is at risk of hereditary diseases. - Anyone who may be at risk of sporadic cancer defined as cancer that occurs in people who do not have a family history of that cancer or an inherited change in their DNA that would increase their risk for that cancer. - Anyone who wants have proactive healthcare plan and preventive strategies. - Patients who need genetic testing for aiding diagnosis, determining disease prognosis and treatment guideline. - Patients presenting with symptoms associated with genetic conditions.
1. Pre-counseling : Prior to the test, you should consult with a doctor or a genetic specialist to understand genetic testing, including its purpose, result interpretation and limitations. To fulfill your medical purposes, appropriate genetic test kits need to be advised. 2. Sample collection : Make an appointment in order to collect samples. 3. Laboratory process : Once the samples are collected, they will be preserved as specified and delivered to a laboratory unit for further analysis. 4. Obtaining the results : Depending on analysis techniques, it normally takes 4-6 weeks until the results can be obtained. 5. Post-counseling : Once the result is revealed, a doctor or a genetic specialist will thoroughly explain your results based on findings. Proactive healthcare planning and additional investigation can be made accordingly.
1. Negative results mean no genetic mutation is detected at the particular time that the test was conducted. However, negative results do not guarantee that mutations will not develop in the future. If your result is negative and you do not have family history of cancer, you still have the same cancer risk as the general population. 2. In some circumstances, you may have mutations in other locations or other genes that have not been tested in this genetic testing, although your results show negative. Please be aware that mutations in other locations or other genes can increase risk of cancer. 3. If mutations are not firmly associated with cancers, the results normally report as “variant of unknown significance or VUS”. This result may be interpreted as “uncertain” and may not be sufficient to assist current health care decisions. 4. The results might show genetic changes that are common in the general population without cancers. These mutations are called "genetic diversity" and they are not associated with any risk of developing cancer. 5. This test is only applied to hereditary cancers. Besides genetic alterations, several factors play an important role in developing cancers, e.g. diet, infection, radiation, chemicals, behavior and environment. 6. The genetic testing only shows current mutations on the tested genes. The results do not guarantee that mutations will not occur the future. You should consult with a healthcare professional if you have any concerns regarding the test.
Positive result means significant gene mutation is detected. If positive result is shown, it means you may have an increased risk of getting disease, compared to the general population. However, an increased risk does not affirm that you will definitely get disease, instead it only suggests that you are at greater risk of developing disease. - If the test result is positive, it is highly recommended to have regular health check-up in combination with other relevant investigations or laboratory tests, e.g. blood tests and imaging tests in accordance with findings obtained from the genetic testing. - Lifestyle modifications to minimize the chance of getting disease include smoke cessation, regular exercise, consuming healthy diets and refraining from carcinogens.