NEXTCancer is a test which analyses specific genes for harmful mutations which may increase your risk for developing cancer. This information will give you the power to help manage your risk by taking the necessary preventive steps, with the aid of your healthcare professional.
DNA carries the instructions our cells and tissues need to function, and it is found in almost every cell in our body. Each cell normally contains 2 identical sets of 23 different chromosomes, one set received from your father and the other from your mother. There are roughly 25 000 genes found within our chromosomes, and genes are the functional units of DNA. Genes provide the instructions to make proteins and other substances necessary for life.
Put simply, cancer is the uncontrolled growth of abnormal cells, anywhere in the body. It results from a mutation in an individual’s genes which results in a change in the way these genes control the growth and division of cells. A mutation occurs when a genes sequence of nucleotides / chemical bases is changed. This change is not always harmful. Some of these changes can be beneficial, some may have no affect and others may be pathogenic (disease causing). Pathogenic mutations are responsible for the development of cancer. Even though cancer is a genetic disease, it is also multifactorial; genetics, lifestyle, environment and hormones can all influence the development of cancer.
These genetic changes can occur randomly in one or a few cells in the body, through errors which occur when cells divide, through damage made to DNA through various environmental exposures or as a natural consequence of aging. These acquired changes are called somatic changes. Genetic changes can also be hereditary, carried by the mother and/or father and passed down to their children. These mutations are already present in the DNA of sperm and eggs cells which is why they can be passed down in families. Majority of cancers occur as a result of a somatic mutation, only 5 – 10% of cancer diagnoses are as a result of an inherited genetic mutation.
This is a cancer which develops as a result of an inherited genetic mutation. However, even if an individual has an inherited genetic mutation which is linked to a specific cancer, it doesn’t mean they will definitely develop cancer. Cancer is multifactorial, so a single mutation alone usually is not enough to cause cancer; severe genetic mutations, or a number of mutations are required before a cell will become cancerous. Therefore, if an individual carries an inherited genetic mutation, this is not a cancer diagnosis but an increased risk for developing cancer over their lifetime.
Hereditary cancer syndromes are characterised by cancers which have developed as a result of an inherited genetic mutation which predisposes an individual to a very high lifetime risk of developing cancer, the early onset of that cancer and the development of multiple independent primary cancers.
Common examples of Hereditary Cancer syndromes include:
There are genetic disorders characterized by inherited genetic mutations in one or more genes which predispose an individual to the development of cancers and their early onset. HBOC is associated with higher than usual levels of breast and ovarian cancer on the same side of a family.
There is a high change of a family having HBOC syndrome when:
The most common mutations causing HBOC in families are found in the BRCA genes. BRCA1 and BRCA2 inherited mutations account for 5% and 10-15% of all cases of breast and ovarian cancer respectively. With mutations in these genes, woman have an increased lifetime risk of developing breast and ovarian cancer, and men have an increased lifetime risk of breast and prostate cancer. There are also less common gene mutations associated with HBOC which include TP53, PTEN, CDH1, ATM, CHEK2, STK11 or PALB2.
Who should be tested for HBOC?
BRCA1 and 2 mutation testing is not recommended for people under the age of 18 as a child’s risk of developing a cancer associated with these mutations is extremely low, and there are no risk-reduction strategies specifically meant for children.
Why consider testing?
A BRCA1 mutation can:
A BRCA2 mutation can:
40% and 26% of women who are harmful BRCA1 and BRCA2 mutation carriers respectively, will develop collateral breast cancer, a new primary cancer in the opposite breast, before 20 years after their initial diagnosis.
This cancer syndrome is associated with higher than usual levels of colon and rectal cancer on the same side of a family. There are a few hereditary colorectal cancer syndromes which include Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch Syndrome, Familial Adenomatous Polyposis (FAP) and the hamartomatous polyposis syndrome.
Lynch Syndrome
This is an autosomal dominant cancer syndrome which increases the risk for developing colorectal cancer. Autosomal dominant means that only one mutation of a gene is required to be at risk for the development of this cancer syndrome. The mutated genes which are shown to be responsible for Lynch syndrome are MLH1, MSH2, MSH6 and PMS2. Lynch syndrome also increased the risk for the development of other cancers which include endometrial, stomach, ovarian, small bowel and pancreatic cancer.
FAP
This is an autosomal dominant cancer syndrome which greatly increases the risk for developing colorectal cancer. This disease is known to have a 100% penetrance, meaning any individual who has this disease will develop numerous adenomas throughout their colon, which will in most instances progress to cancer. The cause of this syndrome is a mutation in the APC gene.
This cancer syndrome is associated with higher than usual levels of malignant melanomas on the same side of a family. About 7 – 15% of cases of melanoma occur in families which have a family history of melanoma, however true hereditary melanoma cases are quite rare and familial melanomas are usually due to shared sun exposure experiences with family members with similar susceptible skin types. Around 45% of familial melanomas are associated with hereditary genetic mutations linked to two genes, CDKN2A and CDK4.
Li-Fraumeni syndrome
This in an autosomal dominant syndrome which is associated with an increased risk in a number of cancers, as well as the early onset of them. These cancers include soft tissue sarcomas, osteosarcoma, breast cancer, brain cancer, leukaemia and adrenocortical carcinoma. This syndrome is caused primarily by a mutation in the TP53 gene.
There are a number of test panels available to you and the choice of which test is most appropriate for you can be made with the help of your registered healthcare professional or a genetic counsellor*. All tests have a 2-4-week turnaround time and the require a saliva sample to be conducted.
The cancer screening panels include:
Screens up to 83 genes associated with an increased risk for all known hereditary cancers. The hereditary cancers include breast & gynaecologic system (breast, ovarian, uterine), gastrointestinal system (stomach, colon, rectum, small bowel and pancreas) endocrine system, genitourinary system (renal/urinary tract, prostate), skin system, brain/nervous system, sarcoma and hematologic system.
All the below panels screen specific genes for an increased risk in that specific hereditary cancer:
* Genetic Counsellors (GC) are healthcare professionals that specialise in medical genetics and counselling. They are registered with the HPCSA, and their professional healthcare services are accepted by medical aid funders.
Next Biosciences offers specialised genetic counselling to help determine the need for a hereditary cancer test by collecting a detailed personal and family medical history to determine the likelihood that a hereditary cancer exists in your family. Following this they will explain the test options available to you, including any associated benefits and limitations. Post testing, the GC will communicate your results and help you understand what they mean for you and your family; they will also provide you with support and help you make necessary health decisions which are right for you.
The cost of a Pre-Test Genetic Counselling Session is not included in the above test fees. It is a separate cost which must be paid directly to the Genetic Counsellor, and it can be reimbursed from your medical aid.
