What is NEXTCancer

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.

What is DNA?

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.

What is cancer?

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.

How do genetic mutations occur?

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.

What is hereditary cancer?

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.

next-cancer-stats

Hereditary cancer syndromes

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:

HEREDITARY BREAST AND OVARIAN CANCER SYNDROME (HBOC)

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:

  • 1 or more women are diagnosed at 45 years or younger
  • 1 or more women are diagnosed with breast cancer before 50 years with an additional family history of cancer
  • There is breast and/or ovarian cancer in multiple generations on the same side of the family
  • A woman is diagnosed with a second breast cancer in the same or opposite breast
  • A woman has both breast and ovarian cancer
  • A male is diagnosed with breast cancer
  • There is a history of breast, ovarian and/or pancreatic cancer on the same side of the family
  • There is a history of breast and/or ovarian, pancreatic or male breast cancer in a family of Ashkenazi Jewish decent.

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?

  • Individuals with a family history suggesting an inherited pattern and early onset cancer, especially with regards to breast, ovarian, fallopian tube or peritoneal cancer
  • Individuals with an unknown family history and have been diagnosed with:
    – Breast cancer before the age of 50
    – Cancer in both breasts
    – Breast and ovarian cancer
  • Individuals with a family history of cancer
  • Individuals who have family member(s) with:
    – Breast Cancer before the age of 50
    – Cancer in both breasts (for the same individual)
    – Both breast and ovarian cancer in the same women or family
    – Ovarian cancer before the age of 30
    – Multiple breast cancers in the same family
    – Two or more primary types of BRCA1 or BRCA2 related cancers in a single family
    – Case of male breast cancer
    – Ashkenazi Jewish ethnicity

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:

  • Increase a woman’s chance of developing breast cancer to 50-85% and ovarian cancer to 15-54% by the age of 80
  • Increase a man’s chance of male breast, melanoma, pancreatic and prostate cancer

A BRCA2 mutation can:

  • Increase a woman’s chance of breast cancer up to 74% and ovarian cancer up to 12% by the age of 70
  • Increase a man’s chance of male breast, melanoma, pancreatic and prostate cancer

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.

nextcancer-ovarian

HEREDITARY COLORECTAL CANCER SYNDROMES

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.

HEREDITARY MELANOMA SYNDROME

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.

WHO SHOULD BE TESTED FOR HEREDITARY CANCERS?

  • Individuals with a personal or family history suggesting an inherited cancer risk
  • Features which may suggest hereditary cancer presence for testing include:
    – Cancer that was diagnosed at an unusually young age
    – Several different types of cancer that have occurred independently in the same person
    – Cancer that has developed in both organs in a set of paired organs, such as both kidneys or both breasts
    – Several close blood relatives that have the same type of cancer (i.e. a mother, daughter, and sisters with breast cancer)
    – Unusual cases of a specific cancer type (i.e. breast cancer in a man)
    – The presence of birth defects, such as certain noncancerous (benign) skin growths or skeletal abnormalities, that are known to be associated with inherited cancer syndromes
    – Being a member of a racial/ethnic group that is known to have an increased chance of having a certain hereditary cancer syndrome and having one or more of the above features as well

Test panels

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:

1. HEREDITARY CANCERS PANEL

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.

2. SPECIFIC HEREDITARY CANCER PANELS

All the below panels screen specific genes for an increased risk in that specific hereditary cancer:

  • BRCA Gene Panel: screens the BRCA1 and BRCA2 gene.
  • Breast Cancer Panel: screens up to 26 genes associated with an increased risk for hereditary breast cancer
  • Breast & Gynaecologic Cancers Panel: Screens up to 35 genes associated with hereditary breast, ovarian and uterine cancer.
  • Colorectal Cancer Panel: screens up to 28 genes
  • Gastric Cancer Panel: screens up to 19 genes
  • Hereditary Paraganglioma-Pheochromocytoma Panel: Screens up to 14 genes
  • Hyperparathyroidism Panel: screens up to 5 genes
  • Melanoma Panel: Screens up to 12 genes
  • Myelodysplastic Syndrome/Leukaemia Panel: Screens up to 45 genes
  • Nervous System/Brain Cancer Panel: Screens up to 40 genes
  • Pancreatic Cancer Panel: Screens up to 28 genes
  • Prostate Cancer Panel: Screens up to 15 genes
  • Renal/Urinary Tract Cancers Panel: Screens up to 30 genes
  • Sarcoma Panel: Screens up to 41 genes
  • Thyroid Cancer Panel: screens up to 11 genes

3. PAEDIATRIC ONCOLOGY PANELS

  • Paediatric Solid tumours panel – screens up to 48 genes which are associated with a hereditary predisposition to the development of paediatric solid tumours
  • Paediatric Hematologic Malignancies panel – screens up to 16 genes. Some of these genes are also associated with an increased risk for other cancers
  • Paediatric Nervous System/Brain tumours panel – screens up to 24 genes associated with an increased risk of developing cancers of the central and peripheral nervous systems in childhood and adolescence.

Genetic counselling for cancer screening

* 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.

What is the hereditary cancer screening process?

  1. We receive an email from the Patient requesting a Hereditary Cancer Test.
  2. If you are requesting this test without a Healthcare Professional (HCP), a Genetic Counselling Session must set up with one of the Genetic Counsellors (GC) in our preferred provider network. This session is either conducted face-to-face, via Skype or telephonically. Please note that this session is an hour in duration and the cost is not included in the test fee. The cost of this session is R950 and it must be paid directly to the Genetic Counsellor.
  3. If Hereditary Cancer Screening is recommended by your HCP or the GC, they must complete the Test Requisition Form and send it through to Next Biosciences.
  4. Next Biosciences will send you an instruction for payment to be made.
  5. Once payment is received, Next Biosciences will courier a Hereditary Cancer Screening kit to you for the sample to be collected (instructions provided on the kit).
  6. Once the kit is ready for collection by the courier, you contact Next Biosciences and we will arrange for the courier to collect the sample and ship it to the laboratory in the USA (turnaround time is 2-4 weeks).
  7. Once your results are ready, they will be sent to your HCP or the GC, who will explain your results to you and help you understand what they mean for you and your family.
  8. A post-test counselling session may be recommended with a Genetic Counsellor in cases of a positive result. This will be for your own account.