What are genes?
We inherit traits from our parents via our genes which are the basic building blocks of inheritance. They contain DNA which carries “instructions” which control the way our cells grow, age and behave. Everyone has two copies of each gene; one inherited from each parent.
We each have about 25,000 genes. Normally they ensure that our cells grow, reproduce and die in a controlled way in order to keep our bodies healthy, but they can sometimes become damaged or lost, or make additional copies.
How are genes damaged?
Cancer can be caused by gene alterations you were born with, or by genes that are damaged as a consequence of other factors.
All cancers develop because of gene changes. Usually, these changes are due to chance or to factors such as ageing, exposure to carcinogenic substances or to damaging environmental effects like sunshine, radiation exposure, pesticides, cigarette smoke or alcohol. Exposure to these carcinogens can sometimes cause changes to genes that control how our cells grow, allowing a tumour to develop.
These damaged genes are not inherited from your parents, and you can’t pass them on to your children.
What is a tumour?
Tumours are lumps or growths of abnormal tissue. The cells which make up our bodies don’t last forever, so for our tissue to survive, old cells must die by a process known as apoptosis or programmed cell death. New cells must be created by mitosis or cell division, and this regular turnover of cells keeps our bodies functioning well.
During this process, genes can become damaged or altered. This can mean that the cell receives the wrong instructions, and it can grow out of control, accumulating into a tumour. It’s thought that a cell requires several mutations before it becomes cancerous.
How common is hereditary breast cancer?
Only 5-10% of all breast cancers can be attributed to inheriting a faulty gene.
If an individual carries a cancer-causing fault in a gene, there is a 50% chance that they will pass that damaged gene on to their children. It’s important to note that not everyone with these gene mutations will go on to develop cancer as the mutations also rely on other factors such as environment and lifestyle.
For example, the risk of getting breast cancer is now thought to be approximately 57% for BRCA1 mutations, and 49% for BRCA2. 40% of women with a BRCA1 mutation develop ovarian cancer by age 70 and 18% with BRCA2.
This compares with a lifetime risk of approximately 12% for non-inherited breast cancer and 1.3% for ovarian cancer in the general population. These risk estimates may be revised in the future as new research results become available.
What are the BRCA1 and BRCA2 mutations?
The most researched and well-known genetic mutations associated with breast cancer are in the BRCA1 and BRCA2 genes.
These genes normally produce tumour suppressor proteins that protect against cancer development, but when they become altered or mutated they’re no longer able to repair DNA damage. As a result, cells then accumulate more genetic damage, which can lead to cancer.
Inherited breast cancers account for 5-10% of all breast cancers and of these, BRCA mutations carry the highest risk. They also account for about 15% of all ovarian cancers. These cancers tend to occur more often in younger women and men, compared to breast cancers which are not hereditary.
Jewish people who can trace their ancestry back to Central or Eastern Europe (Ashkenazi Jews) have a higher prevalence of BRCA1 and BRCA2 mutations than people in the general population.
BRCA1 mutation predisposes women to breast and/or ovarian cancer. Breast cancer in BRCA1 mutation carriers is often Grade 3, triple negative, and occurs at a younger age than non-hereditary breast cancer.
Male BRCA1 carriers are unlikely to develop breast cancer, but they have a heightened risk of developing prostate cancer.
BRCA2 mutation predisposes women to breast and ovarian cancers although the risk is lower than with BRCA1. It is frequently associated with male breast cancer.
BRCA2 mutations are also linked to a variety of other cancers including pancreatic, melanoma, and stomach cancer, and to prostate cancer in men.
Other breast cancer susceptibility genes:
Scientists are now able to detect a number of gene mutations which contribute to a higher than normal risk of breast cancer, and the list is continually growing. BRCA1 and BRCA2 still confer the highest risk of breast and ovarian cancer.
- TP53: This is a tumour suppressor gene which normally helps to control cell division and growth. Mutations in this gene can cause Li-Fraumeni syndrome which confers an increased risk of breast cancer as well as other cancers such as leukaemia, sarcomas, brain and adrenal tumours.
- PTEN: This gene normally regulates cell growth. Inherited mutations in this gene can lead to Cowden Syndrome. This can cause both benign and cancerous tumours in the breast and growths in the thyroid and digestive tract.
- CDH1: This is a tumour suppressor gene which is associated with hereditary diffuse gastric cancer. Women with this gene mutation also have a higher risk of developing lobular breast cancer.
STK11: This is a tumour suppressor gene. Mutations in STK11 can lead to Peutz-Jegher’s Syndrome, which causes pigmented spots on the lips and in the mouth and polyps in the gastrointestinal tract. It also increases the risk of several cancers including breast and ovarian.
- PALB2: This gene partners with BRCA2 to repair DNA and suppress tumours. Mutations lead to a higher risk of breast cancer.
- ATM: This gene is normally involved in DNA repair. People with one abnormal copy have an increased risk of breast cancer.
- CHEK2: This is another tumour suppressor gene, and mutations can also increase breast cancer risk.