Introduction to breast cancer genetics and family history Including: What is familial breast cancer? • What are genes? • Breast cancer genes • How common is familial breast cancer?
ABOUT THIS BOOKLET This content is from a larger guide called “The best treatment: Your guide to UK services for people with a family history of breast cancer”, Edition 1, Breakthrough Breast Cancer. Other booklets in this series: • Finding out about your family history of breast cancer • Genetics testing – a guide for people with a family history of breast cancer • Early detection and risk factors – a guide for women with a family history of breast cancer • Risk-reducing surgery – a guide for women at high risk of developing breast cancer • More support and information – a guide for women with a family history of breast cancer BREAKTHROUGH’S HEALTH INFORMATION Breakthrough Breast Cancer is dedicated to improving and saving lives through breast cancer prevention, early diagnosis, more targeted treatments and better services for everyone affected by breast cancer. Our health information is based on the latest research and reviewed by clinicians, scientists and people affected by breast cancer. Breakthrough Breast Cancer’s other health information materials include: • ‘Touch. Look. Check.’ Our breast awareness leaflets and posters • Breast Cancer Risk Factors: The Facts booklet • A4 fact sheets summarising the research for specific breast cancer risk factors: Alcohol, Breastfeeding, Deodorants and antiperspirants, Hormone replacement therapy (HRT), Obesity, Puberty and menopause, The pill, Pregnancy, and Soya and phyto-oestrogens. • The best treatment: Your guide to breast cancer treatment in England and Wales All of our publications are available free of charge within the UK. Please order online at breakthrough.org.uk or call our freephone Information Line on 08080 100 200. Breakthrough Breast Cancer is a charity registered in England & Wales (No.1062636) and Scotland (No.SC039058)
What are genes and how are they linked to breast cancer?
O I T C S U IC D T O E R N T E IN G O T
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What is familial breast cancer?
WHAT IS FAMILIAL BREAST CANCER?
See page 13 for more information about a family history of breast cancer.
Familial breast cancer is cancer that occurs more frequently within a family than would be expected in the general population.
See page 54 for more information about breast cancer risk factors.
Most cases of breast cancer are not familial and occur when there is either no family history or only one case in older relatives, which would be expected to occur by chance. This is referred to as sporadic breast cancer. Familial breast cancer is different from sporadic breast cancer because: • Your family history means that the likelihood of you developing breast cancer can be estimated. • You, or members of your family, may be at an increased risk of developing breast cancer, and at an earlier age, compared with the general population. This means that you may be anxious about breast cancer even while not affected by the disease. Worries can be for yourself or for other members of your family, and this can affect many aspects of your life. We can’t always say what causes breast cancer, but the increased risk of breast cancer for those with a family history of the disease might be caused by inherited factors (genes) or a combination of inherited, lifestyle and environmental factors.
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INTRODUCTION TO GENETICS
WHAT ARE GENES? Cells in the human body contain chromosomes, which are made up of strands of DNA. Specific sequences of DNA in particular sections of the chromosomes are called genes. Human cells contain about 20–25,000 genes and each gene provides instructions to tell the cell how to function. The instructions that a cell requires depends on what type of cell it is. You can imagine that a muscle cell will need different instructions to a brain cell, and likewise a brain cell to a breast cell. Genes are responsible for how your body develops, looks and works. Your genes are unique to you – nobody else has the same set of genes, unless you have an identical twin. Humans have 22 pairs of chromosomes plus the sex chromosomes (XX and XY), so have two copies of each gene, one on each chromosome. HOW ARE GENES INHERITED? Genes run in families and are passed on to you from your parents. Everyone has two copies of every gene. You will have inherited one copy of each of your genes from your mother and one copy from your father. This is how characteristics, including family resemblance and an increased risk of a disease, are passed down from one generation to the next. Depending on the combination of genes you inherit you will end up with some traits that resemble your mother and others that resemble your father. DNA is made up of small building blocks, which are arranged in a particular order. Since all genes are made up of DNA it is a change in the sequence of this DNA that leads to a fault in the gene. We all carry a number of faults in our genes, but only some of these will alter the way the gene functions.
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THE BEST TREATMENT Your guide to UK services for people with a family history of breast cancer
Breast cancer genes
BREAST CANCER GENES
For more information about TP53 see page 29.
When people talk about familial breast cancer they often talk about inheriting faults in one of the breast cancer genes: BRCA1, BRCA2 and TP53. There are also other genes that can affect a person’s risk of developing breast cancer; however, little is known about them and we can’t test for them at present. Research is continuing into what role these other genes might play. Everyone has two copies of each gene and faults in the breast cancer genes BRCA1, BRCA2 and TP53 are associated with a high risk of developing breast cancer. Faults in the genes are rare and so many people with a family history of breast cancer won’t have a fault in one of these genes. When a person is found to carry a fault – or mutation – in a BRCA gene, this means they have one faulty copy and one normal copy of the gene. Regardless of whether or not they have had, or develop, cancer there is a chance that this person may pass the faulty copy on to their children. WHAT IS THE CHANCE OF INHERITING A FAULT IN A BRCA GENE? The children of a person carrying a fault in the BRCA1 or BRCA2 gene have a one in two (or 50%) chance of inheriting that fault. This is because they inherit one gene copy from each parent, and they are as likely to inherit the normal copy as they are to inherit the faulty copy. This one in two chance is for each child, male or female. If you are a carrier of a gene fault and have two children, that doesn’t mean that one will inherit a faulty BRCA gene and one won’t – each has a one in two chance of inheriting the faulty gene. Inheritance of BRCA gene Parents Bb
Bb = one copy of faulty BRCA gene (increased risk)
bb
bb = both copies normal BRCA gene (population risk)
Children Bb
Bb
bb
bb
Possibilities of inheritance THE BEST TREATMENT YOUR GUIDE TO UK SERVICES FOR PEOPLE WITH A FAMILY HISTORY OF BREAST CANCER
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INTRODUCTION TO GENETICS
What women say We were surprised that the gene was inherited through my grandfather’s line – we didn’t realise this could affect the men in the family as well. Breakthrough Campaigns & Advocacy Network member
It is important to remember that if you have inherited a faulty BRCA gene it does not mean that you have inherited breast cancer. You have inherited a high risk of developing breast cancer, which means you are more likely to develop the disease than people who do not have a BRCA fault. Since BRCA genes are inherited from both parents, faults in these genes can pass down the male or the female line of the family. This means that, for example, a daughter can inherit a faulty BRCA gene from her father, even if her father has not had breast cancer. In addition, a faulty gene cannot ‘skip’ a generation, although some relatives who carry the faulty gene may not develop cancer. The table below shows on average how likely someone is to inherit a faulty BRCA gene depending on which of their relatives is found to be carrying a BRCA gene with a fault. These figures are only estimates, however, and the likelihood may vary depending on a person’s particular family history of breast cancer.
See page 25 for more information on the risk of developing breast cancer.
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RELATIVE WHO HAS A FAULTY BRCA GENE
CHANCE THAT YOU ALSO CARRY THE FAULTY GENE
CHANCE THAT YOU DO NOT CARRY THE FAULTY GENE
Mother or father
1 in 2 or 50%
1 in 2 or 50%
Sister or brother
1 in 2 or 50%
1 in 2 or 50%
Identical twin
1 in 1 or 100% (definitely do)
0 in 1 or 0%
Aunt, uncle, grandparent
1 in 4 or 25%
3 in 4 or 75%
Great aunt or cousin
1 in 8 or 12.5%
7 in 8 or 87.5%
If someone does not inherit the faulty gene found to be running in the family, then they have two normal copies of the BRCA1 or BRCA2 gene, and they cannot pass on the fault to their children. However, they and their children could still get sporadic breast cancer – most cases of breast cancer are not related to an inherited fault in these breast cancer genes.
THE BEST TREATMENT Your guide to UK services for people with a family history of breast cancer
How common is familial breast cancer?
HOW COMMON IS FAMILIAL BREAST CANCER?
What the guidelines say: Genes involved in breast cancer
The majority of those who develop breast cancer do not have a significant family history of the disease. For most women, getting older is the biggest risk factor for developing breast cancer. It is important to remember that:
It is important to recognise however, that most family histories of breast cancer are not due to a mutation in BRCA1, BRCA2 or TP53 genes. Familial breast cancer: The classification and care of women at risk of familial breast cancer in primary, secondary and tertiary care, National Institute for Health and Clinical Excellence, 2004.
• four out of five breast cancers occur in women aged over 50. • breast cancer is rare in women under 40 years old. About one in 20 breast cancers are due to inherited faults in breast cancer genes such as BRCA1 or BRCA2. This accounts for about 2,400 cases each year in the UK. Around a further one in eight breast cancer cases are thought to be due to other genetic factors, where most of the specific genes involved are not yet known but are likely to be ‘variants’ – altered versions of normal genes – which may contribute to the development of breast cancer. This accounts for approximately another 4,800 to 7,200 diagnoses each year in the UK. Having a family history of breast cancer means that you may be more likely to develop breast cancer, and at a younger age, but it does not mean that you will definitely get the disease.
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