Information for Women : Cancer and heredity

Contents

This brochure is published by the Information department of the Dutch Anti-Cancer Campaign/ KWF

January 1997

If this brochure is more than 3 years old, ask whether there is a newer version. The brochure is printed on environmentally friendly paper.

©KWF 1997

Who is this brochure for

Each year in the Netherlands, about 61,000 people discover they have cancer. Cancer is a disease which usually causes drastic changes in the life of the patient and his family. Often there is a point at which the patient asks himself precisely why he has got cancer. If cancer occurs from one generation to the next in one family, then the question arises of whether cancer is perhaps inherited.

This question cannot be answered with a simple yes or no. Cancer is a collective name for a larger number of diseases, for example lung cancer, bowel cancer and breast cancer. There are thus more than a hundred different sorts of cancer. Moreover several types of cancer can be distinguished in each sort.

There is no single cause responsible for the occurrence of all these sorts. There are a great number of causes, one of these can be heredity.

This brochure is primarily intended for those persons who have (had) various family members with cancer, and who are wondering exactly how heredity and cancer relate to each other.

In this brochure you can read what is known at present about the role of heredity in the formation of cancer. For a number of cancers we already know that they can be inherited. (see pages 11-14). In addition you can read about what you can do, if you suspect that an hereditary form of cancer occurs in your family.

If you still have questions after reading this brochure, then you can always ask your general practitioner or specialist. You can also contact one of the information centres listed on pages 24 and 25.

Different sorts of cancer

Cancer is a name that covers more than one hundred different diseases. A common feature of these diseases is a disturbance in the normal division of the body’s cells. This disturbance is always the result of damage to the genetic material in the cells. If cells keep on dividing needlessly then a malignant swelling (tumour) will occur. This tumour can occur in a particular organ, like the stomach, the prostate or the brain. A proliferation of cells can also occur in the blood, for example as with leukaemia, or in the lymph system, as with Hodgkin’s disease.

The different sorts of cancer each run their own course:

  • Different factors can play a role in their occurrence. Our life style, such as smoking, eating, drinking alcohol and sunbathing, plays an important role in this. Thus smoking increases the risk of lung cancer, and also, although to a lesser degree, the risk of bladder and cervical cancer. On the other hand, too much sun bathing produces a greater risk of skin cancer.
  • Patients often have completely different symptoms from their disease, depending on the sort of cancer they have been diagnosed as having.
  • The treatment not only differs according to the sort of cancer, but also even within one sort; one patient may be treated differently to another. This has to do with the stage of the disease and the cell type of a particular sort of cancer.
  • Another difference is the chance of a cure. One sort of cancer can be easy to cure, whilst with another sort the chances of a cure are very low.

Cancer in the family

Cancer is a disease which occurs frequently in our country. This is why, even by chance, cancer can occur more often in one family than in another. When cancer occurs in successive generations in one family, it is important to know whether it is the same sort of cancer or various sorts. If one sort of cancer or certain combinations of sorts of cancer occur in successive generations, then heredity is possibly the most important cause of its occurrence.

In practice it is really quite uncommon for various members of a family to have the same sort of cancer or the same combination of various cancers. Usually completely different sorts of cancer occur families in successive generations. These can be caused by very varied factors, such as smoking, excess use of alcohol, exposure to carcinogenic substances at work, such as benzene, or frequent sunbathing.

Causes

If the same type of cancer occurs in a family in successive generations, then that disease can occur as a result o various causes, such as:

  • An inherited sensitivity for a particular sort of cancer.
  • An inherited sensitivity for a disorder that can lead to a particular sort of cancer.
  • A genetically determined physical condition, through which one is more sensitive to certain carcinogenic influences from outside, like sun light.
  • The fact that various family members have a habit, like smoking, that increases the risk of having a particular sort of cancer.

When various family members have the same type of sort of cancer and it is not a hereditary tumour, what could be going on?

To get an idea of how everything fits together, let’s take skin cancer as an example.

Skin cancer is the most common sort of cancer in the Netherlands. Lots of sunbathing, often spending time on a sunbed or working in the sun a lot, all increase the chance of having this sort of cancer. That is true of everyone, but people with light blond or red hair, are more likely compared to others to develop skin cancer. They have a greater natural sensitivity to the dangerous consequences of ultraviolet radiation in sunlight or sunbed lighting. Just this genetically determined sensitivity alone means that skin cancer occurs more in red or light blond haired families.

There are, however, also families in which this sensitivity does not occur and where several people do have skin cancer. This can be because family members have the same type of job, for instance those who are engaged in agriculture, construction and road mending. They are, compared to others, more exposed to the carcinogenic action of ultraviolet radiation. The result of this can be seen in white families who have lived for a long time in the tropics.

Life style habits

Exposure to carcinogenic circumstances can be linked to an occupation but also to certain life style habits. Families can in fact, in successive generations, keep up certain habits which increase the risk of cancer. In a family with many smokers the risk of lung cancer is greater than in a family where there are few or no smokers.

Some families have certain eating or drinking habits such as the use of a lot of fat, a lot of salt or highly spiced food, or the drinking of much alcohol. Family members who maintain such habits, have more risk of acquiring certain sorts of cancer.

Summarising: A particular sort of cancer can occur more in one family than in another, because there:

  • is a genetically determined physical sensitivity, or,
  • has been greater exposure to carcinogenic circumstances.

Cancer and heredity

To gain more insight into the role of heredity in the occurrence of cancer, research has been carried out in families in which certain sorts of cancer occur frequently. From this it appears that in some sorts of common cancers, for instance lung cancer or stomach cancer, genetic predisposition does not play a significant role. In other common sorts, such as colon cancer or breast cancer, then heredity can be of crucial significance.

With heredity and cancer we also talk of a genetic predisposition or sensitivity for cancer. This sensitivity can be high or low. If sensitivity is low then other factors such as our life style play a greater role in the occurrence of cancer, than when sensitivity is high.

An example of a sort of cancer with a low genetic sensitivity is breast cancer .

An example of a sort of cancer with high sensitivity is retinoblastoma, an eye tumour which occurs in children.

Estimates show that about one half of one per cent of all people who acquire cancer each year have a sort with high sensitivity.

At present scientific investigations into the role of genetic predisposition in the occurrence of cancer have been greatly accelerated. With the aid of modern research techniques, like DNA testing, more and more is being revealed about which genes are damaged (gene: part of the body cell which contains genetic information).

It is not possible to indicate precisely for how many people with cancer, genetic predisposition is the most important cause.

How does genetic predisposition arise

Our body consists of small living organisms that we call cells. Each cell has a nucleus containing 23 pairs of chromosomes.Chromosomes consist to a large extent of DNA. This DNA contains all our genetic information. It has a structure which can be thought of as a long chain of building blocks. There are four different building blocks and the order of these blocks in the DNA determines the structure and characteristics of our body.

llustration of Chromosome pairs

XX – WOMAN

XY – MAN

Chromosome pairs

One chromosome pair contains a chromosome with genetic information from the mother and one with separate information from the father. Each separate chromosome of a pair, contains information for the same characteristics. The capacity for each characteristic thus doubly present.

Genes

Chromosomes are subdivided into genes, each with a fixed place. A gene is therefore a piece of chromosome that consists of DNA in which information for a genetic characteristic is stored. It is estimated that the human being has anything between 50,000 to 100,000 genes. Genes provide information to cells about what task that cell must perform. There are genes that are responsible for the blood group, for the colour of the eyes and for the development of a cell into, for instance, a muscle cell. There are also genes that ensure that a cell stops dividing, once this has been given a specific function.

Damage

We now know for a number of hereditary sorts of cancer exactly which damaged genes can be passed on from generation to generation. This is illustrated below using the retinoblastoma (eye tumour) to show how this occurs.

The healthy RB gene ensures that certain cells in the eye do not divide any more. But if the father or mother has had a retinoblastoma, then this gene can be passed on in a damaged form to a child. The cells of the eye mentioned above will also have this deviant gene. However these cells will not keep dividing. This is because there is still a healthy gene from the other parent. Someone with these genes still, of course, has a chance that in one of these cells a small change could occur in the healthy gene. Such a change is called a mutation. The consequence is that in children with a predisposition for retinoblastoma the brake on the division of such a cell fails and a tumour occurs.

Hereditary tumours

In this chapter the sorts of cancer described are those of which it is known that genetic predisposition plays a role in their occurrence. A number of very rare sorts such as the syndrome of Li-Fraumeni and neurofibromatosis are not included in this brochure.

In a number of sorts we already know exactly which genes are damaged, namely in retinoblastoma, dysplastic naevus syndrome, the MEN 2 syndrome, polyposis coli and to some extent also in inherited colon cancer and breast cancer.

How it passes from generation to generation, the inheritance pattern, can be read on page 15.

Retinoblastoma

This is a tumour of the retina of the eye. This sort of cancer occurs in young children. Retinoblastoma is a very rare sort of cancer. In the Netherlands about 15 children are diagnosed with this tumour each year. In 35 % of these patients heredity is involved. The majority of these tumours (65 %) arises without this tumour occurring previously in the family. Neverthless children who have acquired retinoblastoma without a clearly indicated predisposition in the family, can themselves be the progenitor of a family with hereditary retinoblastoma.

Dysplastic naevus syndrome

This is a genetic disorder of the skin in which a motley pattern of birthmarks (naevus = birthmark) arises. The number can vary from a few to hundreds. They are often irregular in shape and vary in size and colour. They frequently occur in unusual places on the body, such as on the scalp or in skin folds. Such birthmarks can degenerate into a particular form of skin cancer: a melanoma. About 10 % of all melanomas occur among people with dsyplastic naevus syndrome.

Polyposis coli

This is a disorder of the colon whereby hundreds of, originally benign, polyps occur. If these polyps are not removed they can degenerate into colon cancer. Of all the patients with colon cancer about 1 % are the result of polyposis coli.

Tumours of the endocrine glands

Endocrine glands are small internal organs that make and secrete hormones into the blood. These hormones are necessary for the functioning of our body.

In endocrine glands an hereditary form of cancer can arise, the so-called MEN syndrome. MEN is an abbreviation of Multiple Endocrine Neoplasia. This means literally ‘multiple neoplasm of the hormone producing glands’. What is unusual is that cancer does not appear in just one place, but frequently in several glands of this type. This can occur simultaneously or over a period of time. A distinction is made between the MEN 1 and the MEN 2 syndromes.

In MEN 1 syndrome certain tumours can occur, either simultaneously or not, in the pituitary gland, the parathryoid glands and the pancreas, the so-called Islets of Langerhans tumours.

The MEN 2 syndrome consists of tumours of the adrenal medulla, the parathryoid glands and a rare form of thryoid cancer, the ‘medullar thyroid carcinoma’. These tumours too can occur simultaneously.

Hereditary colon cancer, breast cancer and ovarian cancer.

It is estimated that about 5 % of all patients with colon, breast or ovarian cancers have acquired the disease because of a genetic predisposition. There is some knowledge about where the genetic damage is sited for inherited colon cancer and breast cancer.

A number of points distinguish these hereditary sorts of cancer from ‘ordinary’ colon cancer, breast cancer and ovarian cancer.

The hereditary sorts are generally diagnosed at a younger age, namely between 30 and 50 years of age. The ordinary sorts occur mostly between 50 and 70 years of age.

In addition, persons with one of these hereditary sorts have a greater risk of another sort of cancer. Women with colon cancer have a greater risk of cervical cancer. It is suspected that people with this sort of cancer also possibly have a higher risk of cancer of the stomach, ovaries and kidneys.

Women with hereditary breast cancer more often have the disease in both breasts in comparison to women who have had the ordinary sort of breast cancer. In some families, in addition to breast cancer, there are also a greater number of women with ovarian cancer than would normally be expected.

For women with hereditary ovarian cancer, the risk of breast cancer is also increased.

More information

The Foundation for the Tracing of Hereditary Tumours has published separate folders about the following hereditary tumours:

  • dysplastic naevus syndrome
  • polyposis coli
  • hereditary colon cancer
  • hereditary breast cancer

The address of this Foundation can be found on page 23.

A separate folder about MEN 1 and MEN 1 syndromes can be obtained from the Dutch Anti-Cancer Campaign.

There are a number of patients’ associations that specifically aim at making contacts between fellow sufferers and families where a hereditary sort of cancer occurs. On page 20-22 you can read more about these organisations.

Inheritance pattern

If in a family one person has a hereditary sort of cancer, then it does not necessary follow that all family members will acquire this disease.

Inheritance of such a disease occurs according to a certain pattern. Often this is the autosomal dominant pattern. Autosomal means that the inheritability is not tied to gender. Boys and girls have equal chances of inheriting the predisposition. Dominant means that if one of the parents has a predisposition for a hereditary sort of cancer, each child has a 50 % chance of having this predisposition. In most children who have inherited the predisposition, such a cancer will finally arise.

The hereditary tumours which were described on the previous pages, all have this autosomal dominant pattern of inheritance.

Determining the risk

In order to know what risk the members of a family run, then sufficient details of certainly two, and preferably three generations must be available. For some sorts of hereditary sorts of cancer the symptoms of the disease occur quite early on. Family members in whom no abnormalities are found during check-ups, have, after reaching a certain age, no increased risk for that particular sort of cancer. This is true, for instance, of polyposis coli. If a patient’s brother or sister are still free of large numbers of polyps in the colon by the age of 45, then the chance is very small that they will thereafter develop polyposis coli.

For those sorts of hereditary cancer whereby the genetic damage is known, there is now a DNA test which in a number of cases permits a more careful assessment of which family members are at risk and which are not. You can read more about the DNA test on pages 18 and 19.

Family testing

If cancer occurs frequently in your family and you are wondering whether inheritance is in any way responsible, it is good to check whether it is one or several sorts of cancer. If there has been one sort of cancer in various members of the family, or a combination of sorts such as were mentioned on page 13, then you should discuss with your general practitioner whether investigating the role of inheritance would be worthwhile. You can also phone one of the organisations that does heredity research for information (see pages 22 and 23).

If one member of the family has one of the hereditary sorts of cancer mentioned above, then the question arise of who else in the family should possibly be given an extra check-up. This could be brothers and/or sisters as well as the children of the patient. First of all, we have to find out which members of the family run the risk of developing such a tumour. This type of investigation is carried out, amongst other places, within the Hereditary Tumours Out-patient Clinics of the University Hospitals and of the specialised cancer hospitals in Amsterdam and Rotterdam, at the Foundation for the Tracing of Hereditary Tumours, or at one of the organisations for genetic research, the Clinical Genetics Centres. At the last-named centres, patients and risk-bearing family members can also be given advice if they want to know whether it is responsible to have children. More information about these organisations can be found on pages 22 and 23.

During family testing the first step is to see exactly how the inheritance pattern runs. With the aid of information about family members who have (had) cancer and information about the cause of death of all deceased family members a ‘medical family tree’ can be drawn. The creation of a medical family tree is not simple and sometimes impossible as a result of lack of information.

Monitoring

On the basis of the family tree investigation the only conclusion that can be drawn is who in the family possibly has a 50 % chance of being at risk. Then the question arises of whether it is worthwhile regularly monitoring a person at risk for (a pre-stage of) a specific tumour. In practice this is often a difficult issue because at present there is (still) no reliable test available for some tumours.

For members of families in which polyposis coli, hereditary colon cancer, breast cancer or ovarian cancer, dysplastic naevus syndrome or MEN 2 syndrome occurs, there is such a preventative test. Preventative testing is intended to discover the disorder in as early a stage as possible, so that effective treatment can be performed. This treatment is then given before a tumour has developed or while it is still very small.

Thanks to the developments in genetic research, nowadays the risk can be better assessed with a DNA test in a number of cases than with family tree research (see next page).

Foundation for the Tracing of Hereditary Tumours

This Foundation has as its objective the encouragement and co-ordination of family testing. The Foundation collects data from families with hereditary cancer and notes whether risk-carrying family members are treated or are monitored. The Foundation also maintains contacts with the patients’ associations.

DNA testing

For a DNA test a small amount of blood is needed from the person making the request. In the laboratory DNA is isolated from the white blood cells. If it is not yet known which mutation occurs in the family, then first of all, a DNA test has to be carried out on a family member with a particular sort of hereditary cancer. The order of all the building blocks, which form the DNA code of the altered gene is therefore determined for that person. By comparing this to the normal order the mutation can be traced. This test can take some time to perform.

Once the mutation in the family is known, then it is possible to carry out a mutation analysis among family members. The DNA is cut into pieces using chemical scissors at fixed places. Using a specific scissors for each mutation,this thus produces strands of differing lengths, which are then sorted according to length. This produces a fixed pattern, unless the mutation is present. In that case cutting points either appear or disappear, resulting in longer or shorter DNA strands. The DNA of a person is thus tested to see whether it shows the normal pattern of strands, or whether the pattern is that seen in the mutation in the family. A mutation analysis generally takes several months.

Predisposition – yes or no.

Unfortunately DNA tests still are unable in a considerable number of cases to provide definite proof or whether someone has a predisposition or not. Then monitoring remains necessary. If the DNA test provides sufficient information, then for each family member there are two possible outcomes: he or she has inherited either the healthy or the disease-bearing chromosome (= predisposition). If a family member seems to have no predisposition, then regular monitoring is not needed. Also any children of this person will not get the disease. If however a predisposition for a certain sort of hereditary cancer is shown to be present, then monitoring or treatment is needed. The age at which this occurs depends on the sort of hereditary cancer.

Knowing whether or not there is a predisposition, can have consequences for choices concerned with education and profession, and also in planning a family. Family members who wish to have DNA tests performed must also be extensively informed about the consequences of the tests.

Contact with fellow sufferers

A number of special patients’ associations have been set up for people with hereditary sorts of cancer. Women with hereditary breast or hereditary ovarian cancer can get help from these patients’ associations:

  • National Contact Body for the Counselling of Breast Cancer Patients (LCBB)Post-box. 289,
    3000 AG Rotterdam
    Telephone 010 – 436 53 28
  • National Contact Point for Young WomenTelephone 071 – 541 88 68
  • The Olijf Foundation, Network for women with gynaecological cancerPost-box 1478
    1000 BL Amsterdam
    Telephone 020 – 570 05 45

The M.E.N. Pressure Group

The M.E.N. Pressure Group is intended for everyone who is involved in one way or the other with the MEN 1 or MEN 2 syndromes. This can be as patient or as the partner, but also as the child of a patient, another family member or simply as a sympathiser. The Pressure Group expects to make a contribution to the prevention of MEN 1 and MEN 2 syndromes. Their attempts to achieve this goal include: the collection and provision of information, the maintenance of telephonic contact with members requiring support, the organisation of regional and national meetings, the stimulation of discussion groups, participation in (medical) work groups, and the publication of the magazine M.E.N. Kontact. More information from:

  • M.E.N. Pressure GroupVredehofje 8
    6467 ER Kerkrade
    Telephone 045 – 541 75 34

Polyposis Contact Group

This Contact Group is intended for patients, partners, children and family members who are confronted with the hereditary disorder polyposis coli. The Contact Group was started in 1988. One of its most important activities is mutual contact with the aim of learning from each other’s experiences. In each region the group has regional contact persons who are dedicated to this cause.

With the aid of experts in the medical, ethical and psychological field the aim is to foster the provision of information to the families involved.

You can get in touch with this group by writing or phoning :

  • The National Secretariat of the Polyposis Contact GroupLooierij 31
    1825 JN Alkmaar
    Telephone 072 -561 06 22

Working Group for Children with Retinoblastoma

Within the “Parents, Children and Cancer” Association, a special Working Group is active consisting of parents of children with (or have had) a retinoblastoma. The Working Group was set up to provide parents who meet the special problems of a hereditary sort of cancer, with the opportunity of exchanging experiences.

For more information you can contact:

  • The “Parents, Children and Cancer” AssociationAchterdijk 85
    3985 LA Werkhoven
    Telephone 0343 – 55 19 69 (secretariat)
    Telephone 0545 – 27 40 21 (Chairman of the Working Group)

Research Centres

The organisations listed below are where you can obtain answers to questions about heredity such as whether a certain sort or combination of sorts of cancer occurs in various persons within one family. For a consultation with an expert of one of these organisations a referral card from your general practitioner or specialist is required.

Do you have any questions?

If you have any questions after reading this brochure, don’t just keep them to yourself. Personal questions are best discussed with your general practitioner. If you have questions about cancer that are more general, or you want to talk to someone else about your questions before you visit your doctor, then you can also ask for help at the Information Centre of the Dutch Anti-Cancer Campaign and at the Integrated Cancer Centres.

Information Centre

Dutch Anti-Cancer Campaign

The Information Centre of the Dutch Anti-Cancer Campaign is situated at:

Sophialaan 8, 1075 BR Amsterdam.

In the Information Centre someone is available to discuss your questions. The centre is open from Monday to Friday between 9.00 and 17.00 hrs. For information in brief you can just walk in. If however you wish to discuss matters personally at length, then it’s better to make an appointment. You can also write or phone. There is a free Help and Information line 0800 – 022 66 22 (on working days between 10.00 – 12.30 hrs and 13.30 – 16.00 hrs. Your call will be received on a telephone answering system. By pressing or dialling numbers on your phone you can choose to talk to someone or order a folder. Orders from organisations and institutions can only be handled in writing!

Suggestions about the contents of this brochure can be made in writing to the Information Centre of the Dutch Anti-Cancer Campaign.

Integrated Cancer Centres

Information about cancer is also given by the Integrated Cancer Centres. Besides information for social workers, these centres also supply information to patients and the public.

Information Dutch Anti-Cancer Campaign

Information about cancer and anti-cancer by means of:

folders brochures documentation video programmes training
free help and information line for personal help and information
0800 022 66 22
The Information centre of the Dutch Anti-Cancer Campaign is open from 9am to 5pm
Sophialaan 8, 1075 BR Amsterdam
Extended visits, preferably by appointment