What is Cancer?

What is the relationship between genes and cancer?

What is the genetic study?

• If you notice a bump, long-lasting pain, an injury or ulcer which will not heal, a spot or freckle which alters its shape, size and/or colour, a skin lesion which has appeared recently but continues growing, as well as bleeding or irregular haemorrhages.
• If you cough a lot or suffer from persistent hoarseness, if your urinating or intestinal habits change frequently or have lost weight for no apparent reason.

Cancer is a group of illnesses by which the organism produces too many malign cells (known as cancerous or cancerigenic), with some typical features of behaviour and uncontrolled growth (growth and division beyond normal limits), invading the surrounding tissue.
Cancer is more and more frequent in our society.
The incidence of cancer in Spain increases every year. It is the second cause of deaths in our country right after cardiovascular problems.
It is estimated that one in every three men and one in every five women will develop a tumour in their lives.
All types of cancer are caused by alterations in the genetic material of the cells which can be due to dangerous external agents (cancerigenic), such as radiation, contact with some chemicals, infectious agents or errors that can occur during the normal replication of the DNA and which are not corrected.
Tumours originated by these causes are called sporadic or non-hereditary.
Another cause of cancer is being born with an error in our genetic material (DNA).
When this is the main cause for the occurrence of the illness we speak about hereditary tendency to cancer or hereditary cancer.

People are formed by millions of cells, each one of them containing all the information necessary for life. We will call the smallest unit of information GENE (nowadays, we know more than 30,000 genes) and each of them is responsible for a specific body function. Genes gather, thus making chromosomes. All this information is what we call genetic material or DNA. People have 46 chromosomes grouped in pairs, that is to say, 23 pairs of chromosomes. At the moment of conception, when the ovule and the spermatozoid join to create the embryo, this INHERITS one chromosome of each of the 23 pairs from the father and one of each of the 23 pairs from the mother to create its own 23 pairs of chromosomes.
This genetic information is the one that will give us all different characteristics, like the eye or skin colour, height, etc. And, of course, they are also in charge of controlling all the cells in our body.

Mutation is an alteration in the genetic information (DNA) of a live being, thus producing a change of characteristics or function.
The genetic unit that can mutate is the gene.

What is the relationship between genes and cancer?

Nowadays, some GENES which participate in the process of occurrence of the illness have been identified.
In 90 or 95% of the cases of cancer, we are born with our genes working correctly until, due to external reasons, because of errors which may happen during the normal replication of the DNA or because of time, our genetic material, which used to work well, starts misfunctioning. When genes adopt alterations or mutations, these prevent them from performing their task properly.
Initially, the fact that a copy of the gene does not work well will not imply a problem, but if for the same aforementioned reasons, the other copy also goes wrong, the function of this gene will stop being carried out, and in this situation is when a cell may change from normal to cancerigenic.
That is to say, for a normal cell to become cancerigenic both copies of the gene which controls its function have to go wrong. This is the normal and most habitual step to start cancer. We call this sporadic cancer.
In the remaining 5 or 10% of cases, we may be born with one of the two genes of the pair altered or mutated (patogenic mutation), that is to say, we have a misfunction present in all the cells of our body. This mutation has been inherited from our father or our mother, although it may occur at the moment of fecundation. In this case we speak about hereditary cancer.

This does NOT mean that we have inherited cancer, but that we have a greater risk or tendence to suffer from the illness than the rest of the population. The tumour will only appear when the second copy of the healthy gene alters due to external factors (mentioned above)
In order to be able to say that a person or a family have a higher risk of suffering from a certain tumour than any other individual of the population in general, we have to evaluate the family history first.
In this type of families, several tumours of the same type are observed, or different tumours which are related, and there are several generations implied (grandfather, father, son); they are also diagnosed at a younger age than habitually.

When we have a history such as this, we can suspect that we are before a family with hereditary tendence.
Having a genetic characteristic of this type does not mean that your children certainly have it too. Depending on each gene’s heredity pattern type, the probability to share this characteristic with one’s children varies.

Dominant autosomic heredity pattern: in case it is this type of heredity, the probability that the offspring share the mutation is 50%.
This means that each time a child is begotten he/she will have 50% of hereditary probability, at random, and it is the same for both sexes.

Recessive hereditary pattern: in this type of heredity, in order for the children to share the mutation both parents must be bearers of a mutation. That is to say, they have to inherit an altered gene from each parent, and, the same as in the dominant autosomic heredity pattern, it is the same for both sexes.

If the person does not bear the genetic mutation present in the family, he/she will not be able to transmit it, and their children will have the same probability to suffer from cancer as any other person of the population in general.

The genetic counselling in hereditary predisposition to cancer is the process of information and communication to people and families, about how high their risk of developing tumours in their lives is, depending on their personal and family health history.

At the genetic counselling units we speak about:

• Identification of the relatives who are at risk.
• The available measures for prevention and early diagnostic adapted to their risk.
• The implications of this genetic susceptibility.
• The possibility to carry out a genetic study by means of molecular diagnostic.
• The probability to have or transmit certain genetic susceptibility to develop tumours.
• Evaluation of the personal and family needs according to their level of risk.
• Planning the health measures adapted to their level of risk.

In order to have a correct evaluation of the risk it is fundamental to have a complete family medical record which includes:

• Information of at least three generations of the family (both mother and father sides), including diagnostics of cancer.
  
• Documentation which allows the confirmation of the diagnostics of any tumour or associated illnesses, as well as the age at the diagnostic, death and type of afectation.

Those families in which certain types of tumours appear repetitively in different generations.
Those people who have had a tumour diagnosed at a young age.
When different types of tumours appear in a family, if they are known to be related with the syndrom of hereditary predisposition to cancer.

The genetic study consists of a blood test out of which the DNA is obtained, with the objective of determining if you are bearer of a genetic alteration in any of the genes implied in the hereditary susceptibility to cancer.
The technique used for the genetic test is complex and it will often take long to obtain the result.

This test is carried out by taking blood to a member of a family afected by cancer, choosing the most suitable candidate according to the personal and family medical record.

As any other procedure, the genetic study has its benefits, limitations and risks which the individuals and the families will have to consider depending on their personal circumstances.

The most relevant benefits are related with:

• Improving the use of the risk of cancer.
  
• Avoiding the doubt and the anxiety caused by the risk of having cancer.
• Helping making decisions of behaviour and lifestyle.
• Informing and advising the rest of relatives.

The main limitations are::

• Not all the mutations which imply a greater risk can be detected.
  
• Some results are difficult to interpret.
• The results indicate probability, not certainty of developing cancer.

Among the most relevant characteristics we would like to point out:

• Possible psychologic disturbance such as anxiety, depression, sense of guilt.
  
• False sensation of confidence.

Positive Result: It is the case when a mutation is detected causing an alteration in the gene’s performance and, therefore, main cause for having the illness.
A positive result will allow us to do the study to other members of the family, healthy or afected by cancer, to adequate the measures of prevention and/or early diagnostic of the illness.
The person to whom the mutation is detected will be known as bearer and has a high risk of developing cancer than the general population.
Those people in the family who do NOT have the mutation are called NON-bearers and their risk of developing cancer is the same as that of the general population.
There may be a case when we do not find a mutation; we call this Non-informative result. This result does not allow us to study the rest of relatives, but we do offer them all prevention and/or early diagnostic measures of the illness depending on the risk that has been stablished according to the family record.
The last possible result is that a mutation is detected of which we do not know if it is related with the appearance of the illness in the family. This is what we call Uncertain Clinical Significance. With this result we can not study the rest of the relatives either: we will consider and use it as Non-informative.

Once you have the result, it is very important to tell the relatives the possibility of visiting the genetic counselling Unit to have the test done or to learn about the prevention and/or early diagnostic measures suitable for each one of them.

The colon, the caecum and the rectum are part of the digestive system, specifically, of the large intestine. The colon is an approximately one and a half metres long muscular tube. The colon’s main function is to continue absorbing water from food as well as storing faeces.

The colorectal cancer consists of the uncontrolled growth of abnormal cells at this point of the intestine.
Colon cancer is one of the most frequent tumours around us, being the second most frequent cancer among both men and women.

There are several risk factors related to colon cancer: age is an important risk factor, it is more frequent among people older than 50, increasing progressively from this age. Most cases are diagnosed between 65 and 75 years old, although some cases may occur between 35 and 40 years old.
Other risk factors are the consumption of fat and red meat, obesity, tobacco and a high consumption of alcohol. People who suffer from the Crohn illness, ulcerous colitis and those who have personal or family antecedents of colon cancer have a higher risk than the general population.
Colo-rectal cancer develops little by little, most times as a consequence of minor lesions called polyps which appear on the walls of the intestine. Most polyps are benign, but certain types of polyps may evolve into cancer as time passes by.
If polyps are removed early enough, the risk of cancer can be prevented.

Most colon and rectum cancers are "sporadic" that is to say, they are not hereditary but due to alterations in the genes produced all along a person’s life as a consequence, among other causes, of environmental factors, age, hazard, etc.

Only 5% of all cases of colon cancer occur in families with a medical record of colon cancer. In these cases it is necessary to consult your doctor to see if there is a need to carry out a family study which discards the hereditary predisposition syndrome.

We suspect that there is hereditary predisposition when:

1. Colo-rectal cancer is diagnosed at a young age, before 50.
2. There are three or more close relatives (parents, siblings or children) affected by colo-rectal cancer or related tumours (womb, ovary, brain tumours...)
3. A Familial Adenomatous Polyposis is diagnosed (>20 or more than 100 polyps)

• Familial Colon Polyposis is an unfrequent illness, only 1% of all colo-rectal cancers, and it characterises by the appearance of hundreds of adenomatous polyps in the colon and rectum. Besides, polyps may also appear in the stomach and the small intestine. It is caused by a genetic alteration in the APC gene.

There is also a minor type of polyposis in which people also develop polyps in all the gastrointestinal system, but less of them, generally less than 100. It is caused by alteracions in the APC or the MYH genes.

• Non-Polyposic Hereditary Colo-rectal Cancer (NPHCC) or Lynch Syndrome is the most common type of hereditary colo-rectal cancer. It is between 2% and 5% of all cases of colon and rectum cancer. It characterises by the early development of colo-rectal cancer and it tends to imply several lesions at once or a second cancer, after some time, in the colon or rectum as well as tumours in other organs (endometrium, stomach, pancreas, urinary system, ovary, biliary system and small intestine). The genes MLH1, MSH2 and MSH6 are related with this syndrome; changes or alterations in these genes are responsible for most NPHCC.
• People with NPHCC have a higher risk of suffering from colo-rectal cancer or womb or uterus cancer.

Colon cancer (RCC) is a tumour which we can forestall. We count on highly effective strategies to reduce both incidence (number of cases) and casualties. With this target, the screening programmes try to identify the RCC at early stages. Nowadays there are tests which allow us to detect and diagnose colon cancer early, such as examining blood in faeces and colonoscopy.
Those patients with a higher risk of hereditary colo-rectal cancer will have screening tests and their frequency stablished by their responsible doctor or specialist depending on their family and personal medical record.

Breast tumour is the most frequent among women, and the third among general population. The age when it most often appears is the group older than 65.
There are different risk factors related to breast cancer, some of which are related to our lifestyle, such as tobacco or alcohol consumption, overweight or using contraceptives for a long time. Other factors are related to personal factors, such as age, increasing from 50 years old onwards.
The presence of a family record of breast cancer is an important risk factor, but we must consider that it may be due to factors shared among the members of only one family.
Several genetic alterations which predispose to breast and/or ovary cancer have been discovered. The genes implied in hereditary breast and ovary cancer are geen BRCA 1 and BRCA 2. When these genes function correctly, they protect us from the uncontrolled appearence of tumours; but when they are altered they increase 50-60% the risk of developing cancer before 70 years old.

A family record with several cases of breast cancer does not imply necessarily the presence of hereditary genetic alteration. Only between 5-10% of all cases of breast cancer diagnosed will be hereditary.

We suspect of a high risk of Hereditary Breast and Ovary Cancer when in a single family the following family antecedents appear:

• Two or more close relatives affected by breast/ ovary cancer at young ages (<50 years)
• Breast cancer diagnosed before 30 years of age
• Breast and ovary cancer in the same patient
• Bilateral breast cancer diagnosed before 40 years

The early diagnostic of breast tumours allows the reduction of the impact on your health and quality of life,  favouring a quick recuperation. For this reason, from the genetic counselling Unit we will put at your and your relatives’ disposal all those mesures of control and prevention adequate to your level of risk of suffering from tumours due to High Hereditary Predisposition to Cancer, in a personalised way and depending on the latest technologies available.