The question familial cancer “detectives” try to answer: “What shall I do if I have inherited a mutation that increases the risk of cancer?”

• Between 10% and 15% of cancer cases have a hereditary component; the rest are due to environmental factors.
• Specialists in family cancer search family trees for relatives who may have inherited mutations that increase the risk of cancer. The aim is to improve prevention
• The Familial Cancer Unit at the Spanish National Cancer Research Centre (CNIO) studies more than 600 cases a year. 30% are healthy people with a family member with cancer in which a hereditary mutation has been identified.
• “A person carrying a mutation that increases the risk of cancer can make decisions that help to prevent it”, according to the CNIO researcher, María Currás.

There are genetic alterations – mutations – that increase the risk of cancer and that are transmitted from parents to children. If those who have inherited them knew that they were carrying them, they could adopt prevention measures for their individual risk. Depending on each case, they could be monitored to detect the cancer as soon as possible, or even remove a healthy organ for preventative reasons.  Of course, it all depends on carriers knowing that they are.

The public health system has specialists who, like detectives, search family trees for people at risk of hereditary cancer, to help them prevent it.

María Currás, Head of the Familial Cancer Unit at the Spanish National Cancer Research Centre (CNIO), analyses more than 600 cases a year at her practice at the University Hospital of Fuenlabrada, which is associated with CNIO. More than a quarter of her cases are healthy people, but they have a relative –mother, brother, sister, aunt, cousin…– with cancer, in whom a genetic alteration that increases the risk of cancer has been identified.

Healthy relatives come to the familial cancer consultation wondering whether they have inherited this mutation. Knowing they have could save their lives.

“If a person knows that he/she is carrying a mutation that increases the risk of cancer, he/she can make decisions that will help prevent it”, according to Currás. “In some types of cancer, one such decision could be the preventive removal of an organ that is still healthy; another, more common decision is to enter a monitoring programme to detect the cancer as soon as possible”.

Thousands of cancer cases in which prevention could be more effective

Cancer can be suspected of having a hereditary component when it appears at an early age – for example colon cancer under the age of under 50 or 55, or breast cancer under the age of 40 -, when the person develops multiple tumours, or when several family members have the same or related cancers. These tumours represent between 10% and 15% of all cancer cases (the rest are due to environmental factors and lifestyle, such as the consumption of tobacco, alcohol, unhealthy diet and exposure to radiation).

In many of them (between 5% and 10% of all cancer cases) the causative mutation is known and can be detected with a blood test. Considering that in Spain alone, there are almost 300,000 new cancer diagnoses each year, several thousand people in Spain could take preventive measures appropriate to their higher level of risk if they knew they carried hereditary cancer mutations.

This is the reason behind the 180 family cancer clinics at Spanish hospitals (data from the Spanish Society of Medical Oncology). Some of these hereditary cancer specialists explained how they try to keep ahead of the disease during a course held recently at the CNIO. Their workload has not ceased to grow in recent years.

“Knowing that you are a carrier can save your life”

The most common sequence of their work is as follows. Oncology and other specialities ask the family cancer clinic to assess the patient and their family history of cancer; if a hereditary cancer mutation is found after a genetic study, the patient’s family tree will indicate “which relatives to study, and in what order”, says Currás.

Parents, descendants and siblings at risk of having inherited the mutation, who have been warned by the patient, can go to the clinic and also undergo a study that will determine whether they are carriers, after receiving the proper genetic counselling.

In 2024 at the Fuenlabrada clinic “29 gene mutations were detected that would imply a possible preventive surgery when affecting women”, according to Currás. Identifying these carriers has a cascade effect, because their relatives could also benefit.

Pioneering Angelina Jolie

Rafael Morales, Head of the Medical Oncology section at the University Hospital La Mancha Centro, in Alcázar de San Juan (Ciudad Real), mentions the case of the actress Angelina Jolie, who decided to have her ovaries and breasts removed as a preventive measure on learning that she carried a mutation in the BRCA1 gene, which increases the risk of breast and ovarian cancer, despite not having developed the disease. She sought to prevent the cancer that led to the death of her mother, grandmother and aunt.

Since the Jolie case more than a decade ago, work in family cancer clinics has increased substantially. “Knowledge of the genes involved in cancer is increasing rapidly”’ says Currás.

More than 100 genes involved in hereditary cancer

Around 105 genes related to hereditary cancer are already known. In each one, there may be hundreds of different mutations.

According to Morales, “it is important to point out that being a carrier of a mutation does not mean that you will get cancer, but rather that the probability of developing one or several types of certain cancers is higher than in the general population”. In hereditary cancer, the influence of familial mutations is added to that of environmental factors and lifestyle. 

Hereditary breast and colon cancer

To what extent do mutations associated with hereditary cancer increase the risk of developing cancer? It all depends on the altered gene. It is estimated that up to 60% of women with a BRCA1 mutation will develop breast cancer in their lifetime. In Lynch syndrome, up to 80% of people may develop colon cancer in their lifetime and up to 60% of people may develop endometrial cancer in their lifetime.

“Hereditary predisposition to breast and ovarian cancer syndrome and hereditary predisposition to hereditary non-polyposis colon cancer syndrome, or Lynch syndrome, are the most prevalent in our hereditary and familial cancer practice”, says Morales. Other syndromes that are on the rise in recent years are hereditary prostate cancer and hereditary melanoma.

“Greater awareness among the population”

People who believe they are at risk, because they consider that there are many cases of cancer in their family also go to familial cancer consultations.

For Morales, this should be more common: “Anyone who knows of several cases of cancer in their family should go to their primary care doctor for an initial assessment. Should it be suspected that the patient could be a person or family with a high risk of hereditary predisposition to cancer, he/she will be referred to a genetic counselling unit for further study”.

When a case arrives in which a causative mutation has not been previously identified, the specialists start their detective work: “It is very common for information to be confusing and incomplete: it is known that one or another relative died of cancer, but neither the type, nor the age are known… we cannot always help,” says Juana María Cano, oncologist at the University General Hospital in Ciudad Real. 

The genetic study is often not indicated; it is known beforehand that its result would not provide relevant information, and may even generate a false sense of security: “There are cases in which it is suspected that there could be a genetic cause, but we are unable to identify it”, says Cano. “There is no known mutation, which does not mean it does not exist”.

Such families could still join monitoring programmes which would help to detect a potential cancer as soon as possible.  Morales says, for this reason “it is important to raise awareness among the population”. 

The Familial Cancer Clinical Unit at the CNIO combines patient care with research. In 2022, the identification of a new candidate gene for breast cancer predisposition was confirmed, which increases the risk of breast cancer by 2.5 times compared to the general population.  

Clinical care that helps research

The Familial Cancer Clinical Unit at the CNIO receives particularly complex cases from all over Spain.  This service is essential for the research it carries out, which is focused on identifying new genetic factors involved in cancer and collaborating in the interpretation of genetic variants of unknown significance.

More specifically, it participates in the IMPaCT-GENóMICA and IMPACT-VUSCan projects, the biggest Spanish project to identify genes that increase the risk of cancer.  It also contributes to the Spanish Variant Database for Hereditary Cancer (SpadaHC), a collaboration between CIBERONC (CIBER of Cancer), IDIBELL and ICO, which stores more than one million variants from around 4,300 patients and to which around twenty laboratories contribute.  

Further information:

The biggest ever Spanish project to identify genes that increase the risk of cancer kicks off  – CNIO

A study by the CNIO Familial Cancer Unit helps identify a new candidate gene for breast cancer predisposition – CNIO