This is how genetic studies work

Hospital de LlobregatAlarms are raised for the women of the Maas family with Carmi's breast cancer diagnosis. She was the second in the family to suffer from it before she was forty years old. One of her nine sisters was diagnosed with the disease in her 30s. In addition, the mother contracted cancer. The question posed by Maas was reasonable: Did the statistics affect them, because their number was large? Were they unlucky? Or was there a genetic reason?

A year later, a third sister was diagnosed and nerves flared. Although they had to wait before getting the answer they were looking for, they eventually learned that the cause was genetic: half of them had variants typical of hereditary breast cancer, BCRA1 and BCRA2. Although this does not mean that they all have cancer, they are more likely to develop cancer than the rest of the population.

The case of this family helps reveal the work and importance of genetic studies, which are DNA analyzes that make it possible to identify mutations associated with certain types of cancer. On the one hand, it helps in knowing whether the patient's disease is due to genetic inheritance. On the other hand, if confirmed, they would prefer early detection of immediate relatives who may be at higher risk of contracting the disease.

“From the beginning we saw that in this family there were several diagnoses, in different generations, of the same cancer that could have a genetic origin. “We had to try to find an explanation,” recalls Monica Salinas, genetic counselor at the Catalan Institute of Oncology (ICO). ) at Hospitalet de Llobregat. Based on Carmi's diagnosis, the Center's Genetics Board activated the protocol to conduct a study of her genetic material – based on a blood sample – and search for DNA changes. This resource is activated when there is more than one case of the same cancer in a family in Unusually young age – for example, the average age for breast tumors to develop is around 50 years.

Tests found that Carmi was positive for one of the typical hereditary breast cancer mutations, which increases her chances of developing breast cancer, but also ovarian cancer. In fact, it is estimated that 50 to 60% of women with BCRA may develop the tumor before the age of 70. This prompted them to warn their sisters to conduct a genetic study. “Years ago, when they did the study on me, it took about a year to get the results. While we were waiting, the third case in the family appeared,” Carmi explains. “That made us all study,” says Encarna, one of the sisters.

Decision making

Genetic studies begin with an interview with the diagnosed patient who carries the mutation to create a family tree. This first step tends to take longer, because patients are hesitant. This is not surprising at all: knowing whether parents, siblings, or even grandparents have suffered from cancer is relatively simple. But as the generation advances, things get more complicated. It could be that the family is very large – as is the case with diamonds – or the relationship is not good, or they live far away or they don't know each other. Did the maternal grandmother or paternal grandfather's sister suffer from cancer? There are those who cannot answer the question and the box remains empty.

The family tree should be able to trace up to three generations, but the personal and family history of any patient is confidential and cannot be taken directly from clinical records. Thus, Salinas should start by checking whether any of his first- and second-degree relatives — parents, siblings, grandparents — have a history of cancer. “How many siblings do you have? Are you from the same parents? Did your eldest suffer from cancer? What kind at what age?” he asks. This is for each member. Many patients arrive at the consultation fully informed with very detailed information. Others have few answers. But the important thing is to answer only the obvious.

The nurse then collects the same information from aunts, grandparents, and cousins. The goal is to determine whether there is a genetic predisposition in one branch of the family – the father or the mother – which means that the patient, but also his or her children, grandchildren, and even great-grandchildren, may be at greater risk of developing cancer. For example, Encarna tested positive for the mutation and her main concern was whether her daughter Paula, who was a young girl at the time, also inherited it. “The information dropped like a bomb, but I was more worried about it than I was,” he admits.

Paula lived in anxiety for the following years, until she reached adulthood and was legally able to undergo genetic study. Not for the result, but for the inability to take the test. “My mother didn't want me to have her when she was so young because she was afraid I would live in fear. But I knew it was possible to have the mutation and I thought knowing that would help me make decisions.” In fact, he only lasted another year: at the age of 19, he took the test, and the result was positive. “I'm a carrier of this mutation and I'm proud to have been able to find out. I've already started processing my request for a prophylactic mastectomy. I can go to the operating room now or wait and I'll probably end up doing it anyway and with greater risk.”

Candidates

Patients are referred to the ICO Hereditary Cancer Genetic Counseling Program in five cases: When the same type of cancer – or related tumors, such as breast, ovarian or pancreatic cancer and melanoma – has been repeatedly diagnosed in different organs of the same type. Family branch and different generations; If the cancer appears when they are young; If this is not the first diagnosis. If the cancer is generally uncommon in both sexes, such as breast cancer in men, or rare, such as thyroid cancer, or if a mutation in the family that causes the cancer has already been identified.

According to Salinas, genetic studies will likely not reveal any changes. People who do not carry the disease will have the same chance of developing cancer as anyone else. However, if a mutation is confirmed, as occurs in half of the women in the MAS family, the genetic study will be expanded to include other family members, healthy or with cancer. This study is always voluntary – no one can be forced to undergo it – and the results allow personalized recommendations, which can be curative (when there is already a diagnosis) or preventive (before there is a diagnosis).

When there is a change inherited from generation to generation, it does not mean that all family members must have the gene or develop the tumor. The fact that there are several cases of cancer in the same family does not mean that there must always be a hereditary genetic component behind it. It is estimated that only 5 to 10 percent of tumors are the result of germline genetic changes—found in all of the body's cells—and that the remainder are influenced far more by lifestyle habits than errors in our DNA.

Additionally, Salinas explains that there are a few types of cancer for which genetic study is recommended, and he explains that not all of them are done for the same reason. Breast cancer, metastatic stomach tumors and colon tumors are performed when they are suspected of genetic origin. On the other hand, ovarian testing, although it can also be inherited, is performed regardless of personal history (age) and family history (if there are more cases in the family) because it allows to determine the best treatment for each condition.