A bank of biological samples from thousands of Brazilians could help the Unified Health System (SUS), which is public and free, identify people at higher risk of developing certain types of cancer. In the future, the SUS could offer these individuals more personalized prevention and screening strategies. Developed at Hospital de Amor in Barretos, a city in the Southeast region of Brazil, the initiative collects genetic, epidemiological, and lifestyle data from people with and without cancer to evaluate and develop risk prediction tools better suited to the population.
The project already has 4,062 participants and nearly 40,000 blood samples. The goal is to enroll at least 8,000 people (half with cancer and half without) over the next two years. The first types of cancer being studied are breast, colorectal, and cervical cancer. A paper describing the creation and characteristics of this biobank was published in the journal iScience and received funding from FAPESP .
Although the project involves the creation of a new biobank focused specifically on genomic studies and precision medicine, it was not built from scratch. The initiative leveraged the robust infrastructure of the institutional biobank at Hospital de Amor, established in 2006, to structure its new database. This biobank already holds more than 420,000 biological samples from over 55,000 donors.
Rui Manuel Reis , the scientific director of the Hospital de Amor Institute for Teaching and Research and coordinator of the study, says the initiative aims to fill an important gap in precision medicine. More than 90% of people included in large-scale genomic studies investigating cancer risk are of European ancestry. In other words, much of the available knowledge about the relationship between genetics and cancer risk has been derived from populations that are genetically very different from the Brazilian population. "We can't develop precision medicine using a template designed for a European population, with European genetics and a European lifestyle," the researcher states.
Polygenic risk score
One of the tools that the researchers intend to develop is the polygenic risk score. This score differs from genetic tests that identify well-known hereditary mutations, such as alterations in the BRCA1 and BRCA2 genes. These mutations significantly increase the risk of breast and ovarian cancer.
Reis explains that, in most cases of cancer, there is no single genetic alteration that can explain the increased risk of developing the disease. Instead, there are hundreds or thousands of small variations scattered throughout the DNA that, individually, have a very small effect. Some may slightly increase the risk, while others may decrease it. The polygenic score aggregates this information and calculates the combined effect of these variants to estimate a person's genetic predisposition to a particular tumor.
Each variant represents a small portion of the risk, and the score adds up these portions. While the result does not predict whether a person will develop cancer, it allows for the identification of individuals with a lower or higher genetic predisposition. "For each individual, we assess the presence of thousands of genetic variations that, when added together, may indicate a higher or lower risk. This is what we call a polygenic risk score," he explains.
The researcher points out that polygenic scores are nothing new. They have already been developed based on large international genomic studies and are beginning to be used to estimate the risk of certain diseases, including cancer. However, the vast majority of these scores were constructed and tested primarily in people of European ancestry.
Therefore, before applying these same tools in Brazil, it is crucial to determine if they can adequately estimate risk in a population as ethnically diverse as the Brazilian one. "Before applying this standard [the score determined for European populations], we need to know if it actually applies to the Brazilian population," Reis argues.
Other factors
An important point is that a high risk score does not necessarily mean that a person will develop cancer. The disease results from a combination of genetic predisposition and other factors, such as diet, obesity, physical inactivity, smoking, and various environmental exposures. One of the distinguishing features of the Brazilian study is precisely this: in addition to collecting blood samples, the Hospital de Amor project gathers information from participants through a comprehensive questionnaire about their lifestyle, diet, occupation, and other potential risk factors. The researchers aim to identify which genetic variations are associated with cancer in this population and how these variations relate to the ancestry and living conditions of Brazilians.
According to Reis, the data obtained thus far confirm the high degree of racial mixing in the country's population, with contributions from European, African, Indigenous, and Asian ancestries. Genetic composition also varies among individuals and across different regions of Brazil. The plan is now to investigate how ancestry is associated with the risk of developing certain tumors and how it influences the performance of polygenic scores. "We have a very rich biobank of genetic material combined with a very comprehensive epidemiological questionnaire. We'll be able to study how genetic predisposition interacts with environmental and lifestyle factors and, in the future, develop risk models that are better suited to Brazilian reality," says the researcher.
Three preventable cancers
The decision to start the project with breast, colorectal, and cervical cancers was not random. According to Reis, they were chosen because they are important in the country and there are established measures for their prevention, screening, and early detection. Mammograms, cervical screenings, and tests to detect colorectal abnormalities (such as fecal occult blood tests and colonoscopies) can help prevent or diagnose these cancers at earlier stages, improving treatment options and prognosis.
This is where polygenic scores may find an application within the SUS in the future. "If it's possible to identify who has a higher predisposition to a particular cancer, that information could be combined with other risk factors to guide prevention and screening strategies," says the researcher.
For example, a person classified as high-risk for colorectal cancer could receive more attention regarding modifiable risk factors. If future studies demonstrate a benefit, this person could follow a different screening strategy than someone at low risk, such as being referred for a colonoscopy at an earlier stage. The same reasoning could be applied to other cancers.
Impact on the SUS
Today, researchers are analyzing millions of genetic variations in each participant to determine which variants truly matter. Once the most relevant ones are identified, it is expected that a future test will only require a blood sample to identify dozens or hundreds of them. "We're building scientific evidence on which scores will be useful for the Brazilian population. If those markers are validated in the future, the idea is to identify people at higher risk and develop more personalized prevention and screening strategies," says Reis.
For now, this tool is not ready for implementation in the public health system. The scores must first be defined and tested on a larger number of people before being validated at other centers. "The goal of this work is to support a tool that can be rolled out across the entire SUS, but before that, it must be validated," Reis notes.
According to Reis, several tests are already on the Brazilian market that promise to estimate different risks based on genetics. However, many of these tests are based on research conducted abroad and have not been validated in the Brazilian population. "When it comes to a disease like cancer, we need to generate our own evidence before bringing these tools into clinical practice."
The study published by the group does not present a ready-to-use Brazilian risk score yet. For now, it describes the infrastructure created to obtain these results. The most advanced findings thus far relate to colorectal cancer and are expected to be presented in another paper to be published shortly. The group also plans to expand the biobank to study other types of tumors, such as lung, pancreatic, and melanoma, and to include patients from remote regions that are underrepresented in genomic studies. They will do so through the Hospital de Amor network, which operates in those regions.
Reis believes that creating a dedicated database is the best way to ensure Brazil's participation in advances in precision medicine. "By consolidating this database, we ensure that the Brazilian population isn't excluded from precision medicine. The goal is to understand the interaction between genetics, lifestyle, and environmental factors, as well as to develop prevention strategies that are more tailored to our country's reality," he concludes.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
