How many people have cancer risks without knowing it

One in 20 people in the general population have genetic variants that can increase the risk of developing cancer

A study of more than 400,000 participants estimates that one in 20 people carry genetic variants that increase the risk of cancer.

Current findings may challenge clinical practice that may personalize genetic screening for people with a family or history of cancer.

Genetic tests to study DNA to assess cancer prognosis are mainly performed in people with high risk factors or a family or personal history of the disease.

These tests are required when there is definite clinical suspicion as part of the diagnostic process or to identify family members at risk.In this context, clinical guidelines, such as the National Comprehensive Cancer Network (NCCN), set a risk threshold (usually greater than 5%) to recommend its operation, trying to balance clinical effectiveness and healthcare costs.

The study, released by researchers at the Cleveland Clinic, found that the general population, regardless of family or family history, developed cancer.This result, published in the journal, suggests that it does not detect risk according to current clinical guidelines.

"Joshua's findings are consistent with cancer," said Jos Arbesman, a researcher at the Cleveland Clinic and one of the study's directors."Our result shows how strong the differences in the risk of cancer are. useful."

How many people have cancer scars without knowing it?

The true prevalence of Gercher genetic variants associated with cancer susceptibility in the general population is, until now, unknown because most previous studies were based on cancer or a relevant family history.

With the goal of knowing how many people carry genetic variants with a risk of cancer, the researchers analyzed genomic data from one of the largest available databases: the All of Us cohort of the National Institutes of Health of the United States. With the results, they hoped to determine whether it would be necessary to reconsider the current recommendations on the use of genetic tests.

The study included 414,830 participants with whole-genome sequencing data.The authors selected 84 cancer susceptibility genes in a multigene panel and applied strict criteria to identify gene variants classified as pathogenic or potentially pathogenic through the ClinVar database.

The analysis revealed that 20,968 people, 5.05% of the total, were carriers of at least one type of cancer.Of those, 469 participants carried more than one type.

Of the most common genes, Mutyh (1.33%), Brca2 (0.42%) and MITF (0.37%) stood out.The frequency of carriage does not change between men and women, but several differences are observed depending on the population of the study.For example, when considering all people, Caucasians showed the highest rate (5.72%), while Asians had the lowest (3.25%).

In comparison, more than 8,900 study participants were found to be at risk of bleeding from traditional diseases, and more than 400 cases with 400 cells).

Variants associated with previous cancer diagnosis

The study also examined the clinical characteristics of carriers of the pathogenic variants compared with those who did not.In this case, significant differences were found in several aspects, such as cancer growth, age at onset of oncological diagnosis, and number of family members with a history of cancer.

In terms of age at diagnosis, variants in some genes are associated with earlier disease onset.This is the case for STK11 and DICER1, whose variants are associated with a mean age of diagnosis of 31.4 and 35.4 years, respectively.In contrast, carriers of AIP variants showed a higher mean age of diagnosis, around 70.8 years.

These differences point to the added value that genetic analysis can provide in prevention.It could not only be used to assess risk, but also to predict when the disease might manifest.This information is particularly useful for suggesting personal monitoring or measures for early diagnosis.

He re-runs the debate on genetic testing in population genetics

This study assesses the frequency of pathogenic germline variants in cancer susceptibility genes in a diverse, unselected population.The results, which showed a prevalence of 5.05%, met the action criteria set out in the clinical practice guidelines to recommend genetic testing.and supports the idea that current criteria may leave a significant proportion of individuals at risk undetected.

However, it must also be taken into account that genetic variants often do not work in isolation and that the presence of a variant does not mean that the development of a variety does not mean other molecular mechanisms that contribute to increasing or decreasing the predisposition to have cancer.

The authors raise a key question: should the scope of genetic screening for cancer be reconsidered in the general population?Genetic testing of a large portion of the population allows for early detection tailored to each individual's genetic profile.However, this strategy also requires resources for important tasks such as interpretation of delayed, uncertain variants, interpretation of variants of unknown significance, and appropriate genetic counseling.To answer this question, an extended analysis of clinical utility, cost-effectiveness, and health care systems requires the creation of an advanced storage system strategy.

Inumah g, et al.I-Pathogenic Germary Verms ehlukahlukene ngohlobo lomdlavuza.Jama.2025.Mwen-DoI: http://dx.doi.oi.oi.1001/JAMA.2025.16372

New Cleveland Clinic research finds Up to 5% of Americans carry genetic mutations linked to cancer risk