Genetic inheritance in the development of cancer is analyzed

The Genetic inheritance influences the type of breast cancer and its prognosisaccording to research from Stanford Medicine that analyzes thousands of tumors and questions the dogma that most of these cancers They arise as a result of random mutations that accumulate throughout life.

For the first time, it has been shown that genetic sequences inherited from parents – known as the germline genome – have an “active role” in immunosurveillance and in the types of somatic or sporadic (non-inherited) mutations that can contribute to the development of cancer.

That is, explains the EFE agency, they have influence when determining whether the cells carrying Potentially carcinogenic mutations are recognized and eliminated for him immune system or go unnoticed and become early cancers.

The findings, which could help to better predict and combat breast tumors, are published in the journal “Science” in an article describing a new class of biomarkers to predict tumor progression and a “completely new” way of understanding the origins of this cancer.

Apart from a few “highly penetrant” genes that confer a significant risk of cancer, the role of hereditary factors remains poorly understood, and most malignant tumors are assumed to be the result of random errors during cell division or bad luck, he says. Christina Curtisauthor of the work (only 5-10% of breast cancer is considered hereditary).

“This would imply that the onset of a tumor is random, but that is not what we observed. On the contrary, we discovered that the path to tumor development is limited by hereditary factors and by immunity,” he added in a statement from Stanford Medicine.

Curtis explains that in 2015 his team had already postulated that some tumors are “born to be bad” – that is, their malignant and even metastatic potential is determined early in the course of the disease – but these findings shed “a whole new light” on how early this happens.

Genetic variants

Currently, only a few high-profile cancer-associated genetic mutations are used to predict cancer.

It is about the genes BRCA1 y BRCA2which occur in one in every 500 women and confer a higher risk of breast or ovarian cancer, and rarer mutations in a gene called TP53 that cause Down syndrome The Fraumeni, which predisposes to tumors of childhood and adult onset.

The new findings suggest that there are dozens or hundreds of additional genetic variants—identifiable in healthy people—that “pull the strings” that determine why some people remain cancer-free throughout their lives and others do not.

The researchers studied almost 6,000 breast tumors at different stages of the disease to determine whether the subtype of each tumor correlated with the oncogenic sequences in the patients’ germline.

“We wanted to understand how inherited DNA can shape the evolution of a tumor,” said Kathleen Houlahan, another of the authors.

Among other things, they found that in the initial, pre-invasive phase, a high epitope load—part of a molecule that will be recognized by an antibody—protects against cancer, Houlahan says.

But once forced to fight the immune system and devise mechanisms to overcome it, tumors with a high load of germline epitopes are more aggressive and prone to metastasis. The pattern, he concludes, is reversed during tumor progression.

“There’s basically a tug-of-war between the tumor and the immune cells,” Curtis says: In the preinvasive environment, the nascent tumor may initially be more susceptible to immune surveillance and destruction. “In fact, many tumors are likely eliminated this way and go undetected.”

However, “The immune system does not always win“and some tumor cells may not be eliminated.

Ramón Salazar, Head of Medical Oncology and general director of the Catalan Institute of Oncology, believes that this is a study – in which he did not participate – of ‘excellent quality and very innovative’, since the hypothesis demonstrated breaks a paradigm.

For the first time, it has been discovered that inherited genetic makeup has an influence on immunosurveillance and on the types of somatic or sporadic mutations that can contribute to the appearance of cancer, he told Science Media Centre Spain, a scientific resource platform for journalists.