genetic inheritance influences the type of breast cancer and its prognosisaccording to Stanford Medicine research that analyzes thousands of tumors and challenges the dogma that most of these cancers arise as a result of random mutations that accumulate throughout life.
For the first time, it is confirmed that genetic sequences inherited from parents – what is known as germline genome– have an ‘active participation’ in immunosurveillance and in the types of somatic or sporadic (non-inherited) mutations that can contribute to the appearance of cancer.
That is, they have influence when determining whether cells carrying mutations potentially carcinogenic are recognized and eliminated by the immune system or go unnoticed to become incipient cancers.
The results, which could help better predict and combat breast tumors, are published in the journal Science, in an article that describes a new class of biomarkers to predict tumor progression and a way’totally new’ to understand the origins of this cancer.
Apart from a few ‘highly penetrant’ genes that confer significant cancer risk, the role of hereditary factors remains poorly understood, and most malignant tumors are assumed to result from random errors during cell division or from bad luck, says Christina Curtis, author 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 immunity,” he adds in a statement from Stanford Medicine ( USA).
Curtis explains that in 2015 his team had already postulated that some tumors are ‘born to be bad’, that is, that their malignant and even metastatic potential is determined early in the course of the disease, but these findings shed ‘a completely new light’ about how early this happens.
Variants that move the threads
Currently, only a few high-profile genetic mutations associated with cancer are used to predict cancer.
These are the BRCA1 and BRCA2 genes, which occur in one in every 500 women and confer an increased risk of breast or ovarian cancer, and rarer mutations in a gene called TP53 that causes Li Fraumeni syndrome, which predisposes to tumors of childhood and adult onset.
The new discoveries indicate 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 in different stages of the disease to find out if the subtype of each tumor correlated with the patients’ germline oncogenic sequences.
“We wanted to understand how inherited DNA can sculpt the evolution of a tumor“Details Kathleen Houlahan, another of the authors.
Among others, they found that in the initial, pre-invasive phase, a high load of epitopes – part of a molecule that will be recognized by an antibody – protects against cancer, says Houlahan.
But once they have been 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.
“Basically, there is a tug of war between the tumor and the immune cells“Curtis notes: In the pre-invasive setting, the nascent tumor may initially be more susceptible to immune surveillance and destruction. “In fact, many tumors are likely to be eliminated in 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 does not participate – of ‘excellent quality and very innovative’, since the demonstrated hypothesis 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 may contribute to the appearance of cancer, he tells Science Media Center Spain, a platform of scientific resources for journalists.