A single genetic mutation may have made us more susceptible to cancer

A single genetic mutation may have made us more susceptible to cancer

It is estimated that one in five people will develop cancer in their lifetime. A sad record if we compare ourselves to other primate species, which, at least based on the available evidence, are not so prone to get cancer. Suffice it to say that out of 971 autopsies on the bodies of non-human primates who died inside the Philadelphia Zoo in Pennsylvania between 1901 and 1932, only 8 specimens were found to have neoplasms.

Our genetic heritage differs from that of chimpanzees only for 1%. And today a team from Memorial Sloan Kettering Cancer Center in New York reveals in Cell Reports that among that handful of genetic differences there is one that may have significantly increased our propensity to develop cancer compared to what happens in other primates. It may have been the price to pay for increased fertility.

What could be the reason? Researchers at the Memorial Sloan Kettering Cancer Center in New York wondered, and therefore decided to review hundreds of human genes by comparing them with their counterparts in 12 other primate species.

About differences , to be fair, there are quite a few. But one in particular has attracted the attention of scientists as it occurs in a so-called tumor suppressor gene (that is, a gene that, if it works correctly, has protective functions) and moreover in a region that is particularly conserved during the evolution of primates. The gene in question is called Brca2 and is well known in medical science because its mutations in humans considerably increase the risk of developing cancers, especially in the breast and ovaries.

New York researchers have found that human Brca2 is slightly different than that of other non-human primates: a single nitrogenous base (a single letter of the genetic code) has changed, and this is enough to change the characteristics of one of the amino acids of the corresponding protein. The amino acid alteration falls into the site (or domain) of binding with another protein (Dss1), which serves to stabilize Brca2, decreasing its affinity. In other words, the human Brca2 protein would bind less Dss1, would be more unstable and, therefore, less active in repairing DNA damage than that of chimpanzees.

The reasons why the alteration of Brca2 was selected and has become fixed in humans have not been established, but scientists speculate that they may have to do with improving fertility. There are studies, in fact, that show that women with Brca2 variants linked to an increased risk of cancer have even greater chances of getting pregnant. In short, an evolutionary compromise.

The discovery opens up many prospects for investigation and in the future it could also lead to new oncological treatments, or - who knows - to gene editing.