Tumours: how DNA predicts disease occurrence in old age

Human DNA, along with age, gender and environment, is among the factors that play a crucial role in determining whether certain viruses can remain dormant for years in the body, contributing to the onset of cancer or other diseases in later life. This is demonstrated by the largest study ever conducted on the so-called human viriome, based on genetic traces of DNA viruses found in the blood and saliva of more than 90,000 people. The findings are published in the journal Nature by Harvard Medical School, Massachusetts General Hospital, Brigham and Women's Hospital and the Broad Institute of MIT and Harvard.

The researchers analysed genome sequencing data of individuals from three large biobanks. They then tested blood and saliva samples to measure the presence of the Epstein-Barr virus (EBV), two other human herpesviruses (HHV-6 and HHV-7), the Merkel cell polyomavirus, as well as three common ringviruses, which are present in about 90% of people throughout their lives without causing disease. In this way, they discovered that each virus presents a different pattern over the course of a lifetime. The viruses manifest themselves more rapidly during the first years of life, probably as a result of primary infection. However, the prevalence of EBV increases with age, while that of HHV-6 decreases after childhood, which could indicate greater control by the immune system over time. Similarly, the prevalence of HHV-7 decreases dramatically in adulthood. The team also found that the viral load of EBV increases in winter and decreases in summer, while that of HHV-7 shows an opposite trend. Smoking is strongly associated with a higher EBV concentration (almost double in heavy smokers compared to non-smokers), while it is associated with a lower HHV-7 viral load.

Specifically, for all seven viruses considered, men had a higher viral load in blood and saliva than women. The data then revealed 82 specific positions (loci) in the human genome associated with viral load, particularly in the Major Histocompatibility Complex, a key control centre for the immune system. Many of the genetic factors most strongly linked to viral load are related to how the immune system responds to viruses and how infected cells evade immune attack. Using a statistical technique called Mendelian randomisation, the researchers also delved into the links between viruses and certain diseases. The team found that a high EBV viral load is a direct risk factor for the development of Hodgkin's lymphoma in adulthood. However, the same correlation with multiple sclerosis was not found, despite the virus being a known disease trigger. The finding suggests that the link between multiple sclerosis and EBV depends on the immune system's response to the virus, rather than the amount of virus present.