My team and I recently studied 36 pairs of identical twins, of which only one twin had breast cancer. These “genetic clones” had a few crucial differences. In the twin who developed the breast cancer, several hundred genes had been switched off. In a few genes, this had occurred five years before diagnosis. Such findings unlock the possibility of a diagnostic test well before the disease manifests itself, and of developing drugs that prevent — or even reverse — the cancer’s development.
Moreover, animal studies have shown that changes in stress or diet can alter the behavior and genes of future generations. As a result, it is likely that epigenetic changes can be inherited.
For example, smoking could have caused epigenetic changes in a grandparent’s DNA, effectively switching off certain anti-cancer genes. The genes would then be passed down to descendants in this switched-off state. Thus, the toxins that people ingest may not be the only relevant factor should cancer strike; the toxins that their parents or grandparents ingested could also be to blame.
Physical experiments revealing such transgenerational effects are impossible to conduct on humans, so historical or observational data must be used. One study of children in Bristol showed differences in growth depending on whether their grandfathers had smoked before the age of 11. Their bodies probably reacted defensively, adapting in the short term by changing the genes for the next few generations, or until the “danger” had passed, a so-called “soft inheritance” running in parallel to slower-acting evolutionary forces.
Fortunately, these epigenetic changes are potentially reversible. Four epigenetic leukemia drugs, which aim to switch the natural protective genes back on, are now on the market in the US. More than 40 other epigenetic drugs are being developed, not only for cancer, but also for obesity and even dementia. In the future, regular epigenetic health check-ups could become standard practice.
More than 50 years on, genes remain crucial to understanding complex diseases — especially given scientists’ ever-improving ability to alter them. The age of the gene is far from over; it has simply progressed into the age of epigenetics.
Tim Spector is a professor of genetic epidemiology at King’s College London.
Copyright: Project Syndicate