Cancer often is chalked up to bad luck.
An errant epigenetic change, a buildup of DNA damage, a breakdown in the immune system — a perfect storm that tips the cellular scale from health to disease. Adding to the complexity is the fact that cancer risk varies from person to person. Factors such as family history, exposure to certain chemicals or radiation, diet and exercise all play a role.
Unfortunately, bad luck is not a realistic target for future cancer treatments.
But let’s take a step back and really think about luck. In many ways, it’s just another word for chance or, better yet, **risk** (a term with which scientists are more comfortable).
What if we could better understand a person’s baseline risk even before they are exposed to other factors that influence cancer, perhaps even before birth?
This was the focus of a recent paper we published in [_Nature Cancer_](https://www.nature.com/articles/s43018-024-00900-3). We identified two distinct epigenetic states established during development that affect lifelong cancer risk.
One state is associated with a lower risk of cancer. If cancer does develop, it is more likely to be a liquid tumor such as leukemia. The other state is associated with a higher risk of cancer; this state is more likely to cause solid tumors such as breast or lung cancers.
In some ways, the findings upend the proverbial apple cart. Cancer often is considered a disease of aging, and for good reason. As we grow older, we accumulate DNA damage and exposures that increase our cancer risk. Some of these exposures can be mitigated through lifestyle changes, while others are passed down genetically or epigenetically from our parents.
Although this all still holds true, our findings add another layer of risk predisposition to the mix by suggesting that the presence of one epigenetic state versus the other early in life sets the stage for our overall risk profile. Put another way, this work shifts our historical focus on risk in later life to one that includes risk much earlier (i.e., development).
Here’s the good news: bad luck might not be targetable for treatment but epigenetics **_are_** targetable. We’re still in the early days of exploring this phenomenon, which bridges the fields of cancer and developmental biology, but we’re hopeful that future research will provide additional insights that could help us reduce cancer risk.
_Research reported in this publication was supported by_ _Max Planck Gesellschaft (Pospisilik); the European Research Council under award no. ERC-CoG-682679 (Pospisilik); Van Andel Institute; Van Andel Institute’s Metabolism & Nutrition (MeNu) Program; the National Human Genome Research Institute of the National Institutes of Health under award no. R01HG012444 (Pospisilik and Nadeau); the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award no. R01DK132216 (Pospisilik and Schones); the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award no. R01AI171984 (Triche, Krawczyk, Prokop); the Chan Zuckerberg Initiative DAF, an advised fund of the Silicon Valley Community Foundation under award no. DI-000000287 (Triche); and the Human Frontier Science Program Long-Term Fellowship under award no. LT00441/2018-L (Panzeri). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders._