Pregnancy protects against breast cancer by changing the epigenome

Pregnancy reduces the risk of breast cancer by reprogramming genes found in breast cells.

Previous research has shown that women who conceive before the age of 25 are 30 percent less likely to develop breast cancer. Now, new research using mice has shown that pregnancy switches off cancer-causing genes, whilst switching on others that inhibit cell division.

Dr Camila dos Santos, who led the study at Cold Spring Harbor Laboratory, New York, said 'The event of pregnancy itself changes how regions of DNA are open or closed. Think of a yo-yo. The centre of the yo-yo is what we call the nucleosome. It's a bunch of proteins that protects the DNA. When you release a yo-yo, you have a string, which represents that part of the DNA became open. And because it's open, now transcription factors can bind and either turn on or off genes. If you pull your yo-yo back, everything gets inside the yo-yo. That's what we call closed chromatin, so transcription factors cannot bind there.'

The study, published in Nature Communications, used mammary epithelial cells (MECs), or breast cells, from mice post-pregnancy. The research shows that pregnancy blocks the cancer-causing gene, cMYC, by tucking it away where is can't cause any harm.

The team overexpressed the cMYC gene and discovered that post-pregnancy MECs were resistant to the cancer-causing effects of the gene. Conversely, pre-pregnancy MECs did not show a resistance to cMYC and were still susceptible to cancer. Basically, pregnancy stops breast cells from interacting with a cancer-causing gene and doing so does not alter the normal epigenomics of pregnancy.

The research also sheds light on senescence, an irreversible mechanism that stops the cell-cycle, resulting in cells no longer dividing. Senescence is known to protect against cancer. Dr dos Santos's research has also shown that cMYC overexpression drives post-pregnancy MECs into a pre-senescence-like state, where cell growth stops and cancer development is blocked.

According to Dr dos Santos, senescent cells 'are in the grey zone, not growing or dying', meaning that the cells can either stay senescent, die, or turn cancerous. 'You have cancer genes being shut down at the same time that genes leading this cell to a kind of a precipice, like they're going to jump out and die, get turned on. We believe these signals are the key players for why these cells do not turn into cancer'.

Dr dos Santos and her team are now working with human tissue organoids to determine whether human breast cells work in the same way as those in mice. They are also transplanting cells that have been altered by pregnancy into mice that have never been pregnant with the hope to discover whether the altered cells can affect a non-pregnant environment.

This study has provided useful insights into the protective nature of pregnancy, and may lead to the discovery of novel drug targets and whether puberty or ageing can prevent cancer in the same way pregnancy does.