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Radiation and estrogen have synergistic roles in cancer development.

Published by Connealy, MD on September 19, 2024

Radiation and estrogen have synergistic roles in cancer development.

Research indicates radiation may have estrogenic effects, influencing estrogen levels and signaling in the body. This is particularly important because estrogen plays a key role in the growth and spread of cancer.

Multiple animal studies have demonstrated radiation-induced estrogenic effects which:

  • Increase estrogen concentrations in the blood
  • Increase estrogen receptor expression on cells
  • Activate cellular proliferation pathways linked to cancer (PI3K/AKT) which are also activated by estrogen

Ionizing radiation is frequently used in cancer therapy. Radiation works by damaging the cancer cell by causing direct harm to cell components, most notably, DNA. When it hits a cell, it breaks DNA strands and can lead to mutations and cell death. This can effectively kill malignant cells, but is non-selective and also harms healthy tissue. This is why many patients experience significant side effects while undergoing radiation.  

Radiation is a very nuanced topic because there are various sources and uses. For example, radiation is used in medical screenings like mammograms or x-rays and is now ubiquitous in our environment (wireless technology, radon, etc). Unfortunately, constant chronic exposure can cause cell damage, death, or abnormal replication, which can increase the risk of cancer. Radiation is a major stress on cells.

In a 2019 study, researchers evaluated breast cancer risk in childhood cancer survivors and found that radiation therapy significantly raises the likelihood of developing breast cancer, especially estrogen receptor-positive (ER+) types. The greater the radiation exposure, the higher the risk.

While the exact mechanisms are still being studied, part of this elevated risk may stem from radiation’s estrogenic effects. Ionizing radiation has been shown to act similarly to and synergize with estrogen which plays a direct role in the development of breast and other hormonally-driven cancers.

Interestingly, certain cancers that have been directly linked to radiation exposure, such as leukemia, breast cancer, lung cancer, and stomach cancer, are known to have abnormal estrogen receptor activity.

Estrogen receptors are proteins in cells that bind to estrogen and regulate gene expression and cell growth and differentiation. Many cancers show increased estrogen receptor activity, and this helps them continue to proliferate.

Animal studies have demonstrated that radiation triggers an increase in estrogen receptor alpha (ERα), resulting in elevated levels of this receptor. Researchers have discovered that radiation exposure caused persistently high levels of endogenous estradiol (a form of estrogen) in mice for up to 12 months, suggesting that radiation can boost the body’s natural estrogen production and alter receptor activity long-term. (PMID: 22381906)

While mechanisms are still being studied, radiation may increase estrogen production and receptor activity because it causes damage to DNA and cell structures. This damage stimulates a stress response, which cells address by activating repair mechanisms to build new tissue. Part of this response can involve the upregulation of ERs to increase sensitivity to estrogen, which stimulates the growth and division of new cells. This is a protective response as the body is trying to rebuild tissues after injury or damage.

However, radiation and elevated estrogen create a ‘perfect storm’ for cancer development. Damage to a cell’s DNA and structures from radiation can initiate cancerous changes. Meanwhile, high estrogen levels can stimulate the uninhibited growth of already-damaged cells, furthering cancer progression.

I find this really fascinating because we can view increased estrogen as a sort of stress response by the cell. Estrogen is sometimes considered the ‘hormone of new life’ because it helps cells proliferate. When there is injury to a tissue, estrogen often increases in order to rebuild cells and restore function. This is a good thing when it is in balance. But when our cells are chronically being damaged (from free radicals, toxins, radiation, etc.), the stress can become too much for the body, cancerous changes can take place, and estrogen can add fuel to the fire helping cancer cells to proliferate.

In this way, radiation and estrogen work together to promote cancer development: radiation damages the cell causing cancerous changes and estrogen promotes its uninhibited growth.

Other potential mechanisms:

  • Oxidative damage: Radiation generates reactive oxygen species (ROS), which cause oxidative stress and damage to cellular structures, including DNA. Estrogen, particularly estradiol, can also lead to oxidative stress when it is metabolized into reactive estrogen metabolites. Both radiation and estrogen metabolites can cause DNA mutations that may lead to cancer.
  • Endocrine dysfunction: Radiation exposure, especially in cases of therapeutic radiation (like radiation therapy for cancer), can disrupt the normal functioning of endocrine glands (such as the ovaries or thyroid). This disruption can lead to hormonal imbalances, including increased levels of circulating estrogen and decreased ‘anti-cancer hormones’ such as progesterone.
  • DNA damage repair interference: Estrogen and radiation both influence DNA repair mechanisms. Some studies suggest that estrogen signaling can interfere with effective DNA repair, while radiation causes direct DNA damage. The combination of these effects may lead to enhanced genomic instability, contributing to cancer progression.

Radiation therapy poses a fascinating paradox in cancer treatment. While it’s a powerful tool that can effectively target and destroy cancer cells, it also significantly damages healthy tissue and increases the risk of developing new cancers. I believe its estrogenic effects may play a key role in this risk.

This is why I approach treatment and screenings with caution. For instance, mammograms deliver substantial radiation to the breast, which is why they are typically recommended only after age 45. Unfortunately, many of our current treatments and prevention methods carry the potential to cause cancer themselves. This is why I’m so passionate about exploring alternative solutions—treatment should not cause disease, and it should never be worse than the illness itself.

Like everything I discuss, this topic is nuanced. Everyday we are exposed to ionizing radiation from wireless technology, medical treatments, industry, natural sources in the environment, WIFI, etc. Over the past 60 years, these exposures have increased, along with cancer rates, so I make it a priority to explore all possible contributors.

My goal is to help patients make informed decisions based on research. If you’ve been exposed to radiation, whether through x-rays, medical treatments, or other sources, there are still many ways to support the body and healthy hormone levels. Our cells are always working to repair themselves and restore balance. It’s about taking action now and providing the body with what it needs to heal.

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