The introduction is also posted on Spotify as a podcast by “Gerry at The Health Equation”

You can search Spotify for “Gerry at The Health Equation”

Or use the link below

https://podcasters.spotify.com/pod/show/gerrygaj

Below is the specific link

Gerry Gajadharsingh writes:

The Hidden Link: Stress and Cancer

“Obvious lifestyle risks such as smoking, alcohol, and obesity are well known in relation to cancer. However, what is less understood is the impact of stress and its association with cancer development. While the mechanisms of how stress affects our physiology have been researched for years, its role in cancer is now being actively explored. This shift in focus is vital, as understanding stress as a risk factor could lead to better prevention and management strategies.

For many years, clinicians have hesitated to discuss stress in relation to cancer, largely to avoid any suggestion of blame. Cancer was often considered a matter of bad luck. However, with one in two people in the UK expected to develop cancer in their lifetime, additional risk factors are finally being taken more seriously—stress being a key one.

Stress: A Subjective Reality

The challenge with studying stress is its subjective nature; it means different things to different people. As a clinician, the focus should be on how an individual’s physiology reacts to various stressors. Some people have an external locus of control, where external events significantly impact their ability to cope with stress. Others develop an internal locus of control, focusing on their internal resilience rather than external circumstances. Those who adopt this latter mindset often experience better health outcomes.

The author a doctor, associate professor of medicine and public health, married to a cancer specialist, asked his wife what causes cancer. Her answer was simple: stress. When asked why, she responded that she had observed the connection too often to ignore. Her conclusion, based on years of clinical experience and pattern recognition, highlights an issue in medicine—pattern recognition is often undervalued because it is considered anecdotal rather than scientific proof. Yet, for clinicians who have treated thousands of patients, these patterns are difficult to dismiss.

Research Findings on Stress and Cancer

A recent study published in JAMA Network Open by Stefan Ambs of the National Cancer Institute examined the relationship between stress and breast cancer. This study included 121 women (65 White, 56 Black) with primarily stage 1 and 2 breast cancer and investigated how stress impacts immune function and tumor biology.

The researchers assessed stress across four domains:

  • Daily stress (work, family, and other routine stressors)
  • Racial discrimination
  • Social isolation
  • Neighborhood deprivation

These stressors were linked to three key outcomes:

  • General immune function
  • Immune response in the tumour microenvironment
  • Tumour biology itself

One major finding was that increased stress led to higher levels of angiopoietins—substances that promote blood vessel growth into tissues. Since tumours require blood vessels to grow, this stress-induced increase is particularly concerning. Targeting angiopoietins is a key strategy in cancer therapy, and stress appears to counteract this effort.

Furthermore, stress was found to suppress the body’s natural defenses against cancer. Natural killer cells and follicular helper T-cells, which play a crucial role in destroying tumour cells, were downregulated under stress. Essentially, stress weakens the immune system, making it easier for cancer to thrive. Notably, these effects were more pronounced in Black women, possibly contributing to higher breast cancer incidence and severity in this population.

Managing Stress for Better Health Outcomes

For those diagnosed with cancer, reducing stress is easier said than done. However, research has shown that practices like yoga and mindfulness meditation can positively impact stress levels. While these methods may not be right for everyone, finding personal ways to reduce perceived stress—whether through hobbies, exercise, or social interactions—is essential. Your body, and particularly your immune system, will thank you.

Understanding and acknowledging stress as a contributing factor to cancer does not mean blaming individuals for their illness. Instead, it highlights an opportunity to develop better stress management strategies, which could ultimately improve cancer outcomes and overall well-being.

My go to tool for assessing a patient’s stress response is using capnometry and heart rate variability monitoring HRV. For the first time patients can make a connection between their thoughts and the effect of the stress thoughts and its negative impact on their breathing and nervous system. Supporting the cellular environment by increasing oxygen delivery on a cellular level and managing pH is one of the outcomes on adopting a relaxed breathing pattern. This often feeds through better balance within the autonomic nervous system, something I have blogged on many times before.”

https://www.thehealthequation.co.uk/heart-rate-variability-hrv-and-capnometry/

Medscape

F Perry Wilson MD MSCE

Think for a moment about what causes cancer. What comes to mind? The first thing that I think about is lifestyle factor stuff: smoking, alcohol intake, overweight, etc. Then I think about genetics. And then I think about bad luck — random chance and cosmic rays hitting the wrong segment of DNA and so forth. But one thing I don’t really think about, and I wonder if you do, is stress.

I am, of course, not a cancer doctor. But you know who is? My wife, the great breast cancer surgeon and expert charcuterie-board maker Niamey Wilson.

When I asked her, what factors cause cancer, she quickly and assuredly said “stress.” Why? Well, she told me, she has just noticed it too many times. A woman comes in with a new breast cancer — often without risk factors. No family history, no particular genetic risks, young. And the common thread, my wife says, is stress. She has lost track of the number of times that the individuals who come in had a recent divorce, or death of a parent, or even just an incredibly stressful work life over the past year or so. She believes in the link between stress and cancer through sheer pattern recognition.

But this week, a new study digs way deeper into that relationship, showing how stress alters the functioning of our immune systems in some very particular ways. Particular ways that just so happen to create ideal conditions for malignant cells to grow.

The paper doing all the heavy lifting for us is “Multilevel stresses and systemic and tumour immunity in black-and-white women with breast cancer” appearing in JAMA Network Open, from Stefan Ambs of the National Cancer Institute and colleagues.

It’s a study of 121 women with breast cancer (primarily stage 1 and 2), with a mean age of 56 years, comprising 65 women who describe themselves as White and 56 who describe themselves as Black.

Although formally this is a cohort study, I might refer to it as a “deep phenotyping” study, or an “-omics” study. Essentially, this study measured a slew of biomarkers in the blood, in the cancer, and in the tissue surrounding the cancer. We’re talking 92 immune-oncologic protein markers and thousands of DNA and RNA markers. It’s a powerful approach, if computationally challenging.

There’s a lot here, obviously, so I’ll give you the headline version. Broadly speaking, increased levels of stress screw up the immune system in ways that dramatically improve the environment for cancer cells. But let’s drill down a bit.

I’ll start with the immune system overall. The response to stress here is a bit complicated. In some ways, stress increases activity in the immune system — which would seem like a good thing. The immune system doesn’t only fight off bacteria and viruses, it also identifies cells that are misbehaving in your body and kills them before they can kill you. But the way stress revs up the immune system is not helpful in preventing cancer. More stress leads to higher levels of things like angiopoietins, which are substances that promote the growth of blood vessels into tissues. Targeting angiopoietins is a mainstay of cancer therapy, because tumours need blood vessels to sustain their growth, so the fact that stress increases their production is very much a bad thing.

What about the so-called “local immune microenvironment”? This is essentially the cells and tissues right around the cancer — the neighbourhood where it is growing. To see what was happening here, researchers looked at the RNA produced by the nearby cells. It’s not good. The authors found that while some immune cells, such as M1 macrophages, are ramped up, so are M2 macrophages, which actually suppress immune function. Most concerningly, cells that are particularly good at eradicating tumour cells — known as natural killer cells and follicular helper T-cells — are downregulated. If the immune system is the police force in your body, stress seems to fire the best detectives and replace them with desk jockeys who would rather eat donuts than pound leather.

It might not all be bad. Higher levels of stress led to an increase in tumour mutational burden — more genetic errors in the tumour itself. This is a bit of a double-edged sword. Higher mutational burden can mean a more aggressive cancer, but at the same time the cancers may be more susceptible to immune checkpoint inhibitor therapy — blockbuster anti-cancer drugs.

It’s worth noting that these effects were generally more pronounced in Black compared with white women, which may provide some explanation on why breast cancer incidence and severity are higher in that population.

I should also note that although racial discrimination, social isolation, and neighbourhood deprivation all had significant relationships with some pro-cancer markers, simple prolonged daily stress had the most consistent relationship across all the domains. Which makes sense, honestly. After all, things like racial discrimination, social isolation, and neighbourhood deprivation increase stress levels — that’s probably part of the reason they have such adverse outcomes on health.

A study with this many comparisons between exposures and outcomes is necessarily going to be complex to process, and I see it more as an initial shotgun approach to understanding the convoluted interplay between psychology and biology that influences cancer growth than a definitive treatment of the subject. Future studies will no doubt drill down further on these issues, perhaps revealing new anti-tumour targets.

In the meantime, what do we do? Well, it may be time to add stress to our list of cancer risk factors.

And for people with cancer, sure, it’s easy to say, “don’t stress.” It’s harder to practice it. There are studies that have evaluated yoga and mindfulness meditation in cancer, with some encouraging results. Of course, that won’t be right for everyone. Finding out what reduces that “perceived daily stress” in your own life — whether it’s yoga or golf or spending time with loved ones or playing video games — is a worthwhile endeavour. Your body, and your local immune microenvironment, will thank you.

Perry Wilson, MD, MSCE,is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator.