Stress, Cancer Metastasis, the P53 gene and Mindfulness
By Kathleen Helen Lisson, CLT
I have a history of skin cancer, basal cell carcinoma specifically, and every time I have an exam with my dermatologist she is burning off actinic keratosis spots on my face. Year after year, I am reminded that skin cancer is because of decades of sun exposure and the important thing is to limit excessive sun exposure, tanning beds and wear sunscreen.
After a recent visit, I wanted to dig deeper. Exactly why was I getting precancerous growths, year after year? I did a little digging and found a link between actinic keratosis and the p53, also referred to as TP53.
What is TP 53? Boutelle & Attardi state that “the TP53 tumor suppressor is the most frequently mutated gene in human cancer.” What does this gene do in our body? The researchers state that “p53 is thought to act as a tumor suppressor by serving as a cellular stress sensor… In unstressed cells, p53 is targeted by the E3 ubiquitin ligase MDM2 for degradation, keeping p53 at low levels. A variety of stress signals, including DNA damage, oncogene expression, and hypoxia, relieve p53 from MDM2 inhibition” (Boutelle & Attardi, 2021).
Chronic stress can affect the TP53 gene in our body.
How does stress affect cancer tumor development? Feng et al. state that “epidemiological studies have strongly suggested that chronic psychological stress promotes tumor development.” The researchers did a study in mice and were able to demonstrate “that the attenuation of p53 could be an important part of the mechanism by which chronic stress promotes tumorigenesis. Our results demonstrated that chronic stress decreases p53 protein levels and function in mice.” They state that “considering the critical role of p53 in preventing the initiation and/or progression of cancer, the attenuation of p53 function by chronic stress could lead to the promoting effect of chronic stress on the initiation and/or progression of cancer” (Feng et al., 2021).
Stress can also have an effect on metastatic disease.
Did your doctor speak to you about the importance of stress reduction before and after cancer surgery? Eckerling et al. state that “critical time periods, such as the immediate perioperative time frame in patients undergoing surgery, may bear a non-proportional high impact on the fate of metastatic disease” (Eckerling et al., 2021).
What is the evidence for this? Eckerling et al. state that “in breast cancer mouse models, chronic stressors did not affect growth of primary tumours but did promote their dissemination and metastatic growth” (Eckerling et al., 2021).
Why is there conflicting evidence out there? Stress can have different effects depending on when it is experienced. Eckerling et al. state that “preclinical studies can synchronize stress or stress-reducing interventions with critical periods along cancer progression that are highly susceptible to the impacts of stress. Second, conceptual and methodological difficulties in conducting clinical studies may obscure the impact of stress on cancer progression” (Eckerling et al., 2021).
From looking at these research articles, I can see the importance of stress reduction in my everyday life, to try to support the work of my body to suppress tumor development. I can also see the importance of reducing chronic stress levels after surgery, to try to reduce the risk of metastasis.
What types of stress reduction interventions have been researched? Eckerling et al. state that “multiple psychological, behavioural and physiological interventions have been used to target different aspects of stress in patients with cancer, such as:
- Massage
- Acupuncture
- Yoga
- Tai chi
- Mindfulness and
- Cognitive behavioural stress-reduction interventions.” (Eckerling et al., 2021).
What are the results? The researchers say that “such interventions were shown to reduce stress, anxiety and depression, and to improve quality of life in patients with cancer (for example, in breast cancer and melanoma)” (Eckerling et al., 2021).
Why are these results happening? Eckerling et al. state that “in breast cancer survivors:
- Yoga and tai chi reduced pro-inflammatory processes, and
- Mindfulness-based stress reduction increased the T helper 1 cell (TH1)/T helper 2 cell (TH2) ratio, decreased nuclear factor-κB (NF-κB) activity and increased anti-inflammatory signalling and gene expression of type 1 interferon” (Eckerling et al., 2021).
As a lymphedema therapist, I know that people with lymphedema as a result of cancer are concerned about possible recurrence. The good news is that there ARE ways to modify stress reduction practices like acupuncture, massage, tai chi and yoga to be safe and effective for stress reduction. The book Stress Reduction for Lymphedema, takes a look at published research on mind-body practices that may reduce the negative effects of stress in people with lymphedema. The book includes step-by-step instructions and is a must-read for people with lymphedema looking for evidence-based approaches to reduce the symptoms of stress. Find Stress Reduction for Lymphedema in paperback and kindle here: https://amzn.to/3Q862Q1
Kathleen Lisson is board certified in therapeutic massage and bodywork and is a Certified Lymphedema Therapist. She has spoken at the AVLS, FDRS, MLD UK, S4OM and NLN conferences. She is a coauthor of the Standard of Care for Lipedema in the United States and the author of six books, including Stress Reduction for Lymphedema. She lives with her husband Arun and their dog in sunny San Diego, CA. Find her on Instagram at @StressReductionForLymphedema
Resources:
Boutelle AM, Attardi LD. p53 and Tumor Suppression: It Takes a Network. Trends Cell Biol. 2021 Apr;31(4):298–310. doi: 10.1016/j.tcb.2020.12.011. Epub 2021 Jan 28. PMID: 33518400; PMCID: PMC7954925. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954925/
Eckerling A, Ricon-Becker I, Sorski L, Sandbank E, Ben-Eliyahu S. Stress and cancer: mechanisms, significance and future directions. Nat Rev Cancer. 2021 Dec;21(12):767–785. doi: 10.1038/s41568–021–00395–5. Epub 2021 Sep 10. PMID: 34508247. Retrieved from: https://www.researchgate.net/profile/Anabel-Eckerling/publication/354519586_Stress_and_cancer_mechanisms_significance_and_future_directions/links/619de75907be5f31b7b38adb/Stress-and-cancer-mechanisms-significance-and-future-directions.pdf
Feng Z, Liu L, Zhang C, Zheng T, Wang J, Lin M, Zhao Y, Wang X, Levine AJ, Hu W. Chronic restraint stress attenuates p53 function and promotes tumorigenesis. Proc Natl Acad Sci U S A. 2012 May 1;109(18):7013–8. doi: 10.1073/pnas.1203930109. Epub 2012 Apr 16. PMID: 22509031; PMCID: PMC3345015. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345015/
