SOPHIA YANG
Age 16 | Vancouver, BC
Genome British Columbia Award
Edited by: Megan Clemens
This study observed the link between negative thinking and mutation in the TP53 gene, commonly found to promote cancers. A content analysis showed that constant negative thoughts over long periods of time can change the way signals are being interpreted in the body and stimulate the release of compounds that prevent genes from producing proteins. Thirty-seven case studies revealed that 92.5% of TP53-mutated cancer patients had chronic negativity (>25 weeks) prior to any diagnostics, thus showing the correlation between negative thinking and carcinogenesis.
INTRODUCTION
The mind-body connection has often been disregarded and labelled as scientific quackery (Marchant, 2016) and has only begun to be studied by researchers in the last few decades (Hart, 2016) with the recent introduction of epigenetics. Epigenetic modifications are variations in gene expressions that do not alter the genetic sequence; these changes are often a result of behavioral and environmental influences. In the United States, 90% of doctor visits are for illnesses related to stress (Grayson, 2019). Although mainstream medicine is slowly becoming more accepting of the notion that the mind has an influence on the body, most institutions continue to rely on doctors recommending drugs instead of offering self care through mental healing practices (Brower, 2006). A textbook example of this connection is the placebo effect, which can have as high as a 72% recovery rate (Rankin, 2013) while their drug counterparts can have recovery rates of as little as a 1% increased difference (Hamilton, 2012). On the other side of the spectrum, the nocebo effect is when negative expectations lead to damaging health outcomes. Multiple sources have shown that noceboes have a higher effectiveness than placebos (Heid, 2019; Greville-Harris & Dieppe, 2015). Although there is now a substantial amount of research that provides evidence to a negative mind’s influence on worsening physical conditions, there is very limited information on whether or not it has the ability to promote disease (Tilan & Kitlinska, 2010; Peck, 2020).
Some of the most mysterious and widespread diseases are cancers. The list of carcinogens is constantly fluctuating, but their similarities lie in the fact that all of them are physically traceable (The Editors of Encyclopaedia Britannica, 2019). The goal of this project was to research and study the correlation between negative thinking and carcinogenesis. A study by John Hopkins University revealed that two-thirds of all adult cancer cases are caused by ‘random’ genetic mutations that induce tumor growth (Crain, 2019). This means that adults who have not been extensively exposed to carcinogens are as susceptible to developing cancer as those who have been exposed to carcinogenic agents, all due to bad luck in genetics. This phenomenon gave insight into why those who lead physically healthy lifestyles may still get diagnosed with cancer. The influence of the mind on the random gene mutation phenomenon in carcinogenesis (the initiation of cancerous cell proliferation) has never been extensively studied.
TP53 (tumor protein 53) is a tumor suppressor gene that is mutated in over 50% of all cancers (Olivier et al., 2010). The protein created from this gene is called p53, and it plays an integral role in regulating cell division, apoptosis (programmed cell death), and preventing cancerous cells from proliferating out of control. TP53 was discovered in 1979 (Jiang, 2011), and information on the factors that cause it to mutate are still being researched (Schetter & Harris, 2012). Mutation in TP53 was the focus of this study because of its frequent occurrence and competence in carcinogenesis.
Epigenetic modifications that cause mutations preventing p53 proteins from binding to and repairing damaged DNA were investigated (ScienceDaily, 2015; Ivanov et al., 2007; Sionov, 1970). Methylation is a type of epigenetic modification involving the addition of a methyl group (CH3) to DNA, altering genetic expression without changing the genetic sequence. Hypermethylation of the TP53 gene can reduce genetic expression by 90% (Saldaña-Meyer & Recillas-Targa, 2011) and prevent p53 proteins from even being produced, thus inducing carcinogenesis. Although not all people with the TP53 mutation are guaranteed to develop cancer, the likelihood of developing cancer with the mutation is over 90% (Ambry Genetics, 2020; LFSA, 2020). The direction this study takes comes from the assumption that there is an underlying influence causing these ‘random’ genetic mutations. Something that was repeatedly observed in cancer patients who lead physically healthy lives was that most exhibited pessimistic mentalities prior to any symptoms or diagnosis.
HYPOTHESIS
The hypothesis for this project is that negative thinking patterns can lead to mutation in the TP53 gene, promoting carcinogenesis. A correlation found between negative thinking and carcinogenesis would provide a better understanding of the mystery in these ‘random’ genetic mutations. Scientific evidence of a mind-body connection can also open the door to a variety of innovative diagnoses and treatment methods in medicine.
MATERIALS & METHODS
Research was first conducted by means of a content analysis using scientific journals (Saldaña-Meyer & Recillas-Targa, 2011; Burr & Northrop, 1939; Ying & Heroux, 2013; Liboff, 2004; Nikolova, 2000; Sivitz, 2000) news articles (America Psychological Association, 2012; Nature Publishing Group, 2014; El Bacha & Da Poian, 2010; Simmons, 2008; US Department of Health and Human Services, 2011; Trafton, 2016; Trafton, 2018; Wang et al., 2019), documentaries/talks (Rankin, 2013; Netflix, 2019; Leaf, 2018) and books (Pert, 1997; Lipton, 2016) to discover if there was a plausible method in which negative thinking patterns can increase DNA methylation. The other approach used in this study involved the collection of qualitative data by utilizing the constant comparative method in the form of a case study. The aim was to analyze the mental condition of cancer patients prior to any symptoms or diagnosis of their disease. The data was collected from various internet cancer associations ( CTCA, Pancreatic Cancer UK, CURE, ZRT Lab) and the content included qualitative public patient cases (Cancer Treatment Centers of America, 2020; Zembroski, 2017; Komen, 2020; Tako, 2017; Pancreatic Cancer UK, 2020). The data was further refined through the following inclusion criteria: All cases were determined to be TP53-mutated cancers by first referring to a chart of TP53-mutated type cancers (Olivier et al., 2010), then followed by thorough research done on each cancer case. Cases that did not have the TP53 mutation were not used in this study. All patients also had to have reported to be physically healthy and not extensively exposed to carcinogens prior to any symptoms or diagnosis of their disease. Common reasons for exclusion in this section were that the patient had a history of smoking or reports of previous health conditions. A total of thirty-seven cases that met the requirements were analyzed and charted in a table showing the age they were diagnosed, type of TP53-mutated cancer (including whether it was benign or malignant) and their mental condition prior to symptoms and diagnosis of cancer. Defining their mental condition relied on analyzing the case narrative and assigning them into sub-categories based on if they had a strong correlation to the following keywords: grief, sadness, stress and positivity/happiness. Data was then inputted into Google Sheets and made into graphs that provided a statistical view of how many cases were negative vs. positive and the number of cases within each sub-category of negative thinking observed.
RESULTS
Of the case studies, 92.5% (35 cases) of TP53-mutated cancer patients reported to have had a negative mentality while 7.5% (2 cases) of patients had a positive mentality prior to diagnostics. Fig.1 compares the data in a visual manner. To further refine the data, the narrative of the negative cases was analyzed and categorized. This information was made into a graph along with whether the cases were benign or malignant (See Fig.2).
Figure 1: Negative vs. Positive TP53-Mutated Cancer Cases
Figure 2: Cases of Stress, Grief, Sadness and Positivity in TP53-Mutated Cancer Cases and Benign/Malignant Occurrences
DISCUSSION
Since cases were screened to adhere with controls put in place to eliminate extraneous variables (such as extensive exposures to known carcinogens), the high rate of malignant cases indicates that a negative mentality can potentially have enough of an influence to promote aggressive cell proliferation. It is important to note that this study refers to negative thinking as a chronic occurrence (>25 weeks), and conclusions do not support short term stressors or negative thoughts to have an association with the gene mutation.
It was also observed that the two cases who had positive mindsets before they were diagnosed were much older in comparison to the other cases examined. This can mean that age may have been the driving factor to their mutation rather than their mentalities. The most common age group (43.2%) of all the cases in this study were those 34-47 years old, and all cases reported to have a negative mentality prior to diagnosis. A study done by the APA on the stress levels of people across generations found that those ages 34-47 were experiencing the most stress (American Psychological Association, 2012). Further research supported the study by finding that 63% of the people in that age range are dealing with stressful life events (such as major work deadlines, divorces, taxes and financial instability) that tend not to be as common to those in other age groups (Ipsos, 2000). This project investigated whether a negative mentality has an influence on the phenomena that random genetic mutations attribute to most adult cancer cases. Since the mean age group of TP53-mutated cancer patients who had a negative mindset prior to diagnostics were adults, the results show that a negative mentality has a distinct correlation with carcinogenesis.
Through the content analysis, it was discovered that signaling patterns (brain waves) that come from negative thinking can play a role in hypermethylation of DNA. This happens because methylation is heavily reliant on environmental stimuli, which can only be processed through mental interpretation (Moore et al., 2013). The nervous system delivers signals that give cells information about the environment, and epigenetic modifications adapt cellular biology to fit the surroundings. A pessimistic mentality will send incoherent signals that stimulate the release of stress chemicals and lead to unnecessary methylation (Lipton, 2016). This information demonstrates a plausible method in which negative thinking is linked to mutation of genes, but it does not provide the evidence to confirm that negative thinking will target the TP53 gene specifically. Since the results of the case studies show that 92.5% of patients with cancer from a TP53 mutation had chronic negativity, it provides evidence of a correlation between negative thinking and mutation in TP53.
As resources were limited to public patient cases accessed through the internet, only thirty-seven cases that fit the inclusion criteria were found. Clinical trials can provide a larger sample size, more precise results and better access to information on patient demographics, such as their socioeconomic status. A potential source of error in this study is recall bias, when study participants have the tendency to inaccurately recall or make false connections subjectively due to the knowledge they have of their outcome. To prevent this, existing qualitative data was collected systematically by taking the same set of information from each case and noting stressful life events as evidence for a patient reporting their psychological state. None of the patients were told the hypothesis of this study. Patient narratives limited observer influences on patient recall. Further controls that are better provided in longitudinal study designs can improve data accuracy.
In our Newtonian world, encouraging scientists to accept the mind-body connection will be difficult unless more research is done in the field. Before beginning this study, an extensive search was done to find existing studies that tested the mind-body connection; none investigated interactions between the mind and the random gene mutation phenomenon in cancer. This project is important in setting the foundation for future studies that can extend the investigation of the mind's prevalence in carcinogenesis. Further research on the role of mentality in disease can also have positive implications, such as discovering the role a positive mindset can play in the prevention of disease.
CONCLUSIONS
Negative thinking was found to have a correlation with mutation in the TP53 gene and carcinogenesis. Thoughts and emotions affecting the delivery of magnetic signals and having an influence on physical processes such as DNA methylation show the importance of the mind in disease. The findings of this study suggest that the phenomenon of genetic mutations inducing cancer growth is less random than once speculated, as evidence shows a negative mentality can have an underlying effect. Theories about the mind-body connection playing a role in cancer and other conditions should not be disregarded as quackery, and more time dedicated to this field have potential to uncover some of the mysteries in medicine. In the future, it would be beneficial to use this study as a basis for clinical trials, as well as conduct further research following the same study design investigating gene mutation in other genes that lead to carcinogenesis. Some big prospects include sharing the information of this study with scientists and the public to bring about a shift in the direction of modern medicine to becoming more inclusive to treatment and diagnosis innovation involving the mind-body connection.
REFERENCES
Ambry Genetics. (2020). Understanding Your Positive TP53 Genetic Test Result. Understanding Your Positive TP53 Genetic Test Result - Materials - Oncology | Ambry Genetics. http://www.ambrygen.com/material/oncology/understanding-your-results/tp53/1039.
American Psychological Association. (2012). Stress by generation. APA. https://www.apa.org/news/press/releases/stress/2012/generations.
Brower, V. (2006, April). Mind-body research moves towards the mainstream. EMBO reports. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456909/.
Burr, H. S., & Northrop, F. S. C. (1939). Evidence for the Existence of an Electro-Dynamic Field in Living Organisms. Proceedings of the National Academy of Sciences, 25(6), 284–288. https://doi.org/10.1073/pnas.25.6.284
Cancer Treatment Centers of America. (2020, March 12). Stories from Patients with Breast, Lung and Other Cancers. CTCA. https://www.cancercenter.com/patient-stories.
Crain, E. (2019, June 11). The Surprising Reason Most People Get Cancer. Women's Health. https://www.womenshealthmag.com/health/a19889751/gene-mutations-and-tumors/.
El Bacha, T., Luz, M. & Da Poian, A. (2010). Dynamic Adaptation of Nutrient Utilization in Humans. Nature Publishing Group. https://www.nature.com/scitable/topicpage/dynamic-adaptation-of-nutrient-utilization-in-humans-14232807/.
Grayson, H. (2019, April 25). Mind Body Medicine: How to Uncover the Hidden Mental-Emotional Roots of Illness. Conscious Lifestyle Magazine. https://www.consciouslifestylemag.com/mind-body-connection-health/.
Greville-Harris, M., & Dieppe, P. (2015, February). Bad is more powerful than good: the nocebo response in medical consultations. The American journal of medicine. https://www.ncbi.nlm.nih.gov/pubmed/25232716.
Hamilton, David R. (2012, November 16). The Amazing Power of the Placebo. David R Hamilton PhD. https://drdavidhamilton.com/the-amazing-power-of-the-placebo/#:~:text=Where%20you%20live%20also%20affects,10%25%20better%20than%20placebo%20injections.
Hart, P. (2016). What Is the Mind-Body Connection? Taking Charge of Your Health & Wellbeing. https://www.takingcharge.csh.umn.edu/what-is-the-mind-body-connection.
Heid, M. (2019, November 14). The 'Nocebo Effect' May Be Even Stronger Than Placebo. Medium. https://elemental.medium.com/the-nocebo-effect-may-be-even-stronger-than-placebo-428ba0f32d7e.
Ipsos. (2000, October 18). Stress Becoming A Way of Life For Canadians. Ipsos. http://www.ipsos.com/en-ca/stress-becoming-way-life-canadians.
Ivanov, G. S., Ivanova, T., Kurash, J., Ivanov, A., Chuikov, S., Gizatullin, F., … Barlev, N. A. (2007, October). Methylation-acetylation interplay activates p53 in response to DNA damage. Molecular and cellular biology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099237/.
Jiang, L. (2011, January 21). The Embryo Project Encyclopedia. | The Embryo Project Encyclopedia. https://embryo.asu.edu/pages/discovery-p53-protein.
Komen, S. G. (2020). Read Breast Cancer Survival Stories at Susan G. Komen. Susan G. Komen. https://ww5.komen.org/StoriesofInspiration.html.
LFSA. (2020). Who has LFS? Li-Fraumeni Syndrome Association. (2017, December 14). http://www.lfsassociation.org/what-is-lfs/who-has-lfs/.
Leaf, C. (2018, May 1). Thoughts can cause cancer - YouTube. https://www.youtube.com/watch?v=Z_IdlkG0-2c.
Liboff, A. R. (2004). Toward an Electromagnetic Paradigm for Biology and Medicine. The Journal of Alternative and Complementary Medicine, 10(1), 41–47. https://doi.org/10.1089/107555304322848940
Lipton, B. H. (2016). The biology of belief: unleashing the power of consciousness, matter & miracles. Hay House, Inc.
Marchant, J. (2016, March 6). You Can Heal Yourself With Your Mind (For Real). https://www.thedailybeast.com/you-can-heal-yourself-with-your-mind-for-real.\.
Moore, L. D., Le, T., & Fan, G. (2013, January). DNA methylation and its basic function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521964/.
Nature Publishing Group. (2014). Transcription factor. Nature News. https://www.nature.com/scitable/definition/transcription-factor-167/.
Netflix. (2019, February 1). Heal. https://www.netflix.com/watch/80220013?trackId=13752289.
Nikolova, P. V. (2000). Mechanism of rescue of common p53 cancer mutations by second-site suppressor mutations. The EMBO Journal, 19(3), 370–378. https://doi.org/10.1093/emboj/19.3.370
Olivier, M., Hollstein, M., & Hainaut, P. (2010, January). TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harbor perspectives in biology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827900/.
Pancreatic Cancer UK. (2020). Operable pancreatic cancer stories. Pancreatic Cancer UK. https://www.pancreaticcancer.org.uk/information-and-support/real-life-stories/patient-stories/operable-pancreatic-cancer/.
Peck, M. (2020, August 20). Connection between chronic stress and cancer: City of Hope. Cancer Treatment and Research Center. https://www.cityofhope.org/living-well/is-there-a-connection-between-chronic-stress-and-cancer.
Pert, C. B. (1997). Molecules of Emotion. Scribner.
Rankin, L. (2013, July 19). Mind Over Medicine: Scientific Proof You Can Heal Yourself - youtube.com. https://www.youtube.com/watch?v=gcai0i2tJt0.
Saldaña-Meyer, R., & Recillas-Targa, F. (2011). Transcriptional and epigenetic regulation of the p53 tumor suppressor gene. Epigenetics, 6(9), 1068–1077. https://doi.org/10.4161/epi.6.9.16683
Schetter, A. J., & Harris, C. C. (2012, May 22). Tumor suppressor p53 (TP53) at the crossroads of the exposome and the cancer genome. PNAS. https://www.pnas.org/content/109/21/7955.full.
ScienceDaily. (2015, September 2). Mutated p53 tumor suppressor protein uses epigenetics to drive aggressive cancer growth. ScienceDaily. https://www.sciencedaily.com/releases/2015/09/150902134929.htm.
Simmons, D. (2008). Epigenetic Influences and Disease. Nature Publishing Group. https://www.nature.com/scitable/topicpage/epigenetic-influences-and-disease-895/.
Sionov, R. V. (1970, January 1). The Regulation of p53 Growth Suppression. Madame Curie Bioscience Database [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK6412/.
Sivitz, L. B. (2000). Cells Proliferate in Magnetic Fields. Science News, 158(13), 196. https://doi.org/10.2307/3981307
Tako, B. (2017, October 24). New Normal: Life Before And After Cancer. Cure Today. https://www.curetoday.com/community/barbara-tako/2017/10/new-normal-life-before-and-after-cancer.
The Editors of Encyclopaedia Britannica. (2019, July 8). Carcinogen. Encyclopædia Britannica. https://www.britannica.com/science/carcinogen.
Tilan, J., & Kitlinska, J. (2010). Sympathetic Neurotransmitters and Tumor Angiogenesis-Link between Stress and Cancer Progression. Journal of oncology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874925/.
Trafton, A. (2016, March 7). MIT News Office. How cancer cells fuel their growth. MIT News | Massachusetts Institute of Technology. http://news.mit.edu/2016/how-cancer-cells-fuel-their-growth-0307.
Trafton, A. (2018, January 26). MIT News Office. New study reveals how brain waves control working memory. MIT News | Massachusetts Institute of Technology. http://news.mit.edu/2018/new-study-reveals-how-brain-waves-control-working-memory-0126.
U.S. Department of Health and Human Services. (2011, December 8). Scientists Find Genes That Influence Brain Wave Patterns. National Institute on Alcohol Abuse and Alcoholism. https://www.niaaa.nih.gov/news-events/news-releases/scientists-find-genes-influence-brain-wave-patterns.
Wang, Y.-H., Li, J.-Q., Shi, J.-F., Que, J.-Y., Liu, J.-J., Lappin, J. M., … Bao, Y.-P. (2019, November 19). Depression and anxiety in relation to cancer incidence and mortality: a systematic review and meta-analysis of cohort studies. Nature News. https://www.nature.com/articles/s41380-019-0595-x.
Ying, L., Heroux, P. (2013, August). Extra-low-frequency magnetic fields alter cancer cells through metabolic restriction. https://www.researchgate.net/publication/255691482_Extra-low-frequency_magnetic_fields_alter_cancer_cells_through_metabolic_restriction.
Zembroski, R. (2017, January 12). How Stress Caused My Cancer. ZRT Laboratory. https://www.zrtlab.com/blog/archive/stress-response-causes-cancer/.
ABOUT THE AUTHOR
Sophia Yang
Sophia Yang is a grade 11 student from Prince of Wales Secondary. She is actively involved in scientific research and likes spending time in Science World and helping with the museum’s events. While she enjoys scientific writing, she also writes a lot of fiction. In her free time, she likes long-distance running and reading giant books.