Final Paper: Stress and Cancer Induction

Stress is something we all experience, with significant doses administered daily — and sometimes even hourly. In the appropriate quantity and at the right time, stress helps us meet deadlines and respond efficiently to changes in schedules. Too much stress, however, can lead to detrimental effects on the physical biology of a person; perhaps the most serious of these effects is cancer. Through understanding stress and cancer separately, I’m able to thoroughly explore their relationship and explain how stress affects — and specifically causes — the group of cancerous diseases. Although a controversial claim amongst stress scientists and cancer researchers due to dated studies and limited understanding of the topic, I argue stress plays a significant role in the process of cancer induction. I contribute to the field an analysis on Reactive Oxygen Species (ROS) as the missing link in the relationship between stress and cancer induction.

To begin, it is helpful to develop a working definition of what stress actually is. Physician Hans Selye, known as the “father of stress,” first coined the term in the mid twentieth century through experiments with lab rats. After injecting the rats with harmful substances to temporarily disable specific organs, Selye observed side-effects not directly caused by the disabled organs themselves. What he found, rather, was an indirect reaction to the substances; the rats behaved differently from what the side-effects should have caused (Selye). In other words, the reactions were based on psychological responses that in turn led to other biological responses.

Selye developed a theory for the rats’ responses called General Adaptation Syndrome. The theory is made up of three stages: “1) the alarm reaction, 2) the stage of resistance, and 3) the stage of exhaustion” (Selye). The “totality” of changes observed to have taken place during General Adaption Syndrome — as both positive and negative stress — is what Selye considered to be an accurate measurement of the amount of stress as a reaction. In other words, the magnitude of difference between the body’s natural state of readiness, or homeostasis, and the stage along the General Adaption Syndrome is what Selye considered to be an accurate measurement of stress.

Selye also discovered the initial impact stress has on the body and noted “…stress causes certain changes in the structure and chemical composition of the body…” (Selye). Although these biological changes are not direct reactions to other biological factors, they are the result of the stress coping mechanisms. He accurately paved the way for future research in this area and properly identified how “the nervous system and endocrine (or hormonal) system play particularly important parts in maintaining resistance during stress” (Selye). Richard Contrada and Andrew Baum are two such researchers who took Selye’s findings a step further in their Handbook of Stress Science: Biology, Psychology, and Health. Selye’s theories have since been confirmed and the Hypothalamo-Pituitary-Adrenal (HPA) axis has been identified as the key biological center for stress (Contrada). More specifically, the HPA axis as a whole is responsible for mediating and regulating stress response (Smith).

Now that we have a working definition of stress, we can begin to explore the primary aspects of cancer. As we already know, our bodies are made up of cells — the building blocks of life. Genetic instructions reside in every cell that tell it “when and how to grow, reproduce, and die” (“What Is Cancer?”). A cell is considered cancerous when its instructions become garbled and cause the cell to behave and reproduce “in an uncontrolled way” (“What Is Cancer?”). When a cancerous cell reproduces enough, it forms a mass of the abnormal cells called a tumor. A benign tumor comes and goes without leading to any serious health complications, whereas a malignant tumor can “spread into surrounding tissues, damaging nearby cells or organs” (“What Is Cancer?”).

Fortunately, our bodies employ specialized defense mechanisms to help keep cancerous cells from spreading throughout our bodies, all of which inherit from the immune system. White blood cells called neutrophils fight infection by moving to a specific location in a body, sticking to the invading bacteria/virus/fungi, and “swallowing up” the containment with chemicals (“The Immune System And Cancer”). Antibodies stick “to proteins on the outside[s]” of white blood cells and a damaged cell to help kill it. These antibodies can also detect damaged cells — a crucial step in any fight against cancer (“The Immune System And Cancer”). When neutrophils and antibodies are not in abundance, our bodies cannot as readily use them in response to cancerous cells. If the damaged cells are not identified early, they can spread and/or divide at a quicker rate; cancer likelihood increases when the immune system is damaged or compromised. Furthermore, cancer becomes aggressive and harder to treat as it progresses, which is why the body’s natural ability to identify and kill these cells early on is so crucial.

But this paper doesn’t focus solely on stress or cancer; it focuses on the relationship between stress and cancer. Contrada and Baum write that although there is “considerable anecdotal and ‘circumstantial’ evidence” that stress can lead to the actual induction of cancer, this specific aspect of the relationship has not been “convincingly demonstrated in human populations” (Contrada 412). The “anecdotal and circumstantial” evidence Contrada and Baum have reviewed is part of why the topic of stress and cancer induction is so controversial. Up until the mid 2000s, many studies on the relationship have indeed relied on the argument of causation. Contrada argues glucocorticoids and stress networks are important factors to consider when studying the relationship between stress and cancer. Heritable characteristics, social factors, shared environments, and other psychological variables play key roles in the development of cancer (Contrada). These factors complicate cancer studies and make the relationship much more difficult to distinguish.

Myrthala Moreno-Smith writes in Impact of Stress on Cancer Metastasis that although stress science is still a relatively new field with “only limited evidence for the role of these behavioral factors in cancer initiation,” recent studies have shed new light on the relationship. A new theory has since been introduced in an attempt to explain the complex relationship “between psychosocial factors, specifically chronic stress, and cancer progression” (Moreno-Smith). Contrary to what scientists thought a decade ago, the “strongest links to cancer progression” are not stressful events, but prolonged exposure to moods of depression or hopelessness. Strong social support, for example, has been shown to link cancer patients with improved prognoses and greater chances for survival (Moreno-Smith).

The release of dopamine in the brain during high-stress situations is a significant contributing factor to the body’s stress response; this is regulated by the nervous and hormonal systems (the HPA axis), as Seyle originally proposed. In areas where cancer induction is most likely, neuroendocrine mediators control cellular function. In the ovaries, for example, the body responds to stress by increasing levels of catecholamine, which can actually aid in the formation of precystic follicles. And in line with Contrada’s research, glucocorticoids, or “a class of steroid hormones that bind to the GC receptor” play a key role in bridging the gap between stress and cancer (Moreno-Smith). GC receptors help modulate “immune activity and inflammatory responses” (Moreno-Smith).

Perumana Sudhakaran, however, argues that “contrary to community beliefs, there has been no evident association between stress and… cancer risk in large prospective cohort studies,” which contrasts with Moreno-Smith’s admittedly minimal evidence (Sudhakaran 156). This also contrasts heavily with the research of Contrada and Baum in their Handbook of Stress Science. Sudhakaran claims stress is “thought to be more influential in the progression and recurrence of cancer than its initial onset” (Sudhakaran). In other words, Sudhakaran argues stress has more of an impact on developed cancers than it does the disease’s actual induction, although the sources Sudhakaran references in forming this claim date back to the late 1990s and early 2000s. As stated before, it isn’t until the mid 2000s that we’re able to begin quantifying the relationship between stress and actual cancer induction.

Additionally, Sudhakaran argues that stress plays a key role in affecting both human and animal tumors. “Experimental research in animals… has found that stress contributes to the initiation, growth, and metastasis of select tumors” (Sudhakaran). More importantly, stress in humans has been shown to affect “key pathogenic processes in cancer, such as antiviral defenses, DNA repair, and cellular aging” (Sudhakaran). Again, Sudhakaran argues stress has more of an impact on cancer after it is developed, though this stance obviously does not factor in research that was not yet made available. Sudhakaran points out that one study found strong evidence that “those whose mental health had suffered due to the stress of the Chinese social revolution” showed greater instances of cancer than others. This trend, however, is based solely on correlation with no explanation for causation. Sudhakaran actually debunks the theory as well: with a rise in workplace stress over the past 40 years, we should also see a rise in number of cancer diagnoses, and workers in highly developed countries where workplace stress is often higher should be of higher risk for the disease. “Nearly 70 percent of the cancer deaths occur in low and middle income countries,” however, suggesting the theory is inaccurate (Sudhakaran).

These dated studies that rely solely on causation explain why the relationship between stress and cancer induction is so controversial, and Sudhakaran’s conclusions are reasonable given the studies made available at the time. Sudhakaran properly identifies DNA damage as a significant contributing factor to cancer induction, but fails to identify the crucial link — and basis of this argument — to stress. According to a study conducted in 2006, however, oxygen-free radicals, or reactive oxygen species (ROS) caused by oxidative stress, have been shown to play a “two-faced” role in stress-induced cancer (Valko). “ROS within cells act as secondary messengers in intracellular signaling cascades,” which puts the species in a deciding position (Valko). On one side, ROS can “induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species” (Valko). On the other side, however, they can “induce and maintain the oncogenic phenotype of cancer cells” (Valko).

Before further examination of ROS, I include additional supporting evidence and explanation of how ROS actually relate stress with cancer. Dr. Doni Wilson, a natural health expert and nutritionist, begins with a definition of oxidation: the process that happens as “our bodies metabolize (or process) the oxygen that we breathe and our cells produce energy from it” (Wilson). Free radicals are molecular bi-products of this process and “interact… within our cells resulting in damage (or stress) to nearby cells, mitochondria…, and DNA” (Wilson). Free radicals are both normal and necessary, and although they can cause damage, they also stimulate repair. Oxidative stress is the phenomenon where too many free radicals are produced and they “overwhelm the repair process” (Wilson). And because “oxidative stress is an underlying cause of cancer,” controlling it can help decrease risk of developing the disease.

More importantly, Wilson also claims “oxidative stress increases when we are physically and/or emotionally stressed” (Wilson). To help balance levels of oxidation stress, Wilson suggests allowing time for daily stress remedies, such as taking breaks to exercise, meditate, talk with a friend, or enjoy any activity that can help relieve stress. In other words, relieving stress helps control the body’s oxidation functions and in turn decreases the risk for developing cancer, and visa-versa.

The relationship between emotional stress and oxidization has also been demonstrated in another study with lab rats. According to the findings of Jiankang Liu of The Journal of FASEB, a “significant increase” of oxidation in tested lab rats has been observed when subjected to anxiety-inducing stress (Liu). Test rats were taped to a surface by all four limbs whereas the control group was not. Immediately after the experiment, the brain of each rat was dissected to determine protein oxidation and degree of nuclear DNA damage. The findings from each brain in the test group were compared with those in the control group. Because oxidation is linked with DNA damage, the experiment proves “emotional stress” induces a significant rise in DNA damage severity. The study concludes “immobilization stress causes oxidative damage to lipid, protein, and DNA in… rats” (Liu). The relationship between ROS, oxidation, and aforementioned DNA damage will play a key role in bridging the connection between stress and cancer induction.

Now that we’ve established the relationship between stress and oxidation, we can continue with our discussion on the relationship between oxidation and cancer with respect to ROS. Dr. Wilson isn’t alone in supporting this relationship; a study conducted in a 2006 issue of Carcinogenesis shows how “oxidative damage to cellular DNA can lead to mutations and… play an important role in the initiation and progression of multistage carcinogenesis” (Waris). Changes in DNA encoding include “base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication, and the activation of oncogenes,” all of which may be “involved in the initiation of various cancers” (Waris).

In fact, DNA damage caused by ROS is “widely accepted as a major cause of cancer;” this specific relationship is not viewed as controversial (Waris). As we’ve discussed the importance of the immune system as it pertains to fighting cancer earlier in this paper, patients “with diseases associated with a risk of cancer” show an indication of oxidative DNA damage as various autoimmune diseases. Some of these diseases include “Fanconi anemia, chronic hepatitis, and cystic fibrosis” (Waris). Waris writes “ROS are involved both in the initiation and progression of cancer,” and that the species’ attacking the cellular DNA is entirely to blame (Waris).

ROS causes damage to oxidative DNA and proteins, tumor suppressors, and photo-oncogenes (Waris). Breast cancer, for example, is considered a result of extensive oxidative DNA base damage. To make matters worse, certain types of cancer can actually produce “significant amounts” of ROS still; such an abundance of the species will only progress the cancer further (Waris). Waris concludes that the role of ROS “in cell growth regulation is complex,” though abundance promotes mitosis and cell division (Waris).

In conclusion, stress is not only linked with cancer progression, but its induction as well. Stress leaves a very serious impact on our biological selves through affecting hormonal levels that in turn lead to cellular manipulation through oxidative stress, DNA damage, and immune system interruptions. Reactive oxygen species, a bi-product of both stress and cancerous diseases, facilitate this relationship and until now have been “the missing link.” Many sources in the field of stress science conflict when considering whether or not stress can actually cause cancer; trends obviously exist, and recent studies (when pieced together to make a whole) have been able to explicitly show causation. Strong social support has been shown to improve prognoses among cancer patients. The immune, hormonal, and nervous systems’ responses to stress can facilitate induction of cancerous cells and promote tumorous growth. I argue the strength of the relationship between stress and cancer induction and hope to finally settle the dispute between stress scientists and cancer researchers alike.

Works Cited

Contrada, Richard, and Andrew Baum. The Handbook of Stress Science: Biology,
Psychology, and Health. Springer, 2011. Print.

Liu, Jiankang. “Immobilization Stress Causes Oxidative Damage to Lipid, Protein, and DNA in the Brain of Rats.” The FASEB Journal 10 (1996). Web. 8 Dec. 2015.

Moreno-Smith, Myrthala. “Impact of Stress on Cancer Metastasis.” Future Oncol 6.12
(2010): 1863-881. PMC. Web. 3 Nov. 2015. <

Selye, Hans. The Stress of Life. New York: McGraw-Hill, 1956. Print.

Smith, Sean. “The Role of the Hypothalamic-Pituitary-Adrenal Axis in Neuroendocrine Responses to Stress.” Dialogues in Clinical Neuroscience 8.4 (2006). PMC. Web. 10 Dec. 2015.

Sudhakaran, Perumana. Perspectives in Cancer Prevention – Translational Cancer
Research. New Delhi: Springer, 2014. Print.

“The Immune System And Cancer.” Cancer Research UK. 29 Oct. 2014. Web. 8 Dec. 2015. <

Waris, Gulam. “Reactive Oxygen Species: Role in the Development of Cancer and Various Chronic Conditions.” Journal of Carcinogenesis 5.14 (2006). PMC. Web. 8 Dec. 2015.

“What Is Cancer?” American Institute for Cancer Research. Web. 6 Dec. 2015. <http://

Wilson, Doni. “5 Signs of Oxidative Stress and 7 Ways You Can Stop It.” Empowering Wellness Naturally with Dr. Doni. 2 Oct. 2015. Web. 1 Dec. 2015. <https://>.

Valko, M. “Free Radicals, Metals and Antioxidants in Oxidative Stress-Induced Cancer.” Chemico-Biological Interactions 160.1 (2006): 1-40. Elsevier. ScienceDirect. Web. 1 Dec. 2015.


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