In some people, the fear of cancer rises to the level of an overt phobia. Cancerophobia is an active behavior related to the dread of cancer that can lead to repeated medical examinations without being able to be reassured for any length of time. Most of us are not overtly phobic about cancer but it is always lurking deep in our subconscious. Why is it not an active fear? Simply because in all likelihood, it isn’t imminent and we are hard-wired to fear clear and present danger. Risks and dangers far into the future don’t get as much priority in our daily fears. Examples of this from our daily life abound. For example, a study found that most people are not willing to take urgent action on climate change if it is presented as a distant threat. But if portrayed as proximal in time and place, most people are willing to act with urgency. This may seem unrelated to worrying about cancer but the underlying neurobiological mechanism is the same. So, should we worry more about cancer? George Klein, Professor Emeritus at the Microbiology and Tumor Biology Center at the Karolinska Institute in Stockholm, Sweden, has been a teacher and a researcher since the mid-1940s. He published a fascinating article in The Scientist that makes the point that approximately 1 in 3 people will be struck by neoplastic disease in his or her lifetime. But, the other side of that coin is that two out of three people remain unaffected1. Even the majority of heavy smokers who bombard their lungs with carcinogens and tumor promoters over many years remain cancer free. Pathologists have shown that virtually all men age 60 or older have microscopic prostate cancer when examined at autopsy, however, most of these micro-tumors never develop into cancer. It is also known that disseminated cancer cells are present throughout the body in most cancer patients, but only a small minority of these cells develop into secondary tumors or metastases. The rest are kept under control by the body. In other words, when it comes to getting or not getting cancer, the glass is more than half-full. So, should we just relax and not worry? That’s not a productive question to ask. A more interesting one, that may actually produce interesting answers is: What makes most people resistant to cancer? Cancer develops by either mutations or by some virus infections. We know that colon cancer, breast cancer, and prostate cancer, develop through progressive stages of mutations that ultimately cause cell division to spin out of control and proliferate wildly. So is cancer resistance simply the other side of the coin, namely lack of harmful mutations? Put in those terms, is not getting cancer simply a matter of luck? But to paraphrase Albert Einstein’s quip about quantum mechanics, evolution doesn’t play dice; it increases its odds with natural selection. It turns out that mutations, harmful or otherwise, occur all the time in all of us. But, we all (with few exceptions of genetic or pathological conditions) possess several well-known mechanisms for active resistance to cancer. The body’s anti-cancer mechanisms In a PNAS paper, George Klein identified five kinds of anti-cancer mechanisms: 1. Immunologic The first type is immunological, which applies to virus-associated cancers. For instance, researchers have compared the antibody responses of the squirrel monkey and the marmoset when infected with Herpesvirus saimiri, a virus that is endogenous to squirrel monkeys, but that the marmoset never encounters. When exposed to the virus, the marmosets, but not the squirrel monkeys, develop rapidly growing lymphomas. The researchers found a striking difference in the timing of each animal’s antibody response. In the tumor-resistant squirrel monkeys, the antibodies rose to a high level just three days after the infection, but, for the marmosets, the response took three weeks, too late to stop the virus-driven lymphoma. The dynamics of the antibody response suggest that squirrel monkeys had pre-existing memory T cells against the virus, whereas the marmosets had to develop them first before a full-blown antibody response could be mounted, a process that takes about three weeks. 2. Genetic The second mechanism Klein describes is genetic. Our cells are constantly subjected to DNA damage and there are individual variations in the efficiency of the repair mechanisms. Although, in the vast majority, these mechanisms are capable of repairing the damage quickly, some are not. An example is DNA repair deficiency called xeroderma pigmentosum. Individuals with this deficiency are highly sensitive to ultraviolet light, and even with careful protection, they develop multiple skin carcinomas due to the genetic deficiency. 3. Epigenetic The third mechanism is epigenetic, which involve changes in gene expression, rather than changes in the DNA text itself. DNA methylation is one of the key epigenetic factors involved in regulation of gene expression and genomic stability and is biologically necessary for the maintenance of many cellular functions. Genomic hypomethylation is common in both solid tumors such as prostate cancer, hepatocellular cancer, cervical cancer, as well as in hematologic cancers such as B-cell chronic lymphocytic leukemia. The next two mechanisms are, for some reason, my favorites. 4. Apoptosis or cell death As part of an intracellular defense, a cell can trigger apoptosis, or cell death, if it detects extensive DNA damage so that the cell doesn’t reproduce and spread the damage. It is the ultimate altruism on the cellular level. In some individuals, this mechanism fails. The cellular protein P53 is a tumor suppressor. When it is mutated, it increases the risk of inheriting Li-Fraumeni syndrome, a rare disease in which patients develop multiple tumors. 5. Factors in the tissue’s microenvironment The last mechanism of defense against tumors resides in the microenvironment in which tissues are embedded. Here is a striking example. The naked mole rat (NMR) and the blind mole rat (BMR), live up to 20 and 30 years, respectively, and never develop cancer. How did they pull off this trick? The naked mole rat (NMR) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. The NMR is a social species that lives in highly organized matriarchal societies. It has to force its way through narrow and often sinuous underground tunnels. The connective tissue in its skin contains a high-molecular-weight form of hyaluronic acid (HA) that makes the animal’s skin malleable. The corresponding HA in mice and humans has less than one-fifth the molecular weight. The heavy form of HA that occurs in the NMR is not only beneficial for the animal’s locomotion, it also prevents the transformation of normal cells in cell culture into cancer cells. Only after it has been removed can the NMR’s cells be transformed into cancer cells. The NMR cells also display an extreme sensitivity to contact inhibition: The cells stopped dividing when barely touching each other. Several species of the blind mole rats (Spalax judaei and Spalax golani) are common in Israel and surrounding countries. BMRs are small subterranean rodents and are distinguished by their adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 years), and resistance to cancer. In tissue culture, when overproliferation started taking place after several cell divisions, BMR cells began secreting interferon ß which triggered a massive cell suicide response (a.k.a. apoptosis). The Masada phenomenon is apparently alive and well in the Middle East. In case you conclude that it is subterranean living or the small size that protects these animals from getting cancer, think again—the blue whale is cancer free as well. So, we don’t have to live underground or go back to the ocean, where our very distant ancestors came from. So, don’t worry about cancer Rather, we can take a deep breath and relax because two-thirds of us will never develop cancer. As for the other third, don’t despair. Diagnostics and therapeutics for cancer are propagating at a rapid rate. That doesn’t mean all cancers are preventable or curable yet. But I, for one, am putting my faith in human ingenuity to one day make cancer less feared than it is today. Source
