2.3

Cancer

In developed countries the impact of cancer on health is enormous. The lifetime risk of developing cancer in the US is 42 percent for men and 38 percent for women.40 The statistics are comparable in the UK for which, according to Cancer Research UK (2016), one in two people born after 1960 will be diagnosed with some form of cancer during their lifetime.41 Not all of these people will die from cancer, however. In terms of mortality, in 2015 cancer accounted for approximately 22.5 percent of all deaths in the US, second only to cardiovascular disease. The proportion of total mortality attributable to cancer was calculated to be 29 percent for the UK based on 2011 data.42 The worldwide percentage figure for cancer deaths is 13 percent, only lower because in developing countries diseases relating to malnutrition and infection significantly contribute to premature non-cancer-related mortality.

The commonest forms of cancer worldwide are of the lung, stomach, liver, bowel and breast. At least a third of cancers are known to be associated with potentially modifiable risk factors of which smoking, physical inactivity, alcohol, diet, obesity and exposure to the human papilloma virus (HPV) (through sexual activity) are the most significant in terms of numbers of people affected.

Many people who have been offered conventional therapy for cancer will also seek complementary medical treatment. Increasingly, and perhaps more so for cancer than for other chronic diseases, the conventional medical approach in Western countries is embracing complementary treatments such as acupuncture, reflexology and visualization as part of the normal provision of care for a patient with cancer. This is very common in the context of cancer care centers or hospices. It is particularly important that those practitioners of complementary medicine who may be working in a conventional medical setting have a clear understanding of the conventional understanding of the causation of cancer and how it can be treated.

This chapter focuses on the broad principles of pathology and treatment that apply to all forms of cancer. Each type of cancer has its own particular features. More details about the most important types of cancer can be found in those later sections in which the diseases of the physiological systems in which they arise are discussed.

The pathology of cancer

The initiation of cancer

As explained in Section 1.1b, cancer is the result of cumulative mutation in mitosis (leading to genetic change of the DNA) and also additional damage to the way in which the DNA in a cell functions (epigenetic change). A cancer cell develops when this cumulative damage leads to increasingly poorly controlled growth in the daughter cell lines.

A healthy cell responds to the cells around it such that it only self-replicates in a controlled way. There are many proteins produced within the cell that control its replication. These are coded for by genes called proto-oncogenes located within the chromosomes of the cell’s nucleus. The delicate function of these replication proteins within the cell becomes disordered if the proto-oncogene becomes mutated or moved during mitosis, or if it loses its relationship to another controlling gene on a chromosome as a result of insertion of the genetic material from a virus. When the function of a proto-oncogene is altered so that cell replication is no longer so well controlled, it is then known as an oncogene.

It is increasingly recognized that epigenetic processes are key to the evolution of a cancer cell line. These processes do not involve change to the genetic code embodied by the DNA, but instead affect the way by which the DNA is repaired or replicates. Some of these involve the control of genes that provide the information that directs the manufacture of the cell tumor-suppressor proteins. Tumor-suppressor proteins have diverse roles, including the recognition and repair of damaged DNA in the nucleus (over 150 different forms of these protein enzymes have been identified). Others activate the process of apoptosis (programmed cell death) in cells that have sustained too much damage. Apoptosis is a controlled form of cellular suicide that does not involve an inflammation-inducing release of cell contents.

If tumor-suppressor genes lose their function through mutation, or the proteins they code for are inhibited in some way, cancerous multiplication of cells is more likely. One tumor-suppressor mutation in the gene coding for the protein known as p53 has been identified in up to 50 percent of all forms of human tumor, depending on type of cancer. In health p53 is activated by damaged DNA, and when activated it halts the normal process of mitosis to allow for DNA repair. It also initiates apoptosis if the DNA damage is too extensive.43

Carcinogens and viruses can inactivate tumor-suppressor proteins, and this is an example of an epigenetic change that can promote cancerous growth.

In summary, cancer cells have lost the ability for ordered growth because of changes such as the presence of oncogenes and the production of ineffective tumor-suppressor proteins. The generation of an established cancer is called carcinogenesis (literally meaning the creation of cancer). For carcinogenesis to occur, a complex series of mutations must have occurred in proto-oncogenes and the genes that code for the manufacture of tumor-suppressor proteins. These mutations and alteration in DNA control proteins may have developed over many cycles of cell division, sometimes taking years, until they eventually give rise to a cancerous growth. As cancer cells continue to multiply, more mutations may arise, and the growth can become inexorably chaotic. The cancer may eventually invade neighboring tissues. The result is an irregular mass of cells called a tumor (meaning swelling) or neoplasm (meaning new growth).

In order to sustain continued growth, tumors require a blood supply. Invasive tumors do this by secreting proteins that promote the ingrowth of new blood vessels, a process known as angiogenesis. These proteins are also the by-product of cancerous mutations.

Most mutated cells are recognized by the immune system as abnormal because they present unfamiliar patterns of proteins in their cell membranes. As a result they are removed by cytotoxic T-lymphocytes as part of the immune response. It is only those cells that slip through this protective net that develop into tumors. Some tumors effectively paralyze this protective action of the immune system by secreting immunosuppressive proteins. These contribute to the general immunodeficiency seen in some patients with cancer.

The newly mutated cancer cells need to bypass the safety net provided by the immune system. Cancer is, therefore, more likely in those people who have impaired immune systems, in those in whom the rate of spontaneous mutation of the genetic material in certain cells is higher than normal, or in those who have inherited or acquired less efficient tumor-suppressive mechanisms.

The cause of increased mutation: carcinogens

It is known that mutation occurs frequently simply as a result of natural error. Cells are dividing all the time, and some of these divisions are not perfect, resulting in a mutation in the genetic material of the daughter cells. In most cases all these defective cells are removed either by the action of diverse tumor-suppressor proteins or by the cytotoxic cells of the immune system.

However, under certain conditions the number of mutations arising in a tissue will increase, and the risk of the formation of cancerous cells will also increase. The effectiveness of the tumor-suppressive mechanisms can also be impaired by external factors impacting on the health of the DNA and the tumor-suppressor proteins. When this happens there is an increased susceptibility to the development of established cancer, as the sheer numbers of cancer cells being produced increases the risk of failure of the tumor-suppressor and immune mechanisms to eliminate every single abnormal cell.

Diverse environmental factors, including tobacco smoke, alcohol, dietary factors, ultraviolet light, chemicals in the environment, infectious microbes and drugs, have all been shown to be carcinogenic. Most of these are carcinogenic because they tend to promote mutations, either of proto-oncogenes or of tumor-suppressor protein genes, or because they impair tumor suppression directly. Also, certain viruses can insert cancer-promoting sections of DNA into the chromosome or, as described earlier, can inhibit the action of tumor-suppressor proteins. Other carcinogens, such as X-radiation and cancer chemotherapeutic agents, impair the protective action of the immune system. Table 2.3-I summarizes some of the common carcinogens and the diverse forms of cancer that can result from exposure to them.

Congenital susceptibility to cancer

It is recognized that a tendency to develop cancers may be inherited. In some cases the tendency to suffer from particular cancers can run very strongly in families. For example, there is one rare form of breast cancer that will develop in over 80 percent of the daughters of women who have been diagnosed with that cancer. This cancer develops as a result of the transmission of the BRCA1 and BRCA2 gene defects. These defects result in inefficient DNA repair mechanisms in breast and ovarian tissues. Inherited defects in the aforementioned p52 tumor-suppressor gene are also well researched and correlate with increased incidence of cancer.

In such inherited cases, there is increased susceptibility to cancer, either because of an inherited relative deficiency of the immune system, or because the cells of certain tissues are genetically more prone to mutation.

Acquired susceptibility to cancer

The susceptibility to the effect of carcinogens also depends on the health of the immune system. This is impaired in conditions that cause immunodeficiency, as described in Section 2.2c. In addition, factors such as stress and aging will also contribute to impaired immune responses, and may permit a mutated cell to continue to divide and form a malignant tumor.

The development and spread of cancer

Tumors may be considered as benign or malignant. Benign growths are areas of overgrowth of normal tissue in which the replication of the individual cells remains orderly. Common benign growths include fatty subcutaneous lumps, lipomas and leiomyomas (the muscular fibroid commonly found in the womb). Benign growths tend to be very slow growing and, because they are non-invasive, have a smooth distinct boundary that separates them from neighboring tissue. They do not spread to distant sites.

In general, the term cancer is only used to describe malignant tumors. Malignant tumors demonstrate much more chaotic growth and may contain a number of different cell lines (a state described as pleomorphic) as a result of repeated mutations. The spread of the primary malignant tumor tends to be invasive and irregular as it finds its way through the normal tissues from which it has arisen. The name cancer is derived from the Latin word for crab. This term expressed for early pathologists the claw-like growth of the cancer tissue into neighboring tissues.

The term primary cancer describes a malignant growth that is the result of local spread at the site of the original cancer cell.

Secondary, or metastatic, cancer describes new cancerous growths that have spread to other sites from the original location of the primary cancer. Secondary spread can occur by seeding of malignant cells via the lymphatic system, the circulation or across the body cavities such as the intra-abdominal space. For example, a primary lung cancer is situated within the lung, but secondary lung cancer might develop in the thoracic lymph nodes, the brain and the adrenal glands as a result of spread via the lymphatic and circulatory systems.

The effects of malignant tumors

As malignant tumors continue to grow they can exert a diverse range of symptoms. Pain is a much feared symptom of cancer, although it is not necessarily a significant cause of distress in many cases. Pain can result from the pressure of a tumor in an enclosed space, blockage of a hollow organ causing the organ to distend, and also from invasion of or pressure on nerves.

Cachexia is the term used to describe loss of appetite, weight loss and general feeling of malaise that affects many patients with advanced cancer. Nausea and constipation can also be very distressing symptoms of advanced cancer.

The immune system is often depressed in advanced cancer, partly because of the malnutrition that accompanies cachexia, and partly because of the tumor’s ability to produce immunosuppressant proteins. Moreover, if the cancer invades the bone marrow (leading to bone marrow failure), the production of leukocytes will be impaired. Immune deficiency leaves the body open to infectious diseases that may give rise to symptoms such as cough, fever and cloudy urine. These symptoms may have the characteristics of opportunistic infections.

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