The initiation of cancer

As explained under the heading Mutation in Chapter 1.1b, cancer is the result of mutation in mitosis. A cancer cell develops when damage to the chromosomes during mitosis leads to defective control of cell growth in the daughter cells.

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 proteins within the cell is 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’.

There are other genes that are important in the development of cancer. These provide the information that codes for the manufacture of the cell tumour-suppressor proteins. Tumour-suppressor proteins have diverse roles, including the recognition and repair of damaged DNA in the nucleus. Some 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 tumour-suppressor genes lose their function through mutation, then cancerous multiplication of cells is more likely. One tumour-suppressor mutation in the gene coding for the protein known as p53 has been identified in all forms of human tumour. It is now known that, in health, p53 is activated by damaged DNA, and when activated it halts the normal process of mitosis and in doing so initiates apoptosis. It is also recognised that some viruses can inactivate tumour-suppressor proteins, another mechanism for promoting cancerous growth.

In summary, cancer cells have lost the ability for ordered growth because of the presence of oncogenes and ineffective tumour-suppressor proteins. As cancer cells continue to multiply, more mutations may arise and the growth can become inexorably chaotic and the cancer may eventually invade neighbouring tissues. The result is an irregular mass of cells called a ‘tumour’ (meaning ‘swelling’) or ‘neoplasm’ (meaning ‘new growth’).

In order to sustain continued growth, tumours require a blood supply. Invasive tumours 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 recognised 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 which develop into tumours. Some tumours effectively paralyse this protective action of the immune system by secreting immunosuppressive proteins. These contribute to the general immunodeficiency seen in some patients with cancer.

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 provide the information which codes for the manufacture of tumour-suppressor proteins and angiogenesis-promoting factors. These mutations may have developed over many cycles of cell division, sometimes taking years, until they eventually give rise to a cancerous growth. Moreover, 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, or in those in whom the rate of spontaneous mutation of the genetic material in certain cells is higher than normal.

The cause of increased mutation: carcinogens

It is known that mutation can occur simply by chance. 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. As described earlier, in most cases all these defective cells are removed either by the action of tumour-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. Such conditions are described by the term ‘carcinogenic’ (literally meaning ‘cancer causing’). 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 tumour-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 tumour-suppressor-protein genes. There are other mechanisms of carcinogenesis. Certain viruses can insert cancer-promoting sections of DNA into the chromosome or, as described earlier, can inhibit the action of tumour-suppressor proteins. Other carcinogens, such as X-radiation and cancer chemotherapeutic agents, impair the protective action of the immune system (see Q.2.3a-1). Table 2.3a-I summarises some of the common carcinogens and the diverse forms of cancer that can result from exposure to them.

Table 2.3a-I Some common carcinogens and the cancers they cause

Congenital susceptibility to cancer

It is recognised 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% 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.

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 Chapter 2.2c. In addition, factors such as stress and ageing will also contribute to impaired immune responses, and may permit a cancer cell to divide and form a malignant tumour.

The development and spread of cancer

Tumours 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 the fatty subcutaneous lump, the lipoma, and the leiomyoma (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 neighbouring tissue. They do not spread to distant sites.

In general, the term ‘cancer’ is used to describe malignant tumours only. Malignant tumours demonstrate much more chaotic growth and may contain a number of different cell forms (a state described as ‘pleomorphic’) as a result of repeated mutations. The spread of the primary malignant tumour 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 embodied for early pathologists the claw-like growth of the cancer tissue into neighbouring tissues (see Q2.3a-2).

The term ‘primary cancer’ describes a malignant growth that demonstrates 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 within 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. Lung cancer tends to metastasise by means of lymphatic spread to lymph nodes, and via the circulation to the brain and adrenal glands.

The effects of malignant tumours

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

‘Cachexia’ is the term used to describe the loss of appetite, weight loss and generally feeling of malaise which 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 tumour’s ability to produce immunosuppressant proteins. Moreover, if the cancer invades the bone marrow (leading to bone-marrow failure), then the production of leukocytes will be impaired. Immune deficiency leaves to body open to infectious diseases which may give rise to symptoms such as cough, fever and cloudy urine. These symptoms may have characterisitic of opportunistic infections.

Organ failure (e.g. failure of parts of the brain, kidney, or liver) can lead to severe life-threatening symptoms. Additional consequences of bone-marrow failure are anaemia and bleeding from thrombocytopenia.

Information Box 2.3a-I Cancer: comments from a Chinese medicine perspective

From a conventional medicine perspective, tumours result from excessive and inappropriate overgrowth of tissue cells. The underlying problem is that the genetic control of cell multiplication has become disordered and the immune system has failed to recognise and control the growth of these disordered cells.

It is important to note that the category of cancer was not one recognised in ancient Chinese medicine. Instead, the various manifestations were described according to the individual constellation of symptoms and signs presented. The terms used in the Nei Jing, for example, of ‘Intestinal mushroom’, ‘dysphagia and weight loss’, and ‘breast boil and abscess’ probably described rectal, oesophageal and breast cancer, respectively.

Modern Chinese medicine oncology dates only from the 20th century and recognises four aetiological factors: disordered emotions, poor diet, external attack by Pathogens and weakened Zang-Fu organs. The most important syndromes predisposing to cancer that these aetiological factors can lead to are considered to be Stagnation of Qi and weak Spleen and Kidney Qi. These contribute to accumulation and stasis of Blood and Fluids and the formation of tumours.

In Chinese medicine any substantial masses that do not easily move are usually regarded as manifestations of either Phlegm or Blood Stagnation (or sometimes a combination of both). Blood Stagnation is characterised by hardness and intense boring pain, with violaceous colour changes. Phlegm is more often associated with numbness, and will usually develop against a backdrop of Heat and Damp, which will manifest in other signs and symptoms. For long-standing masses to develop there is often a pre-existing state of Deficiency of Qi, as it is only healthy Qi moving freely that prevents the development of Stagnation and Phlegm.

However, some masses can manifest against a background of good Upright Qi, the strength of which is often used to determine priorities in treatment.

In contrast to the western medical approach, which is to remove the tumours, generally the focus of treatment in Chinese medicine oncology is at the root of strengthening the Upright Qi (a treatment approach known as ‘Fu Zheng’).

Cancer chemotherapy: comments from a Chinese medicine perspective

Chemotherapy and radiotherapy tend to cause preferential death of cancerous tissue, but also lead to damage and inflammation of healthy tissues. Rapidly growing tissues such as hair follicles, mucous linings and sex cells are damaged. The potential adverse effects include redness and heat of tissues in the short term, and dryness, scarring and infertility in the long term. This suggests that these treatments are intensely Heating, and exert their effects by ‘burning’ the cancerous mass. In doing so they would risk depleting Yin and Kidney Essence. For this reason complementary treatments prescribed to support chemotherapy are often focused on nourishing Yin and Essence.

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