2 Observations on cancer

Cancer is a disease that has been recognised for thousands of years with Egyptian papyrus fragments describing breast cancer as a ‘bulging mass’ in the breast with crude cauterisation used to treat superficial tumours (Sudhakar 2009). It was Hippocrates, the Greek physician (460-370 BCE), who was the first to use the term ‘karkinos’ (Greek for ‘crab’) for cancer. He used this in reference to the resemblance of the way superficial blood vessels can be drawn to the site of a tumour with the legs of a crab.

Cancer is also characterised by the malignant masses of cells often the cause of a local, visible swelling. The Greek term for swelling (‘onkos’) led to the modern word ‘oncology,’ while the Latin term (‘tumere’) has become the origin of the word ‘tumour,’ the solid mass of excessive cells associated with most cancers.

Systematic observation of cancer through the ages has helped to properly diagnose and understand the disease. In the classical period and Middle Ages these observations were quite limited to the body exterior and further insights were only developed in the Modern Age with dissection and autopsy entering medical education and practice. Physicians in the Middle Ages would sometimes remove accessible cancers surgically all in the absence of proper anaesthetics (Figure 2.1)1 but further understanding of cancer and tumours being common in many parts of the body did not emerge until the practice of dissection of bodies became acceptable in the 16th and 17th century. The British surgeon Campbell de Morgan (1811-1876) was the first to put forward the idea of the focal origin of cancer, suggesting that it could spread via the lymph nodes to other parts of the body urging early surgery to remove the cancer before it had spread (Grange, Stanford, and Stanford 2002).

Evidence

  • Cancer frequently causes recognisable ‘tumours,’ e.g. local swelling due to an excess of cells/tissue
  • Local tumours can over time spread from a local mass to a systemic disease causing further tumours growth (metastasis) throughout the body.
Clara Jacobi, a Dutch woman who in 1689 had developed a large tumor on her neck (left) which was removed surgically (right).

Figure 2.1: Clara Jacobi, a Dutch woman who in 1689 had developed a large tumor on her neck (left) which was removed surgically (right).

A deeper understanding of cancer was only gained once it became possible to study tissues and cells at the microscopic level, enabling Hanseman and Boveri to consider the ‘chromatin’ irregularities observed in the cancer cells as a cause of cancer (see below).

2.1 Linking cancer and DNA

Remarkably, some pertinent insights into the nature of cancer came about well before the discovery of the structure of DNA in 1953 by James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin.

David von Hansemann, a German pathologist, in studying mitotic figures from 13 carcinomas concluded (1890) that every single case contained examples of abnormal mitoses which showed an *asymmetric distribution of ‘chromatin loops’ (Figure 2.2. Chromatin is the complex of DNA and proteins, which forms the chromosomes but this underlying structure as well as their role as a carrier of the genetic information was unknown at the time.

Theodor Boveri, a German biologist, together with his wife Marcella, studied the process of cell division using sea urchin eggs. Interfering with cell division in these cells produced cells with aberrant chromosomes; Boveri could show that different chromosomes contain distinct ‘inheritance factors’ (1904). This allowed him to recognise chromosomes as the seat of inherited information. He also demonstrated that in some cases such chromosomes could also lead to potentially unlimited growth of these aberrant cells and that this could be passed on to daughter cells (1914))(Satzinger 2008).

Before the molecular understanding of DNA it could only be identified through staining with specific dyes which revealed these nucelar structures as "chromatin loops" - of chromosomes.

Figure 2.2: Before the molecular understanding of DNA it could only be identified through staining with specific dyes which revealed these nucelar structures as “chromatin loops” - of chromosomes.

Boveri also developed a somatic mutation theory of cancer and predicted cell-cycle checkpoints (Hemmungseinrichtungen“), tumour-suppressor genes (”teilungshemmende Chromosomen“) and oncogenes (”teilungsfördernde Chromosomen"); furthermore he suggested ‘poisons’ (including nicotine), radiation, physical insults, pathogens, chronic inflammation and tissue repair might all be linked to the development of cancer by indirectly promoting aberrant mitoses or other events that cause chromosome imbalances. He continued to explain the emergence of different tumour types within one tissue and among other things anticipated the clonal origin of tumours, the allelic loss of recessive chromosome elements, and the heritability of cancer susceptibilities. His work was widely ignored for many decades but today his predictions have been verified and explained further at the molecular level (Farrell, Hutchinsin, and Marte 2006).

2.2 Learning from populations

In order to gain further understanding of cancer and its drivers it is also useful to consider what can be learned about the disease at a population level; for example, ‘who’ might get cancer, ‘what’ type of cancer this would most likely be, ‘when’ would a cancer diagnosis be most likely?

2.2.1 Cancer Epidemiology

Epidemiologists capture and describe how diseases affect populations, e.g. the number of people affected by the disease. Looking a the epidemiology of cancer allows an appreciation of the wider importance of cancer and its impact on societies.

For example we can ask questions about the incidence rate of cancer; this relates to the number of people within a population who typically will be diagnosed with cancer in a given period of time, e.g. a year. The incidence rate in the UK is approximately 550 per 100,000, comparable to the rest of the European Union (Data and Statistics for Health Professionals 2018). For the population of the UK overall this means around 440,000 new cancer cases are diagnosed each year.

Another epidemiologically important measure for the importance of a disease is the prevalence, as this gives a measure of the number of people that currently suffer from the disease. However, for cancer this is actually not necessarily a straightforward number to estimate accurately; this is due to the fact that each cancer diagnosis brings a significant amount of uncertainty in terms of outcomes and time lines involved. For example, a cancer diagnosis could in principle lead to a cure, however, in many cases it is difficult to be certain for some time whether a patient has been cured because there is often a significant risk of disease re-occurrence. Therefore instead of ‘cure’ it is more practical to consider a surrogate marker (giving a good approximation) in the form of the 5-year-survival figure, i.e. the number of patients still alive five years after the initial diagnosis or therapy. For the UK the prevalence is such that an estimated 1.4 million patients currently live with a cancer diagnosis.

Finally, a significant proportion of patients that have been diagnosed with cancer will eventually die from the disease. The proportion of patients in a population dying due to the disease in any given period is the mortality rate.

2.3 Cancer in the United Kingdom

In the UK a total of over 330,000 patients have had a cancer diagnosis – this is equivalent to 396.2 people per 100,000 of the population. Of those diagnosed more than half will have one of just four types of cancer (breast, lung, prostate and bowel). The proportion of three most common forms of cancer for each gender is given in the table below:

Cancer Males Females
Lung 14% 14%
Bowel 12% 11%
Prostate 25% na
Breast na 30%

Overall, while there is a considerable number of different cancer types the ten most common form of cancer account for 77% of all cancers.

An important consideration is that cancer incidence is not the same across all ethnicities and may differ for different cancer types. For example, the incidence in White males and Black males is somewhat higher (316 to 488/100,000) than in Asian males (168.3 to 258.9 per 100,000). White females have a significantly higher incidence than Asian and Black women (351.0 to 358.4 per 100,000 vs. 168.4 to 249.8 per 100,000 and 215 to 322 per 100,000 respectively.

Cancer is a disease that predominately affects ageing populations and in the UK (2009-2011) with over a third (36%) of cancers being diagnosed in people aged 75 and over. There are, however, additional factors at play, for example, cancer incidence is also related to socio-economic status.

Regional differences in cancer incidence in England

Figure 2.4: Regional differences in cancer incidence in England

2.4 Cancer as a Global Challenge

This means that on a global scale and estimated 18.1 million new cases will be diagnosed each year fairly evenly affecting men and women. By 2040 this number is tough to increase to 29.5 million cases (Ferlay et al. 2019).

Cancer is a disease that is viewed with fear because of the devastating impact on individuals and families. However, from a societal point of view its impact is equally harmful. This is not only due to the high cost of treating the disease itself but also the productive years lost due to cancer related premature death or disability. In 2008 the global figure for years lost was 83 million ‘healthy years.’ This has a very significant economic consequences amounting to $895 billion (2008), or on average 1.5 percent of the world’s gross domestic product (GDP). In addition there are the high direct costs of treatment which were estimated to be $88 billion in the US alone (2011), of which 50% was attributed to primary care, 11% for drugs, and 35% for hospital visits. The biggest economic impact globally was caused by lung cancer ($188 billion), colon/rectum cancer ($99 billion), and breast cancer ($88 billion).

2.5 Explore the Numbers

The WHO/IARC website is an excellent resource through which to explore cancer epidemiology further: