What is cancer?

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What is cancer?

Cancer is not a single illness but a collection of many diseases that share common features. Cancer is widely viewed as a disease of genetic origin. It is caused by mutations of DNA and epigenetic changes that alter gene expression, which make a cell multiply uncontrollably. However, the description and definitions of cancer vary depending on the perspective as described below.

Epidemiological perspective

Cancer is a major cause of ill health. In 2011, in the United Kingdom, there were:

434,115 new cases of cancer
159,178 deaths from cancer

There are more than 200 different types of cancer, but four of them (breast, lung, colorectal and prostate) account for over half of all new cases (Table 1.1). Overall, it is estimated that one in three people will develop some form of cancer during their lifetime. In the period 1976–2009, the age-standardized incidence of cancer increased by 22% in men and 42% in women but have remained fairly constant over the last decade (Figures 1.1 and 1.2).

Cancer incidence refers to the number of new cancer cases arising in a specified period of time. Prevalence refers to the number of people who have received a diagnosis of cancer who are alive at any given time, some of whom will be cured and others will not. Therefore, prevalence reflects both the incidence of cancer and its associated survival pattern (Box 1.1). In 2010, approximately 3% of the population of the United Kingdom (around 2 million people) are alive having received a diagnosis of cancer. Over a million Britons are cancer survivors having lived more than 10 years since being diagnosed with cancer.

The epidemiology of cancer is littered with jargon, and some of the key terms are defined in Box 1.1.

Box 1.1 Understand the Geek-speak of epidemiology

Cancer incidence is the number of new cancer cases arising in a specified period of time.
Cancer prevalence is the number of people who have received a diagnosis of cancer who are alive at any given time, some of whom will be cured and others will not.
Cancer mortality is the number of deaths due to cancer in a specific time period and defined population.
Age-specific rates. To overcome problems of different population age structures, age-specific rates for an age range (usually 5–10 years) are published. For example, age-specific incidence rates of breast cancer in women aged 50–54 years.
Standardization is used to remove the effect of a variable that you are not interested in studying (often age or gender).
Age standardized rates. This corrects the crude rates to a “standardized population”. The same “standard population” is used for all rates to allow comparisons.
Standardized ratios. Standardized incidence ratio (SIR) and mortality ratio (SMR) compare the age-specific rate in the study population with those of a control population.
Relative risk (also known as risk ratio) is the ratio of the risk of disease (e.g. lung cancer) amongst people exposed to a risk factor (e.g. smoking) to the risk amongst unexposed people (e.g. non-smokers). Data are calculated from cohort studies from which the incidence can be calculated.
Odds (as every gambler knows) is the ratio of the occurrence of an event to that of non-occurrence. If 20 out of every 100 smokers develop lung cancer, the odds are 20:80 or 1 in 4 (whilst the probability of developing lung cancer is 20/100 or 0.2).
Odds ratio compares the odds of an event in two different populations.

Table 1.1 Most frequent cancers according to age and gender

Age	0–14 yr	15–24 yr	25–49 yr	50–74 yr	>74 yr
Male	Leukaemia	Testis	Testis	Prostate	Prostate
	Brain tumour	Hodgkin lymphoma	Melanoma	Lung	Lung
	Lymphoma	Leukaemia	Bowel	Bowel	Bowel
Female	Leukaemia	Hodgkin lymphoma	Breast	Breast	Breast
	Brain tumour	Melanoma	Melanoma	Lung	Bowel
	Lymphoma	Ovary	Cervix	Bowel	Lung

Sociological perspective

People living with cancer adopt a medically sanctioned form of deviant behaviour described in the 1950s by Talcott Parsons as “the sick role”. In order to be excused from their usual duties and not to be considered responsible for their illness, patients are expected to seek professional advice and to adhere to treatments in order to get well. Medical practitioners are empowered to sanction their temporary absence from the workforce and family duties as well as to absolve them of blame. This behavioural model minimizes the impact of illness on the society and reduces the secondary gain that the patient benefits from as a consequence of their illness. However, as Ivan Illich pointed out, it also sets up physicians as agents of social control by medicalizing health and contributing to iatrogenic illness – “a medical nemesis”. Of all the common medical diagnoses, cancer probably carries the greatest stigma and is associated with the most fear. The many different ways in which cancer affects people has been explored in literature (Table 1.2).

images — **Figure 1.1** Fastest changing cancer incidences in men in the United Kingdom over the last decade. NMSC, non-melanoma skin cancer.

Experimental perspective

In the laboratory, a number of characteristics define a cancer cell growing in culture. The four features listed below are used by scientists experimentally to confirm the malignant phenotype of cancer cells:

Cancer cells are clonal, having all derived from a single parent cell.
Cancer cells grow on soft agar in the absence of growth factors.
Cancer cells cross artificial membranes in culture systems.
Cancer cells form tumours if injected into immunodeficient strains of mice (Box 1.2).

Table 1.2 Tip top cancer books

	Title	Author
1	Cancer Ward	Alexander Solzhenitsyn
2	A Very Easy Death	Simone de Beauvoir
3	Age of Iron	J. M. Coetzee
4	Cancer Vixen	Marisa Acocella Marchetto
5	One in Three	Adam Wishart
6	C: Because Cowards Get Cancer, Too	John Diamond
7	Before I Say Goodbye	Ruth Picardie
8	Illness as Metaphor	Susan Sontag
9	The Black Swan	Thomas Mann
10	Mom’s Cancer	Brian Fies
11	Coda	Simon Gray
12	Cancer Tales	Nell Dunn
13	A Grief Observed	C. S. Lewis

Box 1.2 Onco-mice

Mice have been used as a laboratory model in cancer research for a century. In the 1930s, Sir Ernest Kennaway showed that polycyclic aromatic hydrocarbons were carcinogenic by inducing skin cancers in mice. In 1969m the first inbred mice were developed that were essentially genetically identical except for gender. These strains allowed the transfer of cells and tissues between mice without rejection, as they are syngeneic (genetically identical). This has allowed the effects of experimental treatments on murine cancers to be evaluated in laboratory mice. Some inbred strains also spontaneously develop cancers (e.g. BALB/c mice frequently develop lung tumours), so the effects of cancer prevention strategies can be studied. The development of immunodeficient mice allowed the transfer and study of human cancer cells in mice without the mice rejecting the xenograft (graft between different species). The first immunodeficient mice were “nude mice”, an inbred strain that lacks a thymus gland and T lymphocytes; they are hairless because of a mutation in a linked genetic locus. Subsequently, in 1983, even more immunodeficient severe combined immunodeficiency (SCID) mice were developed that lack both T and B cells. Genetically modified transgenic mice have been manufactured by knocking out specific genes (“knockout mice”) or adding extra trans-genes, usually from different species (“transgenic mice”), to embryonic stem cells. These mice are used to elucidate the influence of individual genes on the phenotype. Finally, mice were the original source of monoclonal antibodies produced by immunizing inbred mice with the desired antigen and fusing spleen cells from the mouse with myeloma cells to yield hybridoma cells that produce monoclonal antibodies.

Histopathological perspective

Cancer is usually defined by various histopathological features, most notably invasion and metastasis, that are observed by gross pathological and microscopic examinations. Laminin staining of the basement membrane may assist the histopathologist in identifying local invasion by tumours that breach the basement membrane. In addition, a number of microscopic features point to the diagnosis of cancer:

The arrangement of tumour cells (their “architecture”) is less organized than that of their parent tissues, with heterogeneous cells of varying sizes and orientation with respect to one another despite their clonal origin (Figure 1.3).
Cancer cells have more nuclear DNA than normal cells, so they have comparatively larger nuclei, leading to a raised nuclear:cytoplasmic ratio (Figure 1.4).
Cancer cells may be multinucleated with several nuclei per cell or may have multiple prominent nucleoli (Figure 1.5).
Cancer cells divide frequently, so cancers have many mitotic figures (Figure 1.6).
Cancer cells will commonly have densely coloured or hyperchromatic nuclei with wrinkled nuclear edges (Figure 1.7).

Molecular perspective

At a molecular level, six basic steps or “hallmarks” that turn a cell into a cancer were described in 2000 by Douglas Hanahan and Robert Weinberg. In 2011, a further two “enabling hallmarks” were added that contribute to the ability of cells to acquire the six hallmarks and a further two “emerging hallmarks” required for cancer cells to continue to survive as tumours. Molecular features that identify a cancer and make it behave differently from a normal cell are described in Chapter 2. The six original properties are:

Grow without a trigger (self-sufficiency in growth stimuli).
Do not stop growing (insensitivity to inhibitory stimuli).
Do not die (evasion of apoptosis).
Do not age (immortalization).
Feed themselves (neoangiogenesis).
Spread (invasion and metastasis).

How to read a histology report

The diagnosis of cancer is most commonly established following a histopathological examination of a biopsy or tumour resection (Figure 1.8). A histopathological report should include both gross pathological features (tumour size and number and size of lymph nodes examined) and microscopic findings (tumour grade, architecture, mitotic rate, margin involvement and lymphovascular invasion). The grade and stage of a cancer are important prognostic factors that may influence therapy options (Box 1.3).

Tags: Lecture Notes Oncology

Oct 9, 2017 | Posted by admin in ONCOLOGY | Comments Off

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