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The cellular basis of cancer and treatment

Risk factors and causes of cancer

Apart from specific, easily identifiable pathogens such as bacteria or viruses which can cause disease, another major cause of disease is lifestyle. Lifestyle includes the choices that we make in regards to our food, drink, whether we smoke or use drugs, certain jobs we do, even the place where we live.

The way we can measure the impact of certain lifestyle choices is by knowing risk factors. Certain diseases like cancer and coronary heart disease are associated with certain risk factors, such as smoking and obesity. On the flip side, changes in lifestyle are also associated with a decrease in risk of contracting these diseases.

A key risk factor for bowel cancer is diet. Specifically, consumption of processed and red meats has been positively correlated with the incidence of bowel cancer, while consumption of fibre from whole grains, fruit, vegetables and enough water has been negatively correlated with bowel cancer.




Cancer risk factors include heredity, ageing, different types of radiation such as UV and cosmic rays, carcinogens, air pollution and viruses (unlike HIV and influenza viruses which lead to communicable disease, some viral infections can be associated with non-communicable disease such as cancer, e.g. HPV and cervical cancer, hepatitis B and liver cancer).

You should be able to analyse graphs showing specific risk factors, such as age, sex or smoking against the incidence of disease such as lung cancer or heart disease. Pay special attention to correlations and causations i.e. when a risk factor is associated with a disease, as opposed to when a risk factor causes a disease.



For example, studies over a long period of time have shown that in fact excessive smoking causes lung cancer. On the other hand, living in urban areas is associated with an increased risk of having asthma - this does not mean living in a city causes asthma. Rather, it means it is more likely a city will be more polluted than the countryside, and it is the chemicals in the air that may cause asthma.

Cancer is primarily an environmental/lifestyle disease, with a minority of cancer types being inheritable or caused genetically. However, the effects of the environment upon cells results in clear pathways of genetic changes such as mutation as well as epigenetic changes such as methylation.



Mutations such as BRCA1 and BRCA2 increase the risk of developing some cancers such as breast and ovarian cancers, compared to non-carriers.

Mutagens are things that can cause mutations in DNA, whether at the base level or chromosome level. Many DNA mutations are the cause of cancer, therefore mutagens can be expected to also be carcinogens (things that can cause cancer).

These factors can be physical, such as UV radiation from the Sun or the radioactivity of certain chemicals such as carbon 14 (14C). They can also be chemical such as chelating agents (which bind to DNA between bases and can cause frameshifts) like ethidium bromide (mutagen), or indeed asbestos (carcinogen).




Some biological carcinogens include chemicals from the fungus Aspergillus and some bacteria.


Uncontrolled cell division in cancer

Knowledge of the cell cycle comes in very useful in the treatment of cancer. Cancerous cells divide out of control, often due to mutations in DNA which result in improper regulation of cell division. These mutations have been isolated in certain genes known as oncogenes (prior to mutation, these are termed proto-oncogenes). The best drugs to treat cancer must be efficient at targeting and killing the cancerous cells, without damaging any nearby healthy cells. 




Oncogenes whose protein products are associated with the development of cancer include Ras and Myc. Ras proto-oncogenes produce a family of related proteins that are involved in cellular signal transmission. These signals regulate cell growth and division, so hyperactivity of Ras can lead to cancer.

Myc proto-oncogene mutations lead to constant expression of the gene. It is involved in cell proliferation and can hence lead to cancer, such as Burkitt lymphoma.

When cells divide too quickly, tumour suppressor genes regulate them and give DNA an opportunity to be repaired, or for the immune response to kill the cancerous cells. If the tumour suppressor genes mutate themselves, then the probability of cancer developing increases significantly.

As such, cancer is a scenario where cell division occurs out of control, unlike in mitosis which is controlled. Therefore, many treatments targeting cancer are aimed at regulating cell division.

There are multiple separate events that lead to cancer. Often they interact with and exacerbate one 
another. Oncogenes and tumour suppressor genes are key players that regulate the cell cycle




Oncogenes promote cell growth and division, while tumour suppressor genes suppress cell division and survival. Combinations of events involving these can lead to cancer.

Oncogenes can be duplicated, or existing oncogenes can be expressed too much. Tumour suppressor genes can be inactivated. These epigenetic events can be controlled via simple methylation.




A series of cell regulation failures ends up in malignant tumours.

Sometimes, the effects are not caused by genetic expression directly. Sex hormones have been shown to be involved in the development of some types of cancer such as breast and prostate cancer, because they promote cell division. In women whose mothers got certain breast cancers, but did not have the increased susceptibility variants BRCA1 and BRCA2, higher levels of oestrogen and progesterone were found.

Knowledge of these different gene regulation pathways leading to cancer can help in finding treatments.


Diagnosis and treatment

Diagnosis

An arsenal of diagnostic techniques are employed in detecting the different forms of cancer in different parts of the body. This includes MRI, X-rays, mammography, CT scans, ultrasound, PET scans, biopsies and blood tests.

Firstly, a thorough physical examination alongside medical history are assessed.

Blood tests can check for tumour markers. These are products of tumours directly, or as a response to tumours. Other blood compounds and blood cells, as well as markers for liver and kidney health.


CT

Computerised tomography (CT) is an imaging technique used for different parts of the body, which uses X-rays processed by a computer in multiple angles to create a multiple slice picture of the brain.




The issue raised by CT is exposure to radiation which itself can cause cancer.


PET

Positron emission tomography (PET) is an imaging technique that relies on a radioactively labelled molecule (a tracer) injected into the patient to pick up metabolic signals from the body. It is used in the diagnosis of cancer metastasis.




The tracer used is a common molecule in the body such as glucosewater or urea, and following its injection into the patient, a waiting period is undertaken to allow for the molecule to disperse via the blood stream to the target location. After waiting for the required period of time, the patient is ready for scanning. The scanner picks up the signal given when the positron (like an electron but positive instead of negative) from the radioactively labelled glucose or other tracer is annihilated by the contact with an electron in its environment. It only travels up to 1 mm in the body before this happens.

Limitations of PET include exposure to ionising radiation from the tracer injected into the patient, a well as the procedure being expensive.

Basic X-rays can be used to image parts of the body and detect differences in tissue density.




Tumours such as those in lung cancer have a different density compared to the air in the lungs so are visible.

Mammograms are low intensity X-rays used on breast tissue. In order to produce a clear image, the breasts must be held still using a pressing device which can be uncomfortable.




Biopsies involve cutting off or out a tumour or tissue sample in order to identify the cell type, and thus the type of cancer present. Depending on the location of the tissue, biopsy can be performed on an outpatient basis, or require a short stay at a hospital e.g. for biopsies taken from inside the body, or an organ, etc.

Ultrasound works in the same way as that used to look at foetuses. It employs sound waves to create an image, and is carried out to see the size, structure and location of different soft tissues in the body.




Cancerous tissue draws more blood flow to itself. This can make it appear whiter on an ultrasound image. Ultrasound can be used to distinguish fluid-filled cysts from solid tumours, determine the stage of cancer, or assist during a biopsy.

MRI (magnetic resonance imaging) uses magnetic fields and radio waves to build a picture of the atomic emission and absorbance of radio energy following magnetic field exposure (nuclear magnetic resonance, NMR) which results in a picture of a patient's water and fat locations. It is carried out in a narrow chamber and can be uncomfortable, takes longer to perform than CT and is louder.




Screening and conducting genetic tests for cancer has ethical and economic considerations. The purpose of cancer screening is to detect cancer before symptoms appear. Genetic testing, on the other hand, reveals risk factors and predisposition to developing cancer. Hence, they may be common between blood relations.

Ethical considerations of screening for cancer include the avoidance of false positives that could cause great distress and further invasive procedures to investigate the finding; the availability of treatment in the case of cancer detection, as absence of suitable treatment would cause great distress; and overdiagnosing in situations where the findings would not actually pose a health risk to the patient, or the patient is already ill, old or frail and not expected to live longer than 5 years.

Cancer screening is an expensive endeavour that requires the testing and follow-up for some large sections of the populations. The benefits of screening must stack up against this cost. For example, only people at risk for certain cancers should be screened, where a suitable treatment exists to make the screening worthwhile.




Ethical considerations of genetic testing (e.g. BRCA and HNPCC) include the right of a patient to know whether their genetics poses additional risk factors of developing certain types of cancer; and the right of any blood relatives to conduct their own testing in response to this, opt out or be protected against the findings of their relative who tests positive. Economic considerations apply here as well, although not to the great extent that they do for screening.

The accuracy and safety of screening and genetic testing also play a role in whether types of screening and testing should be carried out. For example, some screening procedures like X-rays expose patients to harmful radiation, while others are not completely accurate by themselves and may lead to further screening.


Treatment

In terms of treatment, options are increasing over time and becoming more efficient and free of adverse side effects, and include surgery to remove tumours if safe to do so; radiotherapy and chemotherapy which use radiation and drugs to target cancer cells (this also targets healthy cells, causing the adverse side effects); immunotherapy which uses the body's immune system to fight cancer by introducing specific antibodies to train it to detect cancer cells; hormone-related treatment such as estrogen receptor blockers to slow down the progression of breast cancer; and complementary therapies that are used alongside the main treatments e.g. acupuncture and meditation.

Surgery is a good option if the tumour is easily accessible in the body, isn't connected to a vital organ, blood vessel or structure that would make surgery dangerous, and the benefits from removing the tumour outweigh the risks of the procedure.

Radiotherapy and chemotherapy are sometimes used together to provide the best results in terms of cancer cure, slowing down or prevention of recurrence. Ionising radiation and drugs that target different aspects of the cancer cells are used in this case. Cancer cells grow faster than healthy cells, so generic targeting involves killing them off, which also targets some of the neighbouring (or sometimes body-wide) healthy cells. This differs between patients but also between administration routes e.g. external radiation versus internal radiation from implanted radioactive metal pieces.

Side effects include fatigue, nausea, hair loss, sore mouth, itchy skin and diarrhoea.

Immunotherapy drugs are administered by injection e.g. for late skin cancer, and work by training the immune system to target cancer cells while leaving healthy cells unharmed. Side effect are similar to those of radiotherapy and chemotherapy. Immunotherapy is a newer strategy, and is being developed for different types of cancer.




Hormone related treatments work by decreasing the amount of hormones in the body that are associated with certain cancer growths. For example, the sex hormones estrogen and testosterone are associated with breast and prostate cancer, respectively. By giving patients hormone blockers or suppressors, the accelerated growth of cancer cells can be slowed down. This treatment is also helpful at preventing cancer recurrence. Side effects of diminishing hormone levels in the body include an increased risk of osteoporosis, hot flashes, impotence, fatigue and mood problems.

Complementary and alternative therapies can either be used alongside the main course of treatment that follows mainstream medicine, or as a replacement. Being outside of mainstream medicine means that some of these approaches such as chiropractice and acupuncture do not benefit from the large clinical trials and assessments that the mainstream medicine approaches undergo, and hence are seen to lack sufficient evidence to become part of mainstream medicine.

The collective experience and history of these approaches is used instead by patients in the decision-making process involved in choosing cancer treatment, and these complementary or alternative treatments have helped patients in many different ways, establishing them as often-practised on the fringes of mainstream treatments.

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