The Science of Cancer
- What is the scientific basis of cancer?
- How and why does cancer occur?
- Are there any known causes of cancer?
- What is the link between genes and cancer?
- Why has my pet developed cancer?
- Is cancer related to breed?
- Why does cancer affect certain breeds more than others?
- What is screening for cancer?
- What is a risk factor?
- What does risk mean?
- How do veterinary surgeons, researchers and doctors think about risk?
- How is the effect of a risk factor in an observational study expressed?
- What are cancer statistics?
What is the scientific basis of cancer?
Cancer begins with the basic unit of life for the body: cells. Every cell of the body is normally under very strict control with a defined life span and role. A group of cells forms a tissue and a group of tissues forms an organ in the body. Cells normally divide and grow to form new cells as the body needs them. When cells grow old and die, new cells take their place.
This process may go wrong when the genetic material (DNA) of a cell becomes damaged or changed, producing mutations that affect normal cell growth and division. When this happens, new cells are formed that the body does not need or, alternatively, old cells do not die as they normally should through programmed cell death (apoptosis). These extra cells can form a mass of tissue called a growth or tumour.
How and why does cancer occur?
Cancer results when changes occur in genes that control normal cell division and death (called mutations). Very occasionally, a cell acquires the ability to divide and grow outside this normal control and a cancer develops. This happens when several genes within a cell change or mutate.
Mutations occur in all of us all the time; indeed, without mutations, evolution would not occur. Most of the time, these mutations come to nothing as they are repaired, or do not change the function of a cell, but occasionally they cause the cell to go wrong and develop into cancer.
Genetic changes, or mutations, may result from environmental or lifestyle factors, such as exposure to sunlight (ultraviolet radiation) or carcinogens (cancer-causing substances) or they may be inherited (from one or both parents).
However, having an inherited gene alteration does not always mean that cancer will develop, just that the risk of developing cancer is increased.
Most forms of cancer are sporadic, meaning that there is no inherited cause of the cancer.
Are there any known causes of cancer?
For an increasing number of human cancers, a cause has been identified. Some of the known risk factors include smoking (lung cancer), certain viruses (cervical cancer) and ultra-violet sunlight (skin melanoma).
In addition, certain genes that are present in families have been identified.
Cancer results when changes occur in genes that control normal cell division and death.
- Substances that cause DNA mutations are called mutagens.
- Mutagens that cause cancer are called carcinogens.
In dogs and cats, there are only a few known risk factors for cancer.
In cats, infection with feline leukaemia virus (FeLV) can be a trigger for some types of cancer (lymphoma and leukaemia). However, not all cats that are infected with FeLV will develop cancer and, conversely, not all lymphomas in cats are induced by FeLV infection.
Another example of a cancer, for which there is a known cause, occurs in white-faced cats that are exposed to a lot of sun. The relatively hairless pink areas of the ear tips, eyelids and nose are prone to sunburn. As a result of excessive exposure to the sun, this can progress to a type of skin cancer called squamous cell carcinoma.
What is the link between genes and cancer?
In people, there are a number of recognised syndromes where there is an inherited predisposition to cancer, often due to a defect in a gene that protects against tumour formation. Examples include: Certain inherited mutations in the genes BRCA1 and BRCA2 that are associated with an elevated risk of breast cancer and ovarian cancer. Individuals with Down syndrome have an extra chromosome 21 and are known to develop malignancies such as leukaemia and testicular cancer.
Why has my pet developed cancer?
As in human medicine, it often cannot be explained why one pet develops cancer and another does not. Research has shown that certain risk factors increase the chance that a person will develop cancer. It is likely that many of the most common risk factors for cancer in people also affect our pets, including age, sunlight (ultraviolet radiation), certain chemicals, some viruses, certain hormones, poor diet, lack of physical activity, being overweight or a family history of cancer.
Current research is looking at methods of identifying specific causes of cancers in dogs and cats, and this may lead to novel ways of treating them. More importantly, as the specific causes become known, specific ways of preventing that cancer may be possible.
Several factors may act together over time to cause normal cells to become cancerous. When thinking about the risk of cancer remember that not everything causes cancer. Having one or more risk factors does not mean that an individual will get cancer. Some individuals are more sensitive than others to the known risk factors.
One of the most important risk factors for cancer is growing older. Most cancers occur in older pets although pets of all ages can get cancer. This means that as our pets are living longer, the incidence of cancer is rising. It is now estimated that 1 in every 2 people will be affected by cancer in their lifetime although more people are more likely to survive cancer now than ever before. It has been reported that about 1 in every 2 or 3 dogs and about 1 in 4 or 5 cats may be affected by cancer in their lifetime.
In the 2004 purebred dog health survey, 1 in 4 dogs died due to cancer from 1994 to 2004 (http://www.thekennelclub.org.uk/). The median age of diagnosis of cancer was 8 years in a survey of 36,006 live dogs with 22,504 conditions in total. The median age at death due to cancer was 10½ years in a survey of cause of death for 15,881 dogs from 1994 to 2004.
In a survey of cause of death in UK cats, cancer was the second most common cause of death after trauma overall and most common reason for euthanasia. Pang and Argyle 2016 32% of cats over 10 years will die of cancer 1 in 3 dogs will develop cancer.
Is cancer related to breed?
Certain breeds of dog appear to be susceptible to specific tumours (see table below). This may be related to the characteristics of the breed or due to a genetic predisposition. However, most cancers are not inherited and truly hereditary cancers (those that are passed down in certain family lines) tend to be rare in dogs.
Bone cancer is more common in giant and large breeds such as Great Danes, Irish Wolfhounds, Rottweilers, and St Bernards. This is thought to be related to the rapid growth characteristics of the adolescent pup although there is also evidence for a genetic susceptibility in some of the giant breeds. Boxers have a higher incidence of skin and brain tumours. Bernese mountain dogs suffer from a variety of malignant cancers that tend to affect a younger age group than other dogs as a whole. Similarly, Flat-coated Retrievers tend to have a relatively high incidence of sarcomas that behave more aggressively than in other breeds of dog.
These and other breed related tumours such as mast cell tumours in golden retrievers are highly suggestive of a widespread genetic susceptibility for the specific cancer associated with the breed.
Table of breed risk of developing a particular type of cancer.
|Type of cancer||Breeds with an elevated risk of developing this cancer|
|Histocytic sarcoma or Malignant Histiocytosis||Bernese mountain dog, flat-coated retrievers|
|Osteosarcoma (bone cancer)||Large breeds such as Rottweiler, great Dane, Irish wolfhound, greyhound, Saint Bernard, Doberman, German shepherd, Irish setter, golden retriever, Borzoi, Leonberger|
|Haemangiosarcoma (blood vessel tumours)||German shepherd, golden retriever|
|Mast Cell Tumour (Skin tumours)||boxer, bull dog, bullmastiff, Boston terrier, Staffordshire bull terrier, Rhodesian ridgeback, Weimarana, Labrador retriever, beagle, golden retriever|
|Lymphoma/leukaemia||boxer, bull mastiff, basset hound, Saint Bernard, Scottish terrier Airedale terrier, Bouvier des Flandres, Labrador retriever|
|Melanoma||Chow Chow, golden retriever, Pekingese, poodle, Schnauzer, Scottish terrier, cocker spaniel|
|Mammary tumours||poodles, spaniels, Puli, English setter, pointer, dachshund, German shepherd, Maltese terrier, Yorkshire terrier|
|Brain tumour||golden retriever, boxer|
|Adapted from Dobson J (2013), IRSN Vet Sci 2013, 941275, Published online Jan 17, 2013, doi: 10.1155/2013/941275 available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658424/ as Open Access.|
Why does cancer affect certain breeds more than others?
Most cancers develop because of changes in genes (mutations). A normal cell may become a cancer cell after a series of gene changes occur. Some gene changes that increase the risk of cancer are passed from parent to offspring. These changes are present at birth in all cells of the body. While it is uncommon for cancer to run in a family, certain types of cancer do occur more often in some families than in the rest of the population. For example, cancers of the breast, ovary, prostate, and colon in people.
Several cases of the same cancer type in a family or line of pedigree dogs may be linked to inherited gene changes, which may increase the chance of developing cancers. However, environmental factors may also be involved.
If you think your pet may have a pattern of a certain type of cancer in the line, you may want to talk to your veterinary surgeon about ways to detect cancer early should it develop in your pet. You may also want to ask about genetic testing. These tests can check for certain inherited gene changes that increase the chance of developing cancer. However, inheriting a gene change does not mean that your pet will definitely develop cancer. It means that your pet has an increased chance of developing the disease.
What is screening for cancer?
Some types of cancer can be found before they cause clinical signs. Checking for cancer (or for conditions that may lead to cancer) in individuals who do not have signs is called screening.
Screening means testing for early stages of a disease before an individual has any clinical signs or symptoms. Screening tests are not perfect and have some risks. For screening to be useful the tests need to:
- Be reliable at picking up cancers or abnormalities that could lead to cancer
- Do more good than harm to individuals being tested (i.e. potential benefits outweigh the risks).
The UK has 3 screening programmes for people:
- Bowel cancer screening using the faecal occult blood test
- Breast cancer screening using mammography
- Cervical cancer screening using smear tests for a virus called high risk human papilloma virus (HPV)
Screening may help your vet find and treat some types of cancer early. Generally, cancer treatment is more effective when the disease is found early. However, there is currently no effective genetic or blood test that is a reliable screening tool for the diagnosis of cancer in dogs or cats.
Regular physical examinations, laboratory testing and imaging studies are the best tools that vets have for the early diagnosis of cancer. Most vets recommend annual or biannual health checks for your pet although this will vary be breed and age of your pet. These will help identify any abnormal growths as early as possible. Also, as the pet owner, you are the person who knows your pet best and if you feel that there is just something that is not quite right about your pet, be persistent in getting a diagnosis.
An important area of current research uses dogs that are trained to detect disease in people. This is based on the dogs’ ability to detect minute odour traces created by diseases. Dogs can identify cancer in urine samples from people and we hope that one day this may be applied to the diagnosis of cancer in our pet animals species.
There are also some studies currently taking place to use cancer detection dogs to detect cancer in our pet dogs. One study is taking urine samples from healthy dogs without urinary tract abnormalities and from dogs with urinary transitional cell carcinoma or non-malignant urinary tract disease to see if the detection dogs can identify the samples with cancer.
What is a risk factor?
A risk factor is something that is associated with an increased risk of disease or death. However, a risk factor is not necessarily a cause of disease. Just because a cancer is associated with something doesn’t mean it is the cause.
For example, being old cannot be said to cause cancer, but older pets are more at risk of developing cancer because they have experienced more cell damage and exposure to potential carcinogens during their lifetime.
Having a risk factor does not mean that your pet will get cancer just as not having a risk factor does not mean that your pet will not get a cancer.
What does risk mean?
Researchers describe risk as the estimated chance of developing a disease during a certain time period, such as within the next 5 years or during a lifetime. People perceive risk as the probability of something happening, such as their pet developing cancer.
Most people are concerned about the chances of their pet developing cancer as an individual or personal risk. What you consider your pet’s personal risk may be influenced by what you have heard from your veterinary surgeon, the media and from your family and friends.
Many people view their pet’s risk of developing cancer as being higher or lower than it is due to the influence of these various sources of information.
How do veterinary surgeons, researchers and doctors think about risk?
When veterinary surgeons talk about risk they are thinking about numbers. Cancer risk in people is based on numbers of reports of cancer from medical facilities into a central registry. These reports count the total number of people who are diagnosed with a cancer in the United Kingdom.
In veterinary medicine, there are very few sources of accurate information about cancer prevalence/incidence estimates in animals as we do not have an animal cancer registry and prospective cohort studies are very expensive and rarely carried out.
Human cancer registries also provide information about how many men or women are diagnosed, and their age and race and response to treatment. The risk numbers that come from these types of information may be presented as relative risk (RR) or absolute risk (AR). In human medicine, clinical trials are used to test the effectiveness of treatments and there is much more information available than in veterinary medicine.
Veterinary surgeons can look at exposure factors that may affect cancer risk using observational studies. They draw conclusions about how these and other specific factors affect cancer risk by looking at groups of animals who have a certain risk factor and those who do not. Veterinary surgeons then look at how many individuals in the two groups are diagnosed with cancer.
By comparing how many animals in each of these groups develop cancer, veterinary surgeons are able to estimate relative risk (RR) – that is the risk that one group will get cancer compared to another group. This type of research is becoming increasingly more available for pets with more and more peer-reviewed scientific publications coming out all the time.
Veterinary surgeons can study exposure factors that may affect cancer risk using cross-sectional studies. This type of research is becoming increasingly more available for pets with more and more peer-reviewed scientific publications coming out all the time. Ideally these will be followed up with clinical trials to test different treatments for specific cancer types.
How is the effect of a risk factor in an observational study expressed?
The effect of a risk factor is often expressed as a relative risk (RR). In epidemiology (the study of health and disease status in populations of animals or people rather than individual animal medicine), relative risk is the risk of developing a disease relative to exposure to a risk factor.
Relative risk is expressed as a ratio of the probability of disease occurring in a group exposed to a certain risk factor compared to the probability of disease occurring in a group not exposed to the same risk factor. Exposure may mean being exposed to a pesticide, being a certain breed or having been vaccinated with a particular antigen (as part of a pathogen or disease-causing agent).
Another term for the relative risk is the risk ratio: it is the ratio of the risk in the exposed group or population divided by the risk in the unexposed group or population. For example, a RR of 3.0 for lung cancer associated with smoking in a study means that smokers were 3 times more likely than non-smokers to develop lung cancer. While a RR of 3 sounds high, the absolute risk is 1 case of lung cancer for every 10,000 smokers and this is very small.
How is the effect of a risk factor expressed in a survival study? In a study that looks at the survival of cases with a disease, it is the time to event (death or recurrence of disease) that is the focus. Using the statistical methods of survival analysis, the hazard ratio (HR) is estimated instead of the RR and average or median survival times can be compared between those individuals exposed to one treatment compared to another treatment.
Median survival time (MST) is the time, often expressed as the number of days, months or years, when 50% of the patients are still alive. MST s can be used to compare individuals exposed to one treatment compared to another treatment or no treatment.
One study that used survival analysis for cats with oral squamous cell carcinoma (OSCC) showed that whether the cat received non-steroidal anti-inflammatory (NSAID) therapy after surgery was associated with survival. The hazard ratio was 2.2 (95% confidence interval: 4.8 – 10.2), meaning that a cat that did not receive post-operative NSAID therapy was more than twice as likely to die earlier due to its tumour than cats that did receive a NSAID. This HR is an important estimate of the prognosis for a cat with an OSCC.
What are cancer statistics?
When we talk about cancer we often use big words such as prevalence, incidence and survival.
- Prevalence is the total number of cases at any one time.
- Incidence is the number of newly diagnosed cases during a specific time period.
- Mortality is the number of deaths during a specific time period, sometimes expressed as a proportional mortality rate. Mortality can also be expressed as a case fatality rate.
- Survival is the proportion of patients alive at some point after the diagnosis of their cancer.
- Lifetime risk is the probability of developing or dying from cancer, in the course of one’s lifespan.
- Median survival time (MST) is the period of time that has passed by which 50% of the affected individuals have died due to their disease.
- Absolute risk is the proportion of individuals affected usually expressed as a % or the number of individuals experiencing an event in relation to the population at risk.
- Relative risk (RR) is a comparison between two groups of individuals based on exposure to a risk factor to and is usually expressed as a ratio of the two proportions.
- Hazard ratio (HR)
- Confidence interval (CI)
Cancer was reported to have been diagnosed in 646 of 36,006 or 1.8% of live dogs in the 2004 KC survey of purebred dog health.
The relative risk (RR) for cancer in flatcoated retrievers was 2.1; meaning flatcoats were more than twice as likely to be diagnosed with cancer compared to all other pedigree dogs included in the survey. A total of 27% (4228/15,881) of dogs were reported to have died due to cancer from 1994 to 2003.