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After receiving a diagnosis of cancer, I have often observed patients grappling with the questions; “What caused it?”, and “Could I have prevented this?”.
As an oncology registrar facing these queries in the clinic, I would often attempt to reassure them that it is just “one of those things”, and that they should not seek to blame themselves, but these fundamental questions are difficult to answer on an individual basis.
Most difficult to explain is the young child who develops cancer without any apparent genetic trigger, and who hasn’t even lived long enough for environmental or lifestyle choices to impact upon them.
It is difficult to convey the message that the risk of developing cancer is dependent on probabilities. There is a paradox when considering the case of the lifelong heavy smoker who lives into old age without any ill effects, compared to the patient diagnosed with cancer after living a blameless life.
The causes of cancer
For some tumour types, there are well characterised risk factors which are modifiable by an individual. It is estimated that approximately 42% of all cancers are preventable.
There is widespread public knowledge regarding the effects of smoking, alcohol, obesity and exposure to ultraviolet light on the risk of certain cancers. Smoking is an excellent example of a lifestyle habit linked to cancer; approximately 90% of lung cancers are preventable by avoiding smoking.
Some cancers have clear associations with viruses, such as that of cancer of the cervix and Human Papilloma Virus (HPV), and vaccination programs have led to significant reductions in incidence.
It is estimated that as little as 5%-10% of cancers arise due to heritable genetic mutations.
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The "bad luck" hypothesis
Many of you will be familiar with the headlines in the press such as “Most cancers caused by bad luck”, and the controversy that followed.
It was prompted by a study published in Science in 2015 by Tomasetti and Vogelstein suggesting that for any individual, two thirds of the variation in cancer risk is due to mutations occurring randomly at the time of DNA replication, i.e. the “bad luck” hypothesis.
Therefore, they postulated that only a third of the total risk can be explained by environmental exposures or inherited genetic predispositions. They discovered that risk is proportional to the number of stem cell divisions taking place within different organs during a person’s lifetime, thus accounting for the higher incidence of cancers in the bowel, skin, and lung compared to tissues with lower cell divisions such as the brain.
This theory concurs with the fact that the risk of developing cancer increases with age, as the more cell divisions that have taken place the greater the chance that DNA is imperfectly replicated.
The truth: a complex interplay
A Nature publication in 2016 by Song Wu’s team of Stony Brook University, New York, challenged the “bad luck” hypothesis, and concluded that the causes of cancer reflect a complex interplay between intrinsic (random mutations) and extrinsic (environmental) factors.
It must be remembered that for a tumour to arise, a succession of mutations will have taken place, some of which may be due to an environmental trigger. Also, different cancers are acquired differently.
In some cancer types, most of the mutations found within the tumour are randomly acquired, and in others the converse is true. Certain cancers have definite environmental influences (yet to be identified), as illustrated by geographical variation in incidence (for example in prostate and breast cancers).
If an individual were to move from living an area of low to high risk, they adopt the levels of risk in their new home country. So, the picture is not clear cut, and the conventional understanding that cancer development is multifactorial still stands.
Avoiding a fatalistic attitude
The downsides of the “bad luck” hypothesis are that patients may adopt a fatalistic attitude regarding modification of lifestyle factors. There has always been an emphasis on cancer prevention in public health campaigns, as well as increasing public awareness of the early warning signs and symptoms of cancer.
Whilst the “bad luck” hypothesis may give comfort to some by removing blame from patients, the downsides are that patients may adopt a fatalistic attitude regarding modification of lifestyle factors.
We should empower patients to lead healthier lives, not only for the benefits of cancer risk reduction, but numerous other illnesses such as ischaemic heart disease and diabetes.
With pressure on healthcare funding mounting, we should accept a collective responsibility to eat more healthily, be more active, and limit our exposure to known cancer causing agents.
Research has now moved on
Research is now leading away from the basis that mutated genes form the entire basis for a cancer’s development; much more is now understood about the role of the surrounding cells (stroma), markers of inflammation, and the immune system.
It is clear that many questions remain about the causes of many cancers, and it is crucial that the scientific community continue in their quest to answer these.
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