The following post is written by Dr Colin Lindsay, MBChB PhD. Clinical Senior Lecturer and Honorary Consultant in Medical Oncology at The Christie NHS Foundation Trust and Division of Molecular & Clinical Cancer Sciences, University of Manchester.
There are only a few questions I am frequently asked by patients and probably the most obvious to ask is: “do you know what caused the cancer?” Although the answer depends on the type of cancer being discussed, I often have to reply by saying “no – I don’t”, wishing I had more to offer.
I’ll then go on to explain, as sensitively as possible, that the reasons for this are a) most cancers are not caused by known environmental factors, such as ultraviolet light for skin cancer or smoking for lung cancer, and b) only a minority of cases are a result of cancer-causing genes that have been inherited or ‘passed on’ by other family members. All other cancers – the majority – are caused by a build-up of mutational processes resulting from internal and unknown environmental insults. These occur throughout life and cause tumours to grow at different points depending on when different combinations of these genetic alterations coincide.
I am therefore left to tell most patients that they have been “unlucky” and there is little they could have done to prevent their diagnosis, at least based on our current knowledge.
All other cancers – the majority – are caused by a build-up of mutational processes resulting from internal and unknown environmental insults
How genomes can lead to learning more about environmental carcinogens
I am writing in this blog because our knowledge of cancer causes is beginning to change, and the main breakthrough has come from our vastly improved capability to examine cancer genetics (the cancer ‘genome’) in a timely and cost-efficient way over the past 10 years. In 2000, the first human genome was described following decades of research and planning, but nowadays processing or ‘sequencing’ of a genome is much simpler, taking ~1 hour and costing approximately £1000.
Our hope is that an improved knowledge of the cancer genome will allow us to better identify and characterise environmental carcinogens. For instance, with the advent of largescale genetic work, the Wellcome Sanger Institute near Cambridge has developed a genetic classification for cancer that leads us towards its root causes and allows us to consider future strategies for cancer prevention. This genetic work has now been rolled out across Manchester for a small number of cancers as part of the Genomics England 100,000 genome project, and I have been lucky enough to help lead a small team examining this new classification.
Our hope is that an improved knowledge of the cancer genome will allow us to better identify and characterise environmental carcinogens
So far, over 45 different ‘signatures’ of genetic attack have been described which can stimulate the changes that lead to cancer. Probably a good way to visualise what these signatures are is if you consider what happens when you log in to the internet: in the same way that any computer time will leave an indelible and traceable record on your desktop or mobile phone, the same principle is transferrable to any environmental or internal genetic insult attacking the cancer genome. Of particular interest is that, although some signatures are attributable to known causes (eg. smoking and UV light), much of the potential in this work is that the causes of many signatures have yet to be identified. So we know they exist in the cancer genome and we think that they are contributing to cancer, but we’re yet to establish what’s causing the genetic signatures or ‘imprints’ we see in many cases.
Lung cancer and pollution
The lung cancer landscape is particularly interesting and, of course, relevant to the environment we live in since the lungs are the first organ that encounters the air we breathe. Yes, there is a heavy smoking contribution in many cases — but this is by no means the only contribution, and there are also 20% of lung cancers which have no smoking contribution at all. Our strong belief is therefore:
- The role of pollution and environmental carcinogens in cancer will be characterized and reinforced by this work.
- Defining this problem through research into cancer genetics will facilitate green energy and public health cancer prevention strategies.
20% of lung cancers … have no smoking contribution at all
At present, the vast majority of cancer genetic research is influenced by drug companies hoping to justify their products for treatment when a cancer becomes incurable. What we are trying to do is shift this approach so that genetics can be applied to its full potential, informing cancer causes and eventual prevention.
How do we move forward?
It is not all plain sailing from here. The challenge we have moved on to is interpreting an enormous amount of genetic changes we see from sequencing of every cancer. To give you an idea of the scale of these data, a full set of genetic results from just two cancers is enough to occupy the memory of a standard laptop. Adding to this complexity, most of these changes will be part of normal variation and irrelevant to the cancer that is being assessed, so we still need to devise new ways and systems of picking out those rare genetic alterations that are genuinely causing harm by promoting tumours.
I hope I have demonstrated that transitioning to a clean energy system may not just be important for the protection of our environment, it will very likely be hugely important for the protection of our health. Although you might not always be aware of it, we are working in the background on these fundamental and important long-term questions for the health of you and your family.
For more information about the work discussed in this article, contact Jane Rogan at the Manchester Cancer Research Centre Biobank: firstname.lastname@example.org