Life is like a box of chocolates – but do we know what we’re gonna get?

This is the Second Prize Winner of the 2024 Molecular Oncology Writing Competition: Impact of the exposome on cancer risk.
Life is like a box of chocolates – but do we know what we’re gonna get?
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As part of World Cancer Day (4th Feb), the journal of Molecular Oncology invited researchers to take part in a writing competition aimed at highlighting the impact of the exposome on cancer risk. This entry, by Emily Southworth (University of Edinburgh, UK), received the second prize.

Can you recall how many hours you’ve spent in standstill traffic? How many times have you been sunburnt, how many units of alcohol have you ever consumed? What about red meat; how much, to the kilogram, have you eaten in your life? Tell me the number of times you’ve ever felt stressed, and how much cortisol you produced?! Although these questions get more ridiculous, and impossible to answer, they represent a handful of factors that contribute to the concept known as the ‘exposome’. First coined in 2005, the exposome (‘expo’ = exposure, ‘ome’ = wholeness or completeness) describes the accumulation of external and internal factors we are each individually exposed to, from our time in the womb until our death [1]. The study of the exposome aims to monitor and even predict our propensity to diseases and – despite what I’ve just asked – is an actionable and fruitful area of epidemiological research.

Our DNA, the genetic sequence found in every 30 or so trillion cells in our body, is famously coined as our ‘biological building blocks’ – everything we can do we owe to this complex molecular structure. That being said, this also means when we become unwell, defects (or ‘mutations’) in our DNA are often the culprit. Taking cancer as an example, how exactly does DNA acquire enough mutations to initiate disease, through our environment? One of the most famous examples of an external factor leading to increased cancer risk is cancer incidence in smokers of tobacco, versus non-smokers. Cigarette smoke contains 70 chemicals which are directly linked to 15 types of cancer[2]. These chemicals latch onto our DNA and activate our immune system, resulting in inflammation and an abundance of alterations to DNA composition. The building blocks needed to initiate the repair of DNA become incorrectly written; other blocks become inaccessible. Our cells, once efficient at correcting mistakes in the genetic code, are no longer as keen-eyed. More and more mutations accumulate that allow pre-cancerous cells to expand in number; cells evade the immune system; cells resist pathways instructing them to die. Over time, this biological response is strong enough to produce a mass of cells – a malignant tumour, or cancer.  But not everyone who has ever smoked gets cancer. The most obvious explanation is that the relative risk of cancer is proportional to both time spent smoking, as well as the number of cigarettes smoked within this time. The more cigarette smoke – the more chemicals our cells are exposed to – the more chance our DNA becomes damaged. Duration and intensity of tobacco smoking – a measurable factor within the exposome.

That being said, people who have smoked for the same duration and intensity are also at variable risk of cancer – why? A question often asked in research of the exposome is the interplay between different exposures, meaning how one factor may lessen or strengthen the impact another factor has on cancer predisposition. Many study participants who report as current smokers and adhere to a Mediterranean-like diet are at lower cancer risk than those who don’t report the same dietary habits but still smoke[3, 4]. Regular consumption of foods such as beans, nuts, olive oil is associated with a lower dietary inflammatory index (DII) [5], an algorithm developed through measuring blood concentrations of biomarkers produced in response to inflammation. Tobacco smoking is undoubtedly bad for your health; however, our diet may reduce the inflammatory burden faced by our cells, thus meaning our DNA may not take quite as many hits. Taking this even further, people who have smoked a similar number of cigarettes, for a similar duration of time, and have eaten relatively the same diet don’t all get cancer. Those that do may get very different cancer types. Who of these people live in polluted cities? Who has been exposed to the most UV? The diversity and quantity of exposures we are each exposed to makes our exposome unique; in collaboration with your own genetic code, also unique, individual cancer risk can vary greatly.

While it is clear our health is influenced by the environment we live in, what about the exposures that we cannot change in our day to day lives? Climate change has meant, for some of us, severe wildfires; flooding; food insecurity[6]. Some of us live close by to or within warzones. Can someone living in a region where vegetable crops have been destroyed make the same dietary choices as someone elsewhere? Is it harder for someone facing the loss of their home and livelihood to not pick up a cigarette or find time to exercise, than someone who isn’t? The exposome is one reason of many why it is more important than ever to consider not just our own quality of life, but that of others, in the global fight against cancer.

References

  1. Wild, C.P., Complementing the Genome with an “Exposome”: The Outstanding Challenge of Environmental Exposure Measurement in Molecular Epidemiology. Cancer Epidemiol Biomarkers Prev, 2005. 14(8): p. 1847-1850.
  2. Cancer Research UK. What's in a cigarette? ; Available from: https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/smoking-and-cancer/whats-in-a-cigarette-0.
  3. Couto, E., et al., Mediterranean dietary pattern and cancer risk in the EPIC cohort. Br J Cancer, 2011. 104(9): p. 1493-1499.
  4. Schulpen, M. and P.A. van den Brandt, Adherence to the Mediterranean Diet and Overall Cancer Incidence: The Netherlands Cohort Study. J Acad Nutr Diet, 2021. 121(2): p. 242-252.
  5. Salas-Salvadó, J. and C. Papandreou, Chapter 1 - The Mediterranean diet: History, concepts and elements, in The Mediterranean Diet (Second Edition), V.R. Preedy and R.R. Watson, Editors. 2020, Academic Press. p. 3-11.
  6. United Nations. What Is Climate Change? February 2024]; Available from: https://www.un.org/en/climatechange/what-is-climate-change.

Photo by Thomas Stephan on Unsplash

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