We Asked the Experts: Providing the Road Map to Uncovering the Pathophysiology of Young-Onset Cancer to Guide Treatment
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EDITORIAL PERSPECTIVE
We Asked the Experts: Providing the Road Map to Uncovering the Pathophysiology of Young-Onset Cancer to Guide Treatment and Preventive Strategies Savio George Barreto1,2
Ó Socie´te´ Internationale de Chirurgie 2020
Until recently, the jury was still out on whether ‘youngonset’ cancer, defined as cancer occurring in individuals under the age of 40 years, was a distinct entity with outcomes worse off than sporadic cancers that generally occur in older individuals [1]. In the last 5 years, there have been numerous publications highlighting a rise in the incidence of young-onset cancers affecting the ovary, breast, rectum, and pancreas. Interestingly, the aetiology of these cancers cannot be traced back to pre-existing familial cancer syndromes [2, 3]. We are, thus, clearly beyond the stage of debating the existence of the entity. It is time to set the agenda for our approach to deciphering its pathophysiology to enable us develop strategies for early detection, appropriate treatment, and the identification of opportunities, if any, to prevent these cancers. Thus far, the risk factors linked to the development of young-onset cancers appear similar to those involved in sporadic cancers, namely alcohol, smoking, and obesity. However, does our current understanding of carcinogenesis allow us to accept these findings at face value, or are we regressing to a ‘one-size-fits-all’ approach in oncology? A recent publication by Lahouel et al. [4] presented for the first time a data-driven, mathematical model of the process of tumour evolution taking into consideration the fitness advantages for driver genes and carrying capacity [4]. The authors used their vast experience over decades of cancer research to prepare the model that accounts for the three & Savio George Barreto [email protected]; [email protected] 1
Division of Surgery and Perioperative Medicine, Department of Surgery, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia
2
College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
mechanisms that confer fitness advantage, namely cell fate, cell survival, and genome maintenance, and total number of clonal somatic mutations accumulated in a cell lineage. What is striking in this manuscript is the discovery of the timing of driver gene mutations. The authors noted the first hit to occur at a median age of 14.4 years for colon cancer and 14.6 years for pancreatic cancer, with the full development of malignancy taking on average another 50 years. In young-onset cancers, we can postulate an acceleration of events in terms of the timing of both first and second ‘hits’. It is difficult to accept that an individual would be exposed to the proposed risk factors within the first couple of decades of life in a magnitude to an extent that would induce mutations and cancer by the age of 40 years. I hypothesize that what is more likely to play a role in carcinogenesis in young-onset cancers is an ‘in utero’ insult to the foetus that speeds up, or lead
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