Review
Version 1
Preserved in Portico This version is not peer-reviewed
From Churchill to Elephants: The Role of Protective Genes Against Cancer
Version 1
: Received: 25 December 2023 / Approved: 26 December 2023 / Online: 28 December 2023 (02:40:55 CET)
A peer-reviewed article of this Preprint also exists.
Gazzellone, A.; Sangiorgi, E. From Churchill to Elephants: The Role of Protective Genes against Cancer. Genes 2024, 15, 118. Gazzellone, A.; Sangiorgi, E. From Churchill to Elephants: The Role of Protective Genes against Cancer. Genes 2024, 15, 118.
Abstract
Richard Peto’s Paradox, first described in 1975 from an epidemiological perspective, established an inverse correlation between the probability of developing cancer in multicellular organisms and the number of cells. Larger animals exhibit fewer tumors compared to smaller ones, though exceptions exist. Mice are more susceptible to cancer than humans, while elephants and whales demonstrate significantly lower cancer prevalence rates than humans. How nature and evolution have addressed the issue of cancer in the animal kingdom remains largely unexplored.
In the field of medicine, much attention has been devoted to cancer predisposing genes, as they offer avenues for intervention, including blocking, downregulating, early diagnosis, and targeted treatment. Predisposing genes also tend to manifest clinically earlier and more aggressively, making them easier to identify. However, despite significant strides in modern medicine, the role of protective genes lags behind.
Identifying genes with a mild predisposing effect poses a significant challenge. Consequently, comprehending the protective function conferred by genes becomes even more elusive, and their very existence is subject to questioning. While the role of variable expressivity and penetrance defects of the same variant in a family is well-documented for many hereditary cancer syndromes, attempts to delineate the function of protective/modifier alleles have been restricted to a few instances.
In this review, we endeavor to elucidate the role of protective genes observed in the animal kingdom and within certain genetic syndromes that appear to act as cancer-resistant/repressor alleles. The ultimate goal is to discern why individuals, like Winston Churchill, managed to live up to 91 years of age, despite engaging in minimal physical activity, consuming large quantities of alcohol daily, and not abstaining from smoking.
Keywords
cancer protective genes; Down syndrome; Laron syndrome
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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