Bieuville Margaux, Dujon Antoine M, Raven Nynke, Ujvari Beata, Pujol Pascal, Eslami-S Zahra, Alix Panabières Catherine, Capp Jean-Pascal, Thomas Frédéric
CREEC (CREES), Unité Mixte de Recherches IRD 224-CNRS 5290-Université de Montpellier Montpellier France.
Institute of Organismic and Molecular Evolution (iomE) Johannes Gutenberg-Universität Mainz Germany.
Evol Appl. 2024 Oct 22;17(10):e70024. doi: 10.1111/eva.70024. eCollection 2024 Oct.
While it is recognised that most, if not all, multicellular organisms harbour neoplastic processes within their bodies, the timing of when these undesirable cell proliferations are most likely to occur and progress throughout the organism's lifetime remains only partially documented. Due to the different mechanisms implicated in tumourigenesis, it is highly unlikely that this probability remains constant at all times and stages of life. In this article, we summarise what is known about this variation, considering the roles of age, season and circadian rhythm. While most studies requiring that level of detail be done on humans, we also review available evidence in other animal species. For each of these timescales, we identify mechanisms or biological functions shaping the variation. When possible, we show that evolutionary processes likely played a role, either directly to regulate the cancer risk or indirectly through trade-offs. We find that neoplastic risk varies with age in a more complex way than predicted by early epidemiological models: rather than resulting from mutations alone, tumour development is dictated by tissue- and age-specific processes. Similarly, the seasonal cycle can be associated with risk variation in some species with life-history events such as sexual competition or mating being timed according to the season. Lastly, we show that the circadian cycle influences tumourigenesis in physiological, pathological and therapeutic contexts. We also highlight two biological functions at the core of these variations across our three timescales: immunity and metabolism. Finally, we show that our understanding of the entanglement between tumourigenic processes and biological cycles is constrained by the limited number of species for which we have extensive data. Improving our knowledge of the periods of vulnerability to the onset and/or progression of (malignant) tumours is a key issue that deserves further investigation, as it is key to successful cancer prevention strategies.
虽然人们认识到大多数（如果不是全部的话）多细胞生物体内都存在肿瘤形成过程，但这些不良细胞增殖最有可能在生物体整个生命周期中发生和发展的时间，目前仅有部分记录。由于肿瘤发生涉及不同机制，在生命的所有时期和阶段，这种可能性始终保持不变的可能性极小。在本文中，我们总结了关于这种变化的已知情况，考虑了年龄、季节和昼夜节律的作用。虽然大多数需要这种详细程度的研究是在人类身上进行的，但我们也回顾了其他动物物种的现有证据。对于这些时间尺度中的每一个，我们都确定了塑造这种变化的机制或生物学功能。在可能的情况下，我们表明进化过程可能发挥了作用，要么直接调节癌症风险，要么通过权衡间接发挥作用。我们发现肿瘤风险随年龄变化的方式比早期流行病学模型预测的更为复杂：肿瘤发展并非仅由突变导致，而是由组织和年龄特异性过程决定。同样，季节性周期可能与某些物种的风险变化相关，这些物种的生活史事件，如性竞争或交配，是根据季节安排的。最后，我们表明昼夜周期在生理、病理和治疗背景下都会影响肿瘤发生。我们还强调了在这三个时间尺度上这些变化核心的两种生物学功能：免疫和代谢。最后，我们表明，我们对肿瘤发生过程与生物周期之间纠缠的理解受到我们拥有广泛数据的物种数量有限的限制。提高我们对（恶性）肿瘤发生和/或进展的易患期的认识是一个关键问题，值得进一步研究，因为这是成功的癌症预防策略的关键。
