迈向更稳健的比较肿瘤学:对佩托悖论的贝叶斯再分析及脊椎动物比较癌症风险研究的探讨
Towards a more robust comparative oncology: a Bayesian reanalysis of Peto's paradox and discussion of comparative cancer risk studies in vertebrates.
作者信息
Dujon Antoine M, Biro Peter A, Ujvari Beata, Thomas Frédéric
机构信息
School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria 3216, Australia.
CREEC/(CREES), MIVEGEC, Unité Mixte de Recherches, IRD 224-CNRS 5290, Université de Montpellier, Montpellier, France.
出版信息
R Soc Open Sci. 2025 Jul 9;12(7):250840. doi: 10.1098/rsos.250840. eCollection 2025 Jul.
The multistage carcinogenesis model predicts that cancer risk should increase with body size and longevity owing to greater cell numbers and divisions, which provide more opportunities for mutations. However, the perceived lack of such associations across species, named 'Peto's paradox', suggests that larger or longer-lived animals may have evolved enhanced cancer suppression mechanisms. Empirical tests of this paradox have been limited by data availability, but large-scale zoo datasets now enable comparative analyses of cancer prevalence in vertebrates. Currently used statistical methods, however, often fail to adequately account for uncertainty in key model parameters. In this study, we use Bayesian methods to reanalyse these datasets and explore Peto's paradox, emphasizing the importance of quantifying uncertainty in comparative oncology. Our results show that body mass is positively associated with malignancy risk in mammals and amphibians, while it is negatively associated with cancer mortality in mammals. Longevity is positively associated with malignancy risk in non-avian sauropsids and amphibians. However, these relationships are accompanied by effect sizes with substantial uncertainty, primarily owing to small sample sizes. Through simulations, we demonstrate the limitations of current datasets and models. We also discuss the broader implications of Peto's paradox and suggest recommendations for improving future research on cancer risk across species.
多阶段致癌模型预测,由于细胞数量更多和分裂次数更多,癌症风险应会随着体型和寿命的增加而上升,因为这会提供更多的突变机会。然而,在物种间所察觉到的这种关联缺失,即所谓的“皮托悖论”,表明体型较大或寿命较长的动物可能已经进化出了增强的癌症抑制机制。对这一悖论的实证检验一直受到数据可用性的限制,但现在大规模的动物园数据集能够对脊椎动物的癌症患病率进行比较分析。然而,目前使用的统计方法往往未能充分考虑关键模型参数中的不确定性。在本研究中,我们使用贝叶斯方法重新分析这些数据集并探究皮托悖论,强调在比较肿瘤学中量化不确定性的重要性。我们的结果表明,体重与哺乳动物和两栖动物的恶性肿瘤风险呈正相关,而与哺乳动物的癌症死亡率呈负相关。寿命与非鸟类蜥形纲动物和两栖动物的恶性肿瘤风险呈正相关。然而,这些关系伴随着效应大小存在大量不确定性,主要是由于样本量较小。通过模拟,我们展示了当前数据集和模型的局限性。我们还讨论了皮托悖论的更广泛影响,并为改进未来跨物种癌症风险研究提出建议。
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