Data from: Importance of metabolic rate to the relationship between the number of genes in a functional category and body size in Peto's paradox for cancer

Elucidation of tumour suppression mechanisms is a major challenge in cancer biology. Therefore, Peto's paradox, or low cancer incidence in large animals, has attracted focus. According to the gene-abundance hypothesis, which considers the increase/decrease in cancer-related genes with body size, researchers evaluated the associations between gene abundance and body size. However, previous studies only focused on a few specific gene functions and have ignored the alternative hypothesis (metabolic rate hypothesis): in this hypothesis, the cellular metabolic rate and subsequent oxidative stress decreases with increasing body size. In this study, we have elected to explore the gene-abundance hypothesis taking into account the metabolic rate hypothesis. Thus, we comprehensively investigated the correlation between the number of genes in various functional categories and body size while at the same time correcting for the mass-specific metabolic rate (Bc). A number of gene functions that correlated with body size were initially identified, but they were found to be artefactual due to the decrease in Bc with increasing body size. By contrast, immune system-related genes were found to increase with increasing body size when the correlation included this correction for Bc. These findings support the gene-abundance hypothesis and emphasize the importance of also taking into account the metabolic rate when evaluating gene abundance–body size relationships. This finding may be useful for understanding cancer evolution and tumour suppression mechanisms as well as for determining cancer-related genes and functions.阐明肿瘤抑制机制是癌症生物学领域的核心挑战之一。因此，佩托悖论（Peto's Paradox）——即大型动物癌症发病率较低——引发了学界广泛关注。基因丰度假说（gene-abundance hypothesis）认为癌症相关基因的数量会随体型大小发生增减变化，此前研究者基于该假说评估了基因丰度与体型大小之间的关联。然而，既往研究仅聚焦于少数特定的基因功能类别，且忽略了另一替代假说——代谢速率假说（metabolic rate hypothesis）：该假说提出，细胞代谢速率及随之产生的氧化应激水平会随体型增大而降低。本研究兼顾代谢速率假说对基因丰度假说展开探究，系统分析了不同功能类别基因的数量与体型大小之间的相关性，并同时对单位质量代谢率（Bc）进行校正。研究初期曾发现多个与体型大小存在相关性的基因功能类别，但后续证实这些关联实为假象，其源于Bc随体型增大而降低这一混杂因素。与之相对，在校正Bc后，免疫系统相关基因的数量随体型增大呈现显著上升趋势。本研究结果验证了基因丰度假说，同时强调在分析基因丰度与体型大小的关联时，需同时考虑代谢速率因素的重要性。该发现可为理解癌症演化与肿瘤抑制机制、鉴定癌症相关基因及功能提供理论参考。