Compton Zachary T, Mellon Walker, Harris Valerie K, Rupp Shawn, Mallo Diego, Kapsetaki Stefania E, Wilmot Mallory, Kennington Ryan, Noble Kathleen, Baciu Cristina, Ramirez Lucia N, Peraza Ashley, Martins Brian, Sudhakar Sushil, Aksoy Selin, Furukawa Gabriela, Vincze Orsolya, Giraudeau Mathieu, Duke Elizabeth G, Spiro Simon, Flach Edmund, Davidson Hannah, Li Christopher I, Zehnder Ashley, Graham Trevor A, Troan Brigid V, Harrison Tara M, Tollis Marc, Schiffman Joshua D, Aktipis C Athena, Abegglen Lisa M, Maley Carlo C, Boddy Amy M
Arizona Cancer Evolution Center, The Biodesign Institute, Arizona State University, Tempe, Arizona.
University of Arizona Cancer Center, Tucson, Arizona.
Cancer Discov. 2025 Jan 13;15(1):227-244. doi: 10.1158/2159-8290.CD-24-0573.
Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto's paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes. See related commentary by Metzger, p. 14.
癌症在多细胞物种中普遍存在,但如何解释不同物种间癌症患病率的差异呢?利用涵盖四足动物三个分支(两栖动物、蜥形纲动物和哺乳动物)的292个物种的16049份尸检记录,我们发现肿瘤形成和恶性肿瘤患病率随成年个体体重增加(与佩托悖论相反)以及体细胞突变率上升而增加,但随妊娠期延长而降低。只有在我们控制妊娠期后,成年个体体重与恶性肿瘤患病率之间的关系才明显显现。癌症易感性的进化似乎经历了突然转变,随后是稳定选择。肿瘤形成患病率的异常值包括普通鼠海豚(<1.3%)、罗德里格斯果蝠(<1.6%)、黑脚企鹅(<0.4%)、雪貂(63%)和负鼠(35%)。弄清楚为什么有些物种的癌症水平特别高或特别低,可能有助于更好地理解癌症综合征以及管理和预防癌症的新策略。意义:进化已经在多种物种中发现了抑制癌症的机制。通过分析兽医尸检记录,我们可以识别出癌症患病率异常高或低的物种。发现癌症易感性和抗性的机制可能有助于改进癌症预防并解释癌症综合征。见梅茨格的相关评论,第14页。