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Germline mutation rate predicts cancer mortality across 37 vertebrate species

Abstract Background and objectives Cancer develops across nearly every species. However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation. Cancer evolves in part throu...

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Published in:Evolution, medicine, and public health medicine, and public health, 2024, Vol.12 (1), p.122-128
Main Authors: Kapsetaki, Stefania E, Compton, Zachary T, Mellon, Walker, Vincze, Orsolya, Giraudeau, Mathieu, Harrison, Tara M, Abegglen, Lisa M, Boddy, Amy M, Maley, Carlo C, Schiffman, Joshua D
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container_end_page 128
container_issue 1
container_start_page 122
container_title Evolution, medicine, and public health
container_volume 12
creator Kapsetaki, Stefania E
Compton, Zachary T
Mellon, Walker
Vincze, Orsolya
Giraudeau, Mathieu
Harrison, Tara M
Abegglen, Lisa M
Boddy, Amy M
Maley, Carlo C
Schiffman, Joshua D
description Abstract Background and objectives Cancer develops across nearly every species. However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations, and therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species. Methodology We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species. Results Germline mutation rate was positively correlated with cancer mortality (P-value = 0.0008; R2 = 0.13). Controlling for species’ average parental age, maximum longevity, adult body mass or domestication did not improve the model fit (the change (Δ) in Akaike Information Criterion (AIC) was less than 2). However, this model fit was better than a model controlling for species trophic level (ΔAIC > 2). Conclusions and implications The increased death rate from cancer in animals with increased germline mutation rates may suggest underlying hereditary cancer predisposition syndromes similar to those diagnosed in human patients. Species with higher germline mutation rates may benefit from close monitoring for tumors due to increased genetic risk for cancer development. Early diagnoses of cancer in these species may increase their chances of overall survival, especially for threatened and endangered species. Lay Summary Cancer mortality rates vary across vertebrates. This study across 37 vertebrate species found a positive correlation between germline mutation rates and cancer mortality. The finding suggests some species may have hereditary cancer risks and could benefit from increased cancer screening.
doi_str_mv 10.1093/emph/eoae016
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However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations, and therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species. Methodology We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species. Results Germline mutation rate was positively correlated with cancer mortality (P-value = 0.0008; R2 = 0.13). Controlling for species’ average parental age, maximum longevity, adult body mass or domestication did not improve the model fit (the change (Δ) in Akaike Information Criterion (AIC) was less than 2). However, this model fit was better than a model controlling for species trophic level (ΔAIC &gt; 2). Conclusions and implications The increased death rate from cancer in animals with increased germline mutation rates may suggest underlying hereditary cancer predisposition syndromes similar to those diagnosed in human patients. Species with higher germline mutation rates may benefit from close monitoring for tumors due to increased genetic risk for cancer development. Early diagnoses of cancer in these species may increase their chances of overall survival, especially for threatened and endangered species. Lay Summary Cancer mortality rates vary across vertebrates. This study across 37 vertebrate species found a positive correlation between germline mutation rates and cancer mortality. 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However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations, and therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species. Methodology We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species. Results Germline mutation rate was positively correlated with cancer mortality (P-value = 0.0008; R2 = 0.13). Controlling for species’ average parental age, maximum longevity, adult body mass or domestication did not improve the model fit (the change (Δ) in Akaike Information Criterion (AIC) was less than 2). However, this model fit was better than a model controlling for species trophic level (ΔAIC &gt; 2). Conclusions and implications The increased death rate from cancer in animals with increased germline mutation rates may suggest underlying hereditary cancer predisposition syndromes similar to those diagnosed in human patients. Species with higher germline mutation rates may benefit from close monitoring for tumors due to increased genetic risk for cancer development. Early diagnoses of cancer in these species may increase their chances of overall survival, especially for threatened and endangered species. Lay Summary Cancer mortality rates vary across vertebrates. This study across 37 vertebrate species found a positive correlation between germline mutation rates and cancer mortality. 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title Germline mutation rate predicts cancer mortality across 37 vertebrate species
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