Cancer is a disease acquired through mutations which leads to uncontrolled cell division and destruction of normal tissue within the body. Recent increases in available cross-species data of cancer in mammals, reptiles, birds, and other vertebrates has revealed that the prevalence of cancers varies widely across species. Life-history theory suggests that there could be traits that potentially explain some of that variation. We are particularly interested in species that get very little cancer. How are they preventing cancer and can we learn from them how to prevent cancer in humans? Comparative oncology focuses on the analysis of cancer prevalence and traits in different non-human species and allows researchers to apply their findings to humans with the goal of improving and advancing cancer treatment. We incorporate the predictions that animals with larger bodies have evolved better cancer suppression mechanisms than animals with small bodies. Ruminants in the past were larger in size than modern day ruminants and they may have retained cancer defenses from their large ancestors. The strong cancer defenses and small body size combined may explain the low prevalence of cancer in Ruminants. This paper aims to evaluate the presence of benign and malignant neoplasia prevalence across multiple ruminant species following a time of dramatic decrease in body size across the clade. Our aim is to illuminate the potential impact that these shifts in body size had on their cancer prevalence as well as test the statistical power of other key life history variables to predict cancer prevalence.
Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.
Background
In 2015, the Zika arbovirus (ZIKV) began circulating in the Americas, rapidly expanding its global geographic range in explosive outbreaks. Unusual among mosquito-borne diseases, ZIKV has been shown to also be sexually transmitted, although sustained autochthonous transmission due to sexual transmission alone has not been observed, indicating the reproduction number (R0) for sexual transmission alone is less than 1. Critical to the assessment of outbreak risk, estimation of the potential attack rates, and assessment of control measures, are estimates of the basic reproduction number, R0.
Methods
We estimated the R0 of the 2015 ZIKV outbreak in Barranquilla, Colombia, through an analysis of the exponential rise in clinically identified ZIKV cases (n = 359 to the end of November, 2015).
Findings
The rate of exponential rise in cases was ρ = 0.076 days[superscript −1], with 95% CI [0.066,0.087] days[superscript −1]. We used a vector-borne disease model with additional direct transmission to estimate the R0; assuming the R0 of sexual transmission alone is less than 1, we estimated the total R0 = 3.8 [2.4,5.6], and that the fraction of cases due to sexual transmission was 0.23 [0.01,0.47] with 95% confidence.
Interpretation
This is among the first estimates of R0 for a ZIKV outbreak in the Americas, and also among the first quantifications of the relative impact of sexual transmission.
Human societies are unique in the level of cooperation among non-kin. Evolutionary models explaining this behavior typically assume pure strategies of cooperation and defection. Behavioral experiments, however, demonstrate that humans are typically conditional co-operators who have other-regarding preferences. Building on existing models on the evolution of cooperation and costly punishment, we use a utilitarian formulation of agent decision making to explore conditions that support the emergence of cooperative behavior. Our results indicate that cooperation levels are significantly lower for larger groups in contrast to the original pure strategy model. Here, defection behavior not only diminishes the public good, but also affects the expectations of group members leading conditional co-operators to change their strategies. Hence defection has a more damaging effect when decisions are based on expectations and not only pure strategies.
Age is the most significant risk factor for cancer development in humans. The somatic mutation theory postulates that the accumulation of genomic mutations over time results in cellular function degradation which plays an important role in understanding aging and cancer development. Specifically, degradation of the mechanisms that underlie somatic maintenance can occur due to decreased immune cell function and genomic responses to DNA damage. Research has shown that this degradation can lead to the accumulation of mutations that can cause cancer in humans. Despite recent advances in our understanding of cancer in non-human species, how this risk factor translates across species is poorly characterized. Here, we analyze a veterinarian cancer dataset of 4,178 animals to investigate if age related cancer prevalence is similar in non-human animals. We intend for this work to be used as a primary step towards understanding the potential overlap and/or uniqueness between human and non-human cancer risk factors. This study can be used to better understand cancer development and how evolutionary processes have shaped somatic maintenance across species.