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A Multivariate Analysis of Life History Traits Across Species and Their Statistical Power to Predict Cancer Prevalence

Description

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…

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.

ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2021-05

Perception of Phase 1 Cancer Clinical Trials

Description

Mr. Green has stage 4 prostate cancer which has spread to the bones and liver and has become resistant to radiation and standard chemotherapy treatment. After 3 rounds of chemotherapy, his primary oncologist recommends that he participate in a clinical trial. He went to Dr. Red at the Saguaro Clinic…

Mr. Green has stage 4 prostate cancer which has spread to the bones and liver and has become resistant to radiation and standard chemotherapy treatment. After 3 rounds of chemotherapy, his primary oncologist recommends that he participate in a clinical trial. He went to Dr. Red at the Saguaro Clinic after reading on the internet about a new Phase 1 clinical trial that the clinic is hosting, which is designed to target a specific receptor called AB-111 that may be present in malignant prostate, cervical, ovarian, and breast cells. After signing consent and completing the blood screens in the morning at the clinic, Mr. Green is told his liver enzymes are too high and the ranges specified in the protocol prohibit him from enrolling. Mr. Green is noticeably affected and distressed at this news, and Dr. Red recommends end-of-life care. Behind the scenes, this event is noted on official medical documents and trial study rosters as a "screen fail." This narrative, while fictional, is realistic because similar events occur in cancer clinical trial sites on a regular basis. I look at the inner "world" and mental journey of possible clinical trial candidates as they seek out information about clinical trials and gain understanding of their function \u2014 specifically in the context of Phase 1 cancer clinical trials. To whom is the language of the term "screen failure" useful? How does excluding individuals from clinical trials protect their health and does the integrity of the trial data supersede the person's curative goals? What is the message that cancer patients (potential research subjects) receive regarding clinical trials from sources outside their oncologists?

ContributorsMcKane, Alexandra (Author) / Maienschein, Jane (Thesis director) / Ellison, Karin (Committee member) / Foy, Joseph (Committee member) / Barrett, The Honors College (Contributor)

Created2013-12

Monitoring the Molecular Quality of Biopsy Tissue Samples Using Volatile Organic Compounds

Description

A major challenge with tissue samples used for biopsies is the inability to monitor their molecular quality before diagnostic testing. When tissue is resected from a patient, the cells are removed from their blood supply and normal temperature-controlled environment, which causes significant biological stress. As a result, the molecular composition…

A major challenge with tissue samples used for biopsies is the inability to monitor their molecular quality before diagnostic testing. When tissue is resected from a patient, the cells are removed from their blood supply and normal temperature-controlled environment, which causes significant biological stress. As a result, the molecular composition and integrity undergo significant change. Currently, there is no method to track the effects of these artefactual stresses on the sample tissue to determine any deviations from the actual patient physiology. Without a way to track these changes, pathologists have to blindly trust that the tissue samples they are given are of high quality and fit for molecular analysis; physicians use the analysis to make diagnoses and treatment plans based on the assumption that the samples are valid. A possible way to track the quality of the tissue is by measuring volatile organic compounds (VOCs) released from the samples. VOCs are carbon-based chemicals with high vapor pressure at room temperature. There are over 1,800 known VOCs within humans and a number of these exist in every tissue sample. They are individualized and often indicative of a person’s metabolic condition. For this reason, VOCs are often used for diagnostic purposes. Their usefulness in diagnostics, reflectiveness of a person’s metabolic state, and accessibility lends them to being beneficial for tracking degradation. We hypothesize that there is a relationship between the change in concentration of the volatile organic compounds of a sample, and the molecular quality of a sample. This relationship is what would indicate the accuracy of the tissue quality used for a biopsy in relation to the tissue within the body.

ContributorsSharma, Nandini (Co-author) / Fragoso, Claudia (Co-author) / Grenier, Tyler (Co-author) / Hanson, Abigail (Co-author) / Compton, Carolyn (Thesis director) / Tao, Nongjian (Committee member) / Moakley, George (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)

Created2020-05

A survey of cancer prevalence within birds (the clave Aves).

Description

Cancer is a disease that occurs in many and perhaps all multicellular organisms. Current research is looking at how different life history characteristics among species could influence cancer rates. Because somatic maintenance is an important component of a species' life history, we hypothesize the same ecological forces shaping the life…

Cancer is a disease that occurs in many and perhaps all multicellular organisms. Current research is looking at how different life history characteristics among species could influence cancer rates. Because somatic maintenance is an important component of a species' life history, we hypothesize the same ecological forces shaping the life history of a species should also determine its cancer susceptibility. By looking at varying life histories, potential evolutionary trends could be used to explain differing cancer rates. Life history theory could be an important framework for understanding cancer vulnerabilities with different trade-offs between life history traits and cancer defenses. Birds have diverse life history strategies that could explain differences in cancer suppression. Peto's paradox is the observation that cancer rates do not typically increase with body size and longevity despite an increased number of cell divisions over the animal's lifetime that ought to be carcinogenic. Here we show how Peto’s paradox is negatively correlated for cancer within the clade, Aves. That is, larger, long-lived birds get more cancer than smaller, short-lived birds (p=0.0001; r2= 0.024). Sexual dimorphism in both plumage color and size differ among Aves species. We hypothesized that this could lead to a difference in cancer rates due to the amount of time and energy sexual dimorphism takes away from somatic maintenance. We tested for an association between a variety of life history traits and cancer, including reproductive potential, growth rate, incubation, mating systems, and sexual dimorphism in both color and size. We found male birds get less cancer than female birds (9.8% vs. 11.1%, p=0.0058).

ContributorsDolan, Jordyn Nicole (Author) / Maley, Carlo (Thesis director) / Harris, Valerie (Committee member) / Boddy, Amy (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)

Created2019-05

You Have the Power to Prevent Cancer

Description

With cancer rates increasing and affecting more people every year, I felt it was important to educate the younger generation about the potential factors that could put them at risk of receiving a cancer diagnosis later in life. I thought that this was important to do because most students, especially…

With cancer rates increasing and affecting more people every year, I felt it was important to educate the younger generation about the potential factors that could put them at risk of receiving a cancer diagnosis later in life. I thought that this was important to do because most students, especially in rural communities, are not taught the factors that increase your risk of getting cancer in the future. This leads to students not having the tools to think about the repercussions that their actions can have in their distant future in regard to their risk of getting cancer. I went to six schools throughout the valley and the White Mountains of Arizona with differing education levels and demographics to provide them with prevention strategies that they could implement into their daily lives to reduce their risk of getting cancer in the future. Some of the schools had curriculums that included cancer and some of the factors that increase your risk, while others never mention what is happening biologically when a person has cancer. I introduced factors such as no smoking or tobacco use, diet, exercise, sunscreen use, avoiding alcohol, and getting screened regularly. While at each school, I discussed the importance of creating these healthy habits while they are young because cancer is a disease that comes from the accumulation of mutations that can begin occurring in their bodies even now. After my presentation, 98.6% of the 305 students who viewed my presentation felt like they had learned something from the presentation and were almost all willing to implement at least one of the changes into their daily lives.

ContributorsGoforth, Michelle Nicole (Author) / Compton, Carolyn (Thesis director) / Lake, Douglas (Committee member) / Popova, Laura (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2020-05

Life History, Cancer Incidence, and Cancer Mortality in Non-Human Primates

Description

Cancer rates in our nearest relatives are largely unknown. Comparison of human cancer rates with other primates should help us to understand the nature of our susceptibilities to cancer. Data from deceased primates was gathered from 3 institutions, the Duke Lemur Center, San Diego Zoo, and Jungle Friends primate sanctuary.…

Cancer rates in our nearest relatives are largely unknown. Comparison of human cancer rates with other primates should help us to understand the nature of our susceptibilities to cancer. Data from deceased primates was gathered from 3 institutions, the Duke Lemur Center, San Diego Zoo, and Jungle Friends primate sanctuary. This data contained over 400 unique individuals across 45 species with information on cancer incidence and mortality. Cancer incidence ranged from 0-71% and cancer mortality ranged from 0-67%. We used weighted phylogenetic regressions to test for an association between life history variables (specifically body mass and lifespan) and cancer incidence as well as mortality. Cancer incidence did not correlate with both body mass and lifespan (p>.05) however, cancer mortality did (p<.05). However, it is uncertain if the variables can be used as reliable predictors of cancer, because the data come from different organizations. This analysis presents cancer incidence rates and cancer mortality rates in species where it was previously unknown, and in some primate species, is surprisingly high. Microcebus murinus(grey mouse lemur) appear to be particularly vulnerable to cancer, mostly lymphomas. Further studies will be required to determine the causes of these vulnerabilities.

ContributorsWalker, William Charles (Author) / Maley, Carlo (Thesis director) / Boddy, Amy (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2017-05

Trends in Tissue-Specific Cancers

Description

A big part of understanding cancer is understanding the cellular environment itthrives in by analyzing it from a microecological perspective. Humans and other species are affected by different cancer types, and this highlights the notion that there may be a correlation between specific tissues and neoplasia prevalence. Research shows that humans are the…

A big part of understanding cancer is understanding the cellular environment itthrives in by analyzing it from a microecological perspective. Humans and other species are affected by different cancer types, and this highlights the notion that there may be a correlation between specific tissues and neoplasia prevalence. Research shows that humans are the most susceptible to adenocarcinomas and carcinomas which include the following tissues: lungs, breast, prostate, and pancreas. Furthermore, research shows that adenocarcinoma accounts for 38.5% of all lung cancer cases, 20% of small cell carcinomas, and 2.9% of large cell carcinoma. The incidence of the most common cancer types in humans is consistently increasing annually. This study analyzes trends of tissue-specific cancers across species to examine possible contributors to vulnerability to cancer. I predicted that adenocarcinomas would be the most prevalent cancer type across the tree of life. To test this hypothesis, I reviewed over 130 species that reported equal to or greater than 50 individual necropsy pathology records across 4 classes (Mammalia, amphibia, Reptilia, Aves) and ranked them by neoplasia prevalence. This information was then organized in tables in descending order. The study’s resulting tables and data concluded that the hypothesis was correct. I found that across all species adenocarcinomas were the most common cancer type and account for 30.4% of malignancies reported among species. Future research should investigate how organ size contributes to neoplasia prevalence.

ContributorsPERAZA, ASHLEY (Author) / Maley, Carlo (Thesis advisor) / Boddy, Amy (Thesis advisor) / Baciu, Cristina (Committee member) / Arizona State University (Publisher)

Created2022

Reproductive Cancer Prevalence Across Mammalian Species

Description

Cancers of the reproductive tissues make up a significant portion of the cancer burden and mortality experienced by humans. Humans experience several proximal causative carcinogens that explain a portion of cancer risk, but an evolutionary viewpoint can provide a unique lens into the ultimate causes of reproductive cancer vulnerabilities. A…

Cancers of the reproductive tissues make up a significant portion of the cancer burden and mortality experienced by humans. Humans experience several proximal causative carcinogens that explain a portion of cancer risk, but an evolutionary viewpoint can provide a unique lens into the ultimate causes of reproductive cancer vulnerabilities. A life history framework allows us to make predictions on cancer prevalence based on a species’ tempo of reproduction. Moreover, certain variations in the susceptibility and prevalence of cancer may emerge due to evolutionary trade-offs between reproduction and somatic maintenance. For example, such trade-offs could involve the demand for rapid proliferation of cells in reproductive tissues that arises with reproductive events. In this study, I compiled reproductive cancer prevalence for 158 mammalian species and modeled the predictive power of 13 life history traits on the patterns of cancer prevalence we observed, such as Peto’s Paradox or slow-fast life history strategies. We predicted that fast-life history strategists will exhibit higher neoplasia prevalence risk due to reproductive trade-offs. Furthering this analytical framework can aid in predicting cancer rates and stratifying cancer risk across the tree of life.

ContributorsDarapu, Harshini (Author) / Maley, Carlo (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)

Created2022-05

Age as a Cancer Risk Factor Across Species

Description

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…

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.

ContributorsAksoy, Selin (Author) / Maley, Carlo (Thesis director) / Boddy, Amy (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)

Created2022-05

The Potential Utilization of Nutraceuticals as a Cancer Preventive Strategy

Description

Cancer is an ever-relevant disease with many genetic, social, environmental, and behavioral risk factors. One factor which has been garnering interest is the impact of nutrition on cancer. As a disease process, cancer is primarily driven by an accumulation of genetic aberrations. Recent epidemiological, pre-clinical, and clinical studies have demonstrated…

Cancer is an ever-relevant disease with many genetic, social, environmental, and behavioral risk factors. One factor which has been garnering interest is the impact of nutrition on cancer. As a disease process, cancer is primarily driven by an accumulation of genetic aberrations. Recent epidemiological, pre-clinical, and clinical studies have demonstrated various impacts of bioactive food molecules on the promotion or prevention of these oncogenic mutations. This work explores several of these molecules and their relation to cancer prevention and provides a sample meal plan, which highlights many additional molecules that are currently being studied.

ContributorsCurtin, Elise (Author) / Don, Rachael (Thesis director) / Compton, Carolyn (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)

Created2022-05

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