Examining the association between genomic ancestry and hepatoblastoma risk
My experience as a research intern at the University of Minnesota, Department of Pediatrics
by Nicole Branch
Background:
Hepatoblastoma has the fastest-rising incidence of any childhood cancer and is the most common childhood liver cancer (Hubbard et al). Still, hepatic tumors make up a very small portion of all childhood cancers globally and a lot is unknown about the causes of hepatoblastoma due to its rarity, although previous studies have linked it to low birth weight and some inherited syndromes (Spector & Birch). In addition, incidence of the cancer was found to be lower in self-identified Black individuals compared to White individuals and higher in self-identified Hispanic individuals compared to White individuals (Marcotte et al). Self-identified race and ethicity are social factors that can have an impact on health outcomes, but the study I took part in last summer looked to understand the genomic influence on hepatoblastoma risk based on these trends in incidence for self-identified ethnicity, specifically exploring whether Amerindian* ancestry has any association with risk for hepatoblastoma.
*The term my lab used to refer to individuals indigenous to the Americas
Organization's Work
I worked in the Division of Epidemiology and Clinical Research in the Department of Pediatrics at the University of Minnesota, where they work to improve children’s health through research in the etiology, prevention, treatment, and outcomes of childhood diseases. The group I worked in specifically has goals of improving outcomes for children diagnosed with cancer and blood diseases. The division comprises individuals with training and expertise in epidemiology, genetics, molecular biology, pediatric obesity medicine, pharmacology, biostatistics, pediatrics, and methodology (University of Minnesota).
My Role
Over the course of the summer, I worked on a hybrid schedule where I went into the office a couple times a week. I had the opportunity to participate in journal club and lab meetings alongside the time I spent working on my research project, and I presented my findings to the department at the end of my research experience. Before beginning to work on my analysis, I spent time doing background research into hepatoblastoma and reading about other similar studies to understand the context behind the data I was given.
Under the guidance of Dr. Erin Marcotte, I conducted an analysis of genomic ancestry data and its connection to hepatoblastoma risk (see the photo on the right for how the data was obtained). Initially, I investigated the relationship between self-identified race/ethnicity and genomic ancestry to narrow down which ancestry proportions to focus on based on the previously identified increased risk of hepatoblastoma in self-identified Hispanic individuals. Our analysis revealed that Hispanic individuals had higher Amerindian ancestry on average (see bar chart below), indicating a possible link between increased hepatoblastoma risk and higher Amerindian ancestry proportions. We then categorized the ancestry percentage into "high" (≥10% Amerindian ancestry) and "low" (<10% Amerindian ancestry) groups. Our results showed that the odds of having hepatoblastoma were 1.72 times greater for individuals with high Amerindian ancestry compared to those with low Amerindian ancestry. We also found that after controlling for sex, birth weight, and mother's education level, the odds of having hepatoblastoma for an individual with high Amerindian ancestry were 1.76 times greater than for those with low Amerindian ancestry. While this analysis did identify an association, further research is required to explore genomic evidence that could account for the increased risk of hepatoblastoma among individuals with higher Amerindian ancestry.
Plot representing the relationship between genomic ancestry proportions and Hispanic ancestry for individuals in our data
Lengend: SAS = South Asian, EUR = European, EAS = East Asian, AMR = Amerindian, AFR = African
Lessons Learned
During this summer internship, I gained valuable exposure to epidemiological research methods and acquired new skills in data wrangling, analysis, and visualization techniques in the statistical software R. Additionally, I gained experience in communicating my research effectively, both in written and verbal formats, to audiences familiar with the subject matter and those without prior knowledge of childhood cancer, and I experienced the challenges of researching rare diseases. As the project I worked on utilized both self-identified race/ethnicity and genomic ancestry to measure cancer risk, I also spent some time researching the history of admixture between populations throughout the world and the importance of being cautious with the language used when discussing race and ancestry in a research setting. It is crucial to differentiate between race/ethnicity and ancestry when presenting results like these because both can impact health differently. Self identified race and ethnicity affect how society views and treats individuals and are social determinants that influence an individual’s ability to be healthy, while ancestry is more connected to genomic factors that influence health. Using the two as interchangeable terms can lead to inaccurate and potentially harmful conclusions.
References
Hubbard, A. K., Spector, L. G., Fortuna, G., Marcotte, E. L., & Poynter, J. N. (2019). Trends in International
Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988-2012. JNCI cancer
spectrum, 3(1), pkz007. https://doi.org/10.1093/jncics/pkz007
Marcotte, E. L., Domingues, A. M., Sample, J. M., Richardson, M. R., & Spector, L. G. (2021). Racial and
ethnic disparities in pediatric cancer incidence among children and young adults in the United
States by single year of age. Cancer, 127(19), 3651–3663. https://doi.org/10.1002/cncr.33678
Spector, L. G., & Birch, J. (2012). The epidemiology of hepatoblastoma. Pediatric blood & cancer, 59(5),
776–779. https://doi.org/10.1002/pbc.24215
University of Minnesota. UofM. (n.d.). Retrieved March 30, 2023, from:
https://med.umn.edu/pediatrics/divisions/epidemiology/research/gametes
Nicole Branch
Hi! I'm originally from Edina, Minnesota and will be graduating this year as a Biology major, Computer Science minor, and Community and Global Health concentrator. During my time at Mac, I've enjoyed working as a computer science preceptor and playing on an intramural soccer team. After graduation, I hope to continue to do work in public health research.