January 27, 2022

New fund supports appendiceal cancer research

The newly established Dalton Family Foundation Appendix Cancer Research Fund will support investigations by the Division of Epidemiology at Vanderbilt University Medical Center to better understand this rare malignancy.

Andreana Holowatyj, PhD, MSCI

An initial grant from the Dalton Family Foundation will fund the work of Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine, and colleagues, to identify a hereditary link to appendiceal cancer.

Appendiceal cancer is very rare, affecting about one or two people per million annually. However, the cancer is becoming more common for reasons that are not known.

Last year, Holowatyj and colleagues conducted the first study of appendiceal cancer patterns and survival by race/ethnicity among patients younger than 50 in the U.S. They found poorer disease outcomes among non-Hispanic Blacks compared to non-Hispanic whites, and among men compared with women.

That study, which was published in Gastroenterology, was followed by another investigation led by Holowatyj that compared the molecular landscapes of early-onset and late-onset appendiceal cancer. The second study, published in JAMA Network Open, revealed distinct non-silent mutations in the tumors of younger patients, setting the stage for the development of potential therapeutic advances.

A third study, published in Cancer Epidemiology Biomarkers & Prevention, revealed that one in every three cases of appendiceal cancer occurs in people under age 50 and that these early onset cases have distinct clinical features from those that occur in people over age 50.

The grant supports the next step in Holowatyj’s investigations. She and colleagues will utilize genetics data for patients with appendix cancer to examine the prevalence and spectrum of germline mutations in genes that are linked to an increased lifetime risk for any cancer. They will also search for potential new appendix cancer susceptibility genes by sequencing DNA samples donated by hundreds of appendiceal cancer patients. The findings may help medical professionals identify patients who may benefit from early detection and appendix cancer prevention strategies.

“This grant by the Dalton Family Foundation to support Dr. Holowatyj’s investigations is part of a broader initiative that is funding innovative early-stage research in appendiceal cancer at VUMC, Memorial Sloan Kettering Cancer Center and New York-Presbyterian/Weill Cornell Medical Center,” Mark Dalton said on behalf of the foundation. “It is our hope that early-stage research and collaboration across these premier medical institutions and outstanding scientists will accelerate our understanding and treatment of this rare cancer.”

The burden of rare cancers is magnified due to limited research resources and their cumulative effect. Rare cancers, including primary tumors of the appendix, account for one-quarter of all cancer-related deaths.

“Due to the challenges associated with studying this rare malignancy, many fundamental questions related to appendix cancer etiology and biology remain unanswered. Is there a genetic susceptibility to appendix cancer? Due to the generosity of the Dalton Family Foundation, that’s a question we are well on our way to answering today,” said Holowatyj.