January 6, 2021 | Erin Bluvas, bluvase@sc.edu
The National Human Genome Research Institute has awarded $426K to Feifei Xiao, an assistant professor in the Department of Epidemiology and Biostatistics. She will use the two-year R21 grant to examine the links (e.g., disease risk and mechanisms) between copy number variation and lung cancer.
The study builds on the Human Genome Project, a 13-year international collaboration to identify and map all of the genes of the human genome. Since the project was completed in 2003, many scientists have used this publicly available information to better understand diseases (e.g., genotyping of specific viruses) to tailor treatment, identify mutations linked to various cancers, design medication and better predict its effects, and many other applications (e.g., forensics, biofuels, agriculture, anthropology).
Some of this previous research has already demonstrated that copy number variation (i.e., when the number of copies of a particular gene varies from one person to the next) can play unique roles in many cancer types. For example, it may disrupt gene-coding regions and interfere with the primary or downstream functions of the harbored genes. However, the risk effect and molecular mechanisms of copy number variants is still unclear with regard to lung cancer.
As the second most common cancer (after skin cancer) in the United States, more than 225K new cases of lung cancer are diagnosed each year. Lung cancer is the leading cause of cancer mortality and accounts for approximately 24 percent of all cancer deaths.
“Although genome-wide association studies have identified many lung cancer susceptibility loci, most of its heritability remains hidden and might be further explained by copy number variation,” Xiao says. “Until now, very little research has examined these links, and these studies only looked at a few genes or were based on small sample sizes. Our systematic, large cohort study will provide great insights and new directions in cancer diagnosis, prognosis and therapy.”
For this project, Xiao will partner with Arnold School faculty Guoshuai Cai (environmental health sciences) and James Hardin (epidemiology and biostatistics) along with researchers from Baylor College of Medicine and Laval University. The team expects to find that copy number variants are associated with lung cancer risk and that they regulate gene expression. They also believe these variants may be able to serve as novel biomarkers for the prediction of lung cancer.
To examine these associations, the researchers will utilize datasets from the large-scale Transdisciplinary Research in Cancer of the Lung Consortium, the Lung eQTL Consortium, and two public resources. They will employ innovative, integrative genetics, genomics and bioinformatics approaches based on their interdisciplinary backgrounds.
“We expect that the outcomes from this project will have a significant impact in uncovering the important role of copy number variants underlying human diseases and providing new directions for the risk management and treatment of lung cancer and other diseases,” Xiao says. “Specifically, we hope our findings will facilitate the development of approaches that will identify individuals at risk for lung cancer and new treatment approaches for clinical practice.”