Dr. Thornton works to develop new statistical methods to analyze the associations between genes and complex traits, particularly in situations complicated by the fact that people in the study are related to one another and/or are of mixed ancestry.

Dr. Thornton studied math at Hampton University, a historically Black university in Virginia. He earned his Ph.D. in Statistics from the University of Chicago, where his research was focused on new methods for genetic analyses. After leaving Chicago, he was a postdoctoral fellow at the University of California, Berkeley, and then at UC San Francisco. He joined the Department of Biostatistics at the University of Washington in 2009. Since 2016, he has also been the Robert W. Day Endowed Professor of Public Health at UW.

It is well-recognized that genetics play a role in how different people respond to medications, particularly in cancer patients. On the other hand, we are a long way from having those connections be concrete enough to act on them in the clinical setting. One particularly large limitation is that the majority of studies focus on people of European ancestry, which means we know a lot less about everyone else.

In a recent paper, Dr. Thornton and colleagues recruited indigenous women being treated for breast cancer with the drug tamoxifen. These women were being treated either at the Alaska Native Medical Center in Anchorage or at the Confederated Salish and Kootenai Tribes Tribal Health Department in NW Montana. All had estrogen-positive tumors, meaning that the tumor relies on signals from estrogen to survive. Tamoxifen is effective against estrogen-positive tumors because it blocks the estrogen receptor on the tumor cells - preventing the tumor from getting the survival signal from estrogen.

From previous studies, we know that tamoxifen is activated by a group of enzymes in the body called CYPs and that variation in CYP genes can predict how effective tamoxifen is as a chemotherapy. But Dr. Thornton and his collaborators wanted to know if that held true for American Indian/Alaska Native women as well. They used DNA samples to find variation in the CYP genes, and simultaneously looked at blood samples to measure how much active tamoxifen there was. They found that which version of the CYP2D6 gene a woman had was the most useful for predicting how much tamoxifen she had in her bloodstream. They also determined how common the different versions of CYP2D6 were in their sample of these two populations.

Based on their results, the authors suggest that clinicians should do genetic testing for these CYP variants before prescribing tamoxifen. Given that some patients will be less able to activate the drug, those patients might need to be given a higher dose to make up for that or they might benefit from being prescribed a different treatment instead.