by Cora A. Hersh
DCEG welcomed Dr. Douglas Easton, Professor of Genetic Epidemiology in the Department of Public Health and Primary Care and the Department of Oncology at the University of Cambridge, Cambridge, U.K., as a Visiting Scholar in March 2017. He leads a highly influential research group on genetic susceptibility to cancer, and coordinates large international breast cancer consortia; Dr. Easton is internationally recognized for his discovery of genetic susceptibility loci for breast cancer risk.
“I have worked with Dr. Easton since the formation of the Breast Cancer Association Consortium (BCAC) in 2005. Under his leadership, this consortium has identified the majority of over 170 common susceptibility loci for breast cancer,” said Deputy Director Montserrat Garcia-Closas, M.D., Dr.P.H., who hosted the visit.
In a division-wide seminar titled “Susceptibility to breast cancer, common and rare: How far have we gone and where next?”, Dr. Easton outlined the state of the science on heritable factors for this malignancy, and described the major international efforts to identify other genetic variants that may contribute to risk, including large-scale array genotyping systems such as iCOGS and OncoArray.
The scientific community’s understanding of heritable breast cancer risk has come a long way in recent years, yet 41% of familial risk is still unexplained. Dr. Easton emphasized that there is much more work to be done to discover which genetic variants are important in determining breast cancer risk, especially with increasing demand for clinical applications of risk estimates.
Dr. Easton described modern strategies for identification of risk loci that he views as particularly promising. Some examples were fine mapping to pinpoint specific single-nucleotide polymorphisms (SNPs) independently associated with cancer risk, and growing efforts to sequence the tumors to reveal interactions between somatic and germline mutations in breast cancer etiology.
Using the findings from such studies, Dr. Easton and colleagues calculate individual polygenic risk scores (PRS), an account of all known genetic characteristics that affect breast cancer risk. Compared to other approaches that consider only lifestyle factors or breast density, total PRS is very effective in predicting risk.
During his two-day visit, Dr. Easton participated in several meetings with special interest groups at DCEG. Dr. Garcia-Closas hosted discussions on improving breast cancer risk stratification in the general population and on the status and challenges of genome-wide association studies for other cancers. In addition, DCEG investigators hosted a discussion on tissue composition, somatic alterations, and breast cancer risk and progression, and another on the value of circulating blood biomarkers.
Finally, Dr. Easton attended an informal lunch with fellows, organized by postdoctoral fellow Maeve Mullooly, Ph.D., M.P.H. He shared career advice and his thoughts on the current “big questions” in breast cancer research.