Case Western Receives $4.9M NIH Award to Investigate Inbred Genetic Susceptibility to Colon Cancer Metastasis

Researchers at Case Wester Reserve University School of Medicine won a $4.9 million NIH grant to fund research into colon cancer patients’ inherent genetic susceptibility to developing metastases. The project aims to determine which genetic variations that patients are born with impact on metastasis rather than focus on genetic variations present in the tumors themselves.

Cancer metastasis has traditionally been thought to arise due to genetic mutations in the cancer cells. The Case Western researchers, however, hypothesize that the risk of metastasis is crucially linked with inbred genetic susceptibility factors. This concept results from prior studies at the university suggesting that colon cancer metastases do not have any additional or different genetic mutations to he primary cancer tumor.

The NIH-funded Case Western program will be led by Markowitz-Ingalls Professor of Cancer Genetics, Sanford Markowitz, M.D., Ph.D. The researchers plan to carry out whole-genome association studies to compare the frequency of over a million genetic variants in patients whose colon cancers have never metastasized, those whose colon cancers were metastatic at the time of diagnosis, and individuals whose colon cancers relapsed and metastasized after initial complete surgical resection.

They hope this approach will allow them to find inherent genetic variations that act impact metastasis susceptibility in different ethnic populations,  determine the biological pathways in which the susceptibility alleles act, and potentially investigate whether these genetic factors also play a role in the likelihood of metastases in other cancers. 

The five-year grant is one of 42 awarded as part of the NIH’s new Transformative R01 program. This has been specifically created under the NIH Roadmap for Medical Research to support exceptionally innovative, high-risk, original, and/or unconventional research projects that have the potential to create or overturn fundamental paradigms.