While it is widely known that inherited or acquired genetic mutations can cause cancer, the link between mutations and cancer is not always well understood. This is particularly true for the over a thousand newly discovered mutations in non-coding regions of the human genome.
A researcher recruited to Baylor College of Medicine is now studying the molecular and cellular mechanisms that link environmental toxins and inherited mutations to the development of cancer. Yong Li was recruited in 2019 from the Cleveland Clinic Lerner College of Medicine, where he was professor of medicine. He was awarded an Established Investigator Award from CPRIT.
Li focuses on unsolved questions in cancer etiology, or origin. For example, glyphosate, know by its brand name RoundUp®, is one of the most widely used herbicides, and Texas is one of the top eight states for glyphosate use. There is some evidence from epidemiological studies that glyphosate exposure is linked to certain cancers, but Li is looking for the mechanism by which that happens.
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While it is widely known that inherited or acquired genetic mutations can cause cancer, the link between mutations and cancer is not always well understood. This is particularly true for the over a thousand newly discovered mutations in non-coding regions of the human genome.
A researcher recruited to Baylor College of Medicine is now studying the molecular and cellular mechanisms that link environmental toxins and inherited mutations to the development of cancer. Yong Li was recruited in 2019 from the Cleveland Clinic Lerner College of Medicine, where he was professor of medicine. He was awarded an Established Investigator Award from CPRIT.
Li focuses on unsolved questions in cancer etiology, or origin. For example, glyphosate, know by its brand name RoundUp®, is one of the most widely used herbicides, and Texas is one of the top eight states for glyphosate use. There is some evidence from epidemiological studies that glyphosate exposure is linked to certain cancers, but Li is looking for the mechanism by which that happens.
Although the carcinogenicity of RoundUp® is hotly debated, Bayer, the company that produces it, recently proposed a $10.9 billion settlement to compensate nearly 100,000 patients who developed non-Hodgkins lymphoma after glyphosate exposure. Bayer has not added warning labels to its product.
Glyphosate exposure is statistically linked to another type of immune system cancer, multiple myeloma. "Both non-Hodgkins lymphoma and multiple myeloma are B-cell cancers," Li says. "So there may be some B-cell–specific mechanism for glyphosate to induce cancer in these cells."
Li is using mouse models to ascertain the carcinogenicity of glyphosate in B-cell cancers and hopes to associate the epidemiological observations with molecular mechanisms. He thinks that understanding the etiology will lead to better prevention, clinical care, and environmental regulations.
"I don’t think the EPA limit is set correctly," he says. "I hope my research can inform the regulatory agency to set a better acceptable daily intake level for glyphosate."
Li’s other research involves a genetic risk factor for multiple cancers carried by six million Americans. This mutation involves a single nucleotide substitution in the non-coding region of a tumor-suppressor gene called TP53. The relative risk for any one person with this mutation developing cancer is low but it’s still substantial, he says. Li is using mouse models to review its role in cancer initiation and development, particularly in pediatric and adult leukemias.
He is also examining tissue samples from cancer patients to study the relationship between the TP53 mutation in concert with other mutations and the development of cancer. While not everyone with the mutation will develop cancer, in certain families additional mutations may increase risk. So if a family member develops leukemia, for example, other family members should be screened and plan regular surveillance, he says.
Li says, "I hope my research on cancer etiology will provide information on cancer risk and potential treatment strategy for all Texans and all Americans." He adds that CPRIT’s investment "will allow me to take a much broader view of cancer etiology in terms of the breadth and depth of my research. This grant allowed me to buy equipment that I can use in my laboratory rather than go to another facility." He noted that this was especially helpful during the pandemic.
Li received his undergraduate education at Lanzhou University in China, and his Ph.D. in biochemistry & cell biology from the Chinese Academy of Sciences. He came to the U.S. as a postdoctoral fellow at Yale University in 1999. He joined the faculty of the University of Louisville School of Medicine in 2004, and moved to the Cleveland Clinic in 2014.
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