Yaohua Yang, PhD
Yaohua Yang, PhD, an assistant professor in the Department of Genome Sciences, and his research team published a landmark article on tissue-specific DNA methylation and cancer risk in the journal Nature Communications in July 2024. This pioneering research offers critical insights into the genetic and epigenetic underpinnings of seven distinct cancers.
Cancer is a leading cause of death worldwide, with about 33% of the risk coming from inherited factors. One key feature of cancer cells is unusual DNA methylation patterns, which can influence how genes are turned on or off. However, the exact risks linked to these changes have been unclear.
Dr. Yang’s team addresses this challenge by using data from the Genotype-Tissue Expression (GTEx) consortium. They established genetic models to predict DNA methylation in normal tissues across seven different types. Then, they applied these models to study DNA methylation in various cancers, including breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers.
“Our analysis identified over 4,000 DNA methylation sites (CpGs) linked to cancer risk,” said Dr. Yang. “Interestingly, about 95% of these sites were specific to individual cancer types. We also discovered 92 new regions in the genome significantly associated with cancer risk even after considering known factors.”
The team further performed comprehensive multi-omics analyses and found 854 DNA methylation-genes-cancer trios. “These trios suggest that changes in DNA methylation could influence cancer risk by affecting gene expression,” Dr. Yang explained.
These novel findings help Dr. Yang and his team understand how genetic and epigenetic factors interact in cancer development, offering new ways to potentially reduce cancer risk through epigenetic mechanisms.
Dr. Yang led this innovative project in collaboration with investigators from Vanderbilt University Medical Center. The study was supported by multiple grants from the National Institutes of Health (NIH), including R00CA248822 (PI: Yang), R01CA249863 (MPIs: Cai & Long), and R01CA247987 (MPIs: Long & Ye).
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