A closer look at gene-environment interactions in CRC
Peters and biostatistician Dr. Li Hsu also received a five-year, $4.4 million grant from the NCI to further investigate colorectal cancer risk. Last year, Peters’ team and collaborators published a study of 100 new genetic risk variants for the disease.
they are going to investigate now Gene-environment interaction Conduct research in diverse populations using integrative omics approaches.
“Little is known about the extent to which environmental risk factors such as lifestyle, diet, obesity, drug use, and other factors alter genetic risk, or vice versa,” Peters says. he says. “We urgently need a comprehensive approach that combines high-dimensional multi-omics data with diverse, large and well-characterized study populations and new statistical approaches.”
Identifying precisely which environmental factors influence genetic risk will not only provide important biological insights, but also provide guidance for actionable targets for individualized screening and intervention. can be provided. Multi-omics approaches, including single-cell techniques, have helped uncover cell type-specific biological processes and how environmental risk factors and genetic variation influence disease development. .
However, a lack of data on gene regulation in non-European populations is hampering progress.
The NCI grant will allow researchers to profile colorectal samples taken from 50 racially and ethnically diverse healthy participants, as well as glucose, insulin, interleukin-6 and C responses. This makes it possible to investigate “intermediate biomarkers” related to colorectal cancer, such as inflammatory markers such as sexual proteins.
“We plan to use genetic instruments to predict biomarkers associated with metabolic dysregulation and inflammation, two important risk factors for colorectal cancer, and incorporate them into gene-environment analyzes along with measured exposures. “,” Hsu said.
The resource includes a dataset containing 99,000 colorectal patients and 140,000 healthy participants or “controls,” including over 21,000 cancer patients and 35,000 non-control participants. It’s European.
“These data will be integrated with single cell and existing biobank data, state-of-the-art resources and technology to perform comprehensive function-based genomic genetic and environmental testing and risk predictive analysis.” Peters he said. “We are developing functionally informed, genome-wide gene-environment analysis across the spectrum of key environmental risk factors, including obesity, diabetes, smoking, alcohol, drug use, diet, and associated intermediate biomarkers. By conducting interaction scans, we hope to discover new interactions in “metabolic dysregulation and chronic inflammation.” ”
Ultimately, Peters, Hsu and colleagues will integrate functional single-cell omics data into the world’s largest CRC genetic epidemiology database to determine the extent to which modifiable risk factors influence genetic risk for colorectal cancer. Planning to gain a deeper understanding of giving (and vice versa).
The results of this study are expected to impact colorectal cancer prevention by guiding lifestyle interventions, personalizing screening decisions, and ultimately reducing the burden of this cancer. .
