More than 100 new genetic risk factors for CRC identified

Researchers at the Fred Hutchinson Cancer Center, performing a broad and comprehensive analysis of more than 100,000 cases of colorectal cancer (CRC) have identified more than 100 new genetic risk factors strongly linked to the disease.

The resultsPosted in Natural genetics, demonstrating the power of using big data, combining large-scale study with complex and detailed analysis using multi-omics, to gain additional insights into the underlying biology of colorectal cancer. The researchers also help their data could be used as the basis for developing early screening strategies to identify at-risk patients, while potentially suggesting the best treatment options for those diagnosed with CRC.

“This is the largest and most comprehensive study to date of common genetic risk factors for colorectal cancer,” said Ulrike “Riki” Peters, PhD, molecular and genetic epidemiologist at Fred Hutchinson and author. principal of the study. “We are excited about the findings of our study, including the addition of over 100 genetic risk variants for this serious disease.”

The new research aimed to add to the body of knowledge about CRC, which to date has identified 150 statistically independent risk variants via genome-wide association studies (GWAS). For this study, Peters and more than 200 colleagues from various research centers focused on genetic and environmental risk factors for CRC, and included the impact of race and ethnicity on genetic risk factors under underlying common and complex diseases. The team’s previous work had identified around 140 genetic markers for colorectal cancer.

Investigators conducted a meta-analysis of 100,204 colorectal cancer cases and 154,587 controls without the disease. Both groups were of European or Asian descent. “We complemented the GWAS with transcriptome- and methylome-scale association analyzes (TWAS and MWAS),” the researchers wrote.

Early results from the study identified 205 independent risk associations for colorectal cancer, 50 of which had not been previously reported. TWAS and MWAS revealed 53 additional disease-related genetic variants. The study was twice as large as CRC’s previous GWAS and the mixed ethnicity of the groups – including both European and Asian ancestry – demonstrated that most loci are shared between the groups.

The results also validated more well-known risk factors for CRC, including insulin resistance, smoking and obesity, which have been observed and reported in previous epidemiological studies.

Colorectal cancer is one of the leading causes of death worldwide. “Colorectal cancer is a serious disease, but it is preventable and can be successfully treated if detected early,” said William Grady, MD, clinical director of the Gastrointestinal Cancer Prevention Program and professor at Fred Hutch. “This study has the potential to pave the way for better screening and prevention, allowing us to improve our current means of determining who is most at risk.

“Germline genetic risks or genetic mutations – those you inherit from your biological parents – play a vital role in cancer risk and susceptibility. “Knowing these hereditary factors and the groups most at risk can guide clinicians in the recommending preventative measures and more frequent screenings that can lead to earlier diagnosis and treatment and better survival outcomes for patients,” emphasized co-first author Minta Thomas, PhD, a Fred Hutch scientist working with Hsu and Peters.

Based on their findings, the researchers and collaborators now plan to use the results to develop germline DNA-based tests that can categorize people at high genetic risk for colorectal cancer and those with only a low probability. minimum to develop the disease.

A longer-term goal is to combine genetic risk data with other risk factors – environmental, dietary, and behavioral (such as smoking) – to create multifaceted polygenic risk scores (PRS) to determine more precisely the risk of developing CRC.