Over 100 New Colorectal Cancer Genetic Risk Factors Identified

A colorectal cancer research study carried out by over 200 scientific collaborators analyzing more than 100,000 cases has identified new genetic risk factors for the disease. Led by the Fred Hutchinson Cancer Center in Seattle and published in Nature Genetics, the study could help clinicians better determine individuals at highest risk so they can receive early screening. The findings may also help identify potential candidates for preventive chemotherapy or other proactive treatments.

“This is the largest, most comprehensive study to date of common genetic risk factors for colorectal cancer,” says Dr. Ulrike “Riki” Peters, molecular and genetic epidemiologist with Fred Hutch and a corresponding lead author of the study. “We’re excited about our study’s discoveries, including the addition of 100-plus genetic risk variants for this severe disease.”

Previous research by Peters and collaborators identified about 140 genetic markers for colorectal cancer. The latest work leverages combined big data and multi-omics analysis to gain additional insights into the underlying biology of colorectal cancer. The researchers conducted a meta-analysis of more than 100,000 colorectal cancer cases compared with a control group of more than 150,000 people without the disease. Both groups were of European or Asian ancestry.

Their initial findings identified 205 independent risk associations for colorectal cancer, of which 50 had not been previously reported. Further multi-omics analysis revealed an additional 53 gene variants linked to the disease.

“Our findings provide new insights into colorectal cancer and substantially expand our knowledge of the role gene variation plays in inherited colorectal cancer,” says Dr. Li Hsu, a biostatistician with Fred Hutch and shared fist author on the study.

Germline genetic risks play a vital role in cancer risk and susceptibility. “Knowing these hereditary factors and which groups are at greatest risk from them can guide clinicians in recommending preventive measures and more frequent screenings which can lead to earlier diagnosis and treatment and better survival outcomes for patients,” says Dr. Minta Thomas one of the first shared authors on the paper and staff scientist at the Fred Hutch. This study findings also validated more commonly known risk factors for CRC, including insulin resistance, smoking and obesity, that have been observed and reported in previous epidemiological studies.

Longer term, Fred Hutch hopes to combine genetic risk data with environmental, dietary and behavioral risk factors to create multifaceted risk scores that more precisely pinpoint a person’s colorectal cancer risk.

Colorectal cancer affects approximately 1.9 million people worldwide annually and is a leading cause of death around the globe. In the U.S., colorectal cancer is the third most diagnosed cancer, excluding skin cancers, according to the American Cancer Society. Overall, the lifetime risk of developing CRC is about 1 in 23 or 4.3% for men and 1 in 25 or 4% for women.

“Colorectal cancer is a serious disease, but it is preventable and can be successfully treated if detected early,” says Dr. William Grady, director of the GI Cancer Prevention Program Clinic and a professor at Fred Hutch. “This study has the potential to pave the way for better screening and prevention, allowing us to improve our current ways of determining who is at higher risk.”