Among colorectal cancer patients diagnosed before age 50, 16 percent had at least one inherited genetic mutation that increased their risk of developing the disease, according to a study conducted at The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
Importantly, some of these mutations are on genes that are not routinely tested in colorectal cancer patients, meaning that for some patients, their susceptibility cannot be detected with current screening approaches.
“We expected to find a high rate of Lynch syndrome (a hereditary form of colorectal cancer) among these early-onset colon cancer patients. What was surprising were some of the other gene mutations found in the young colorectal cancer patients, including mutations in genes traditionally linked to breast cancer risk, even in patients whose family history was not suggestive of those mutations,” Dr. Rachel Pearlman, the coordinator of the statewide study, said in a press release. “Until multi-gene panel testing, we typically would not have tested a patient with colorectal cancer for mutations in those genes unless they met criteria based on their family history.”
For the study, “Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer,” published in the journal JAMA Oncology, the team analyzed 450 people, ages 17 to 45, who underwent invasive colorectal cancer surgery from Jan. 1, 2013 to June 20, 2016. All were enrolled in the Ohio Colorectal Cancer Prevention Initiative (OCCPI), which aims to screen all state residents newly diagnosed with colorectal cancer.
The researchers collected blood and tumor samples from all the patients. They then screened the tumors for characteristics often seen in Lynch syndrome, such as genetic instability and protein markers found on the cell surface. They also tested all patients for 25 genes that are known to predispose people to develop cancer using a next-generation screening approach. (Lynch syndrome is an inherited condition linked to a high colon cancer risk.)
They identified 75 mutations in cancer susceptibility genes in 72 (16%) of all the patients. A total of 36 patients (8%) had a mutation causing Lynch syndrome only, while two patients (0.4%) had another hereditary cancer syndrome in addition to Lynch syndrome. A total of 34 patients (7.6%) had a different hereditary cancer syndrome, one of whom had two different cancer syndromes.
The results also showed that 33 percent of the 72 patients who had an inherited cancer syndrome did not meet established testing criteria for the gene in which they had a mutation. This means that these people would not normally be tested for mutations in those genes, because they did not meet the testing criteria based on their family history of cancer.
“Our study shows that the spectrum of mutations in early onset colorectal cancer is much broader than we originally thought, both in the number of different gene mutations causing this disease and rates at which they occur,” said Dr. Heather Hampel, principal investigator of the study.
The team advises that all early onset colorectal cancer patients be tested with a multi-gene panel of cancer susceptibility genes, regardless of family history or the results of tumor screening for Lynch syndrome, and offered genetic counseling.
“It is critical that people find out at a young age if they are genetically predisposed to cancer so they can take steps to prevent cancer from occurring at all,” Hampel said. “We believe this data offers additional support for complete genetic testing for all early onset colorectal patients. This could save lives by identifying at-risk families so that they can benefit from intensive cancer surveillance and prevention options.”