Genomic similarities and differences in early onset colorectal cancer
A new study looked at the genetic characteristics of metastatic colorectal cancer diagnosed before age 50 and compared them with colorectal cancer diagnosed at older ages. The study included 1,892 patients treated at Samsung Medical Center in South Korea, including 376 people with early onset colorectal cancer.
Overall, the researchers found that early onset colorectal cancer has a very similar genomic profile to colorectal cancer diagnosed at older ages. The most common genetic alterations, including TP53, APC, and KRAS, occurred at similar rates in both groups.
There were some differences in other molecular features. High tumour mutational burden was less common in early onset colorectal cancer, occurring in 14.6% of younger patients compared with 19.3% of patients with average onset disease. Tumour mutational burden refers to the number of genetic changes found within a tumour’s DNA. A high tumour mutational burden can sometimes affect how the immune system recognizes and responds to cancer.
In contrast, high microsatellite instability was slightly more common in early onset colorectal cancer, occurring in 2.7% compared with 1.7%. Microsatellites are short, repeated sequences of DNA. Microsatellite instability occurs when the system that normally repairs mistakes in DNA does not work properly, allowing these repeated sequences to become altered. High microsatellite instability can be an important feature of colorectal cancer because it may affect how the cancer behaves and how it responds to certain treatments, including immunotherapy.
Among people with microsatellite stable early onset colorectal cancer, the genetic changes were mainly driven by the same common colorectal cancer genes, including TP53, APC, and KRAS. Tumours with high microsatellite instability showed a more varied pattern of genetic alterations.
One notable difference was that MYC alterations were more common among people with early onset colorectal cancer, occurring in 15.7% of younger patients. The researchers also found that some genetic alterations were more common among the youngest patients within the early onset group, suggesting that there may be additional biological differences associated with very young age at diagnosis.
The findings suggest that early onset colorectal cancer is not a completely distinct genetic form of colorectal cancer, but there may be certain biological differences among people diagnosed at younger ages. More research is needed to understand what these differences mean and whether they could even
