Younger patients with colon cancer have 3 times as many tumor mutations than older patients with the disease. While this finding may seem bleak, Mohamed E. Salem, MD, assistant professor of medicine at Georgetown Lombardi, and senior investigator of a recent study that will be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, reasons that high levels of mutations in tumors may lead to the creation of better immunotherapies. The more mutations a tumor cell has the more foreign it appears to the immune system, which causes immune fighting cells to easily target tumor cells for elimination.
The researchers looked at distal tumors from 229 patients with colorectal cancer with a median age of 40 years and 503 patients with colorectal cancer with a median age of 71 years. Younger patients had a 3-fold higher tumor mutation load (TML) than older patients. A significantly higher TML was seen in 8.2% of younger patients compared with 2.6% in older patients. There was no difference in the mutation rate of cancer causing genes between older and younger patients.
Genes more frequently mutated in younger patients include HER2, NF1, and the DNA mismatch repair genes MSH6, MSH2, and POLE. The authors reason that mutations in mismatch repair genes may explain the higher tumor load found in younger patients. Mismatch repair genes are responsible for replacing incorrect DNA bases during DNA replication. If mismatch repair genes are nonfunctional then errors in DNA replication go uncorrected, resulting in higher overall mutation rates.
“One of the leading theories for why rates of colorectal cancer are increasing in younger patients relates to lifestyle factors, including diet and exercise,” explains the study’s principal investigator, Benjamin Weinberg, MD, chief hematology/oncology fellow at Georgetown Lombardi. “There is also increasing evidence that bacteria and local inflammation of the colon can drive cancer growth. We can now add tumor mutation load to the list of factors and begin exploring if there is a link between TML and these lifestyle factors.”
1. Salem ME, Xiu J, Lenz HJ, et al. Characterization of tumor mutation load (TML) in solid tumors. Poster Presented at: 2017 American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL. Abstract 11517.