Patients aged 45 years or younger with colorectal cancer may have better treatment options available to them because of more mutations in their tumors than older patients, according to research that will be presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).
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Incidence of colorectal cancer in younger patients is rising, especially in the distal colon and rectum areas. Mismatch repair and tumor mutation load are DNA factors that may contribute to more tumors in these areas.
Mohamed E Salem, MD, assistant professor of medicine, Georgetown Lombardi Comprehensive Cancer Center, and colleagues conducted a study to evaluate left-sided colon cancer samples from younger (≤ 45 years; median age, 40) and older patients (≥ 65 years; median age, 71) for mismatch repair and tumor mutation load. Using advanced gene sequencing techniques, researchers determined the tumor mutation load for tissue samples of younger patients (n = 229) and older patients (n = 503) and recorded which genes were most frequently mutated.
Researchers found the most frequently mutated genes among samples from both groups included APC, TP53, KRAS, PIK3CA, ARID1A, FBXW7, SMAD4, ATM, BRAF, and NRAS. No significant difference in the rates of mutations in most cancer-causing genes were recorded between the groups.
However, researchers did find a few genes that were more frequently mutated in younger patients, including HER2, NF1, and the DNA mismatch repair genes MSH6, MSH2, and POLE. DNA mismatch repair mutations could potentially explain the higher tumor mutation load in this younger population, the researchers wrote.
High tumor mutation load was observed in 8.2% of younger patients compared with 2.6% of older patients – more than a 3-fold increase.
Authors of the study concluded that molecular differences between left-sided colon cancer in younger and older patients are mostly due to mismatch repair genes. This biological mechanism, which contributes to a higher tumor mutation load, may explain why younger patients are increasingly diagnosed with colorectal cancer.
Furthermore, authors believe that higher tumor mutation load may predict a higher response rate to immune checkpoint inhibitors in the younger patients, which could expand the pool of immunotherapy treatment options from which to choose.—Zachary Bessette
