ECC 2015: Discovery of Differences Between Tumors of Younger and Older Patients With Colorectal Cancer May Lead to Better Treatments
Colorectal cancer is on the rise among younger patients. Although some of the younger-onset cases can be explained by hereditary factors, the majority arise spontaneously. Researchers have now found that tumors in younger patients with colorectal cancer may be molecularly distinct from those of older patients and that these differences are related to the epigenetics of the tumors of younger patients. Such a discovery may lead to better treatment options tailored specifically to a younger age group, they said. Their results (Abstract 2189) were presented at the 2015 European Cancer Congress in Vienna, Austria.
Andrea Cercek, MD, Assistant Attending Physician at the Memorial Sloan Kettering Cancer Center and Assistant Professor of Medicine at Weill Cornell Medical Center, described her team’s analysis of genetic mutations in tumors from 126 patients younger thna age 50 and 368 patients older than age 50. “Interestingly, we found a different frequency of mutation of genes known to be cancer-causing in the different age groups,” she said.
Genetic Analysis
Tumors from two groups of patients were analyzed; the first included patients treated at Memorial Sloan Kettering, and the second included patients from The Cancer Genome Atlas. Genomic sequencing techniques were used to look for gene mutations, expressions, and methylation. Patients with very large numbers of mutations, or where the proteins controlling errors of DNA replication were not functioning correctly (microsatellite instability), were excluded.
“In the early-onset group we found that 154 genes were undermethylated. Both hypo- and hypermethylation of genes are found in cancer,” Dr. Cercek explained. “We also found that an increase in methylation went hand in hand with an increase in age among the younger patients, and this intensification was beyond that which would occur naturally in normal tissue. Finding such a distinctive molecular makeup in this group encourages us to believe that we may, in the future, be able to tailor treatments and attempt to prevent or slow down these processes in order to improve outcomes.”
Younger-onset colorectal cancer has increased at a continuous rate of 1.5% per year in men and 1.6% per year in women during the period 1992–2011, according to data from the Surveillance, Epidemiology, and End Result Registries (SEER).
Underdiagnosis in Young Patients
Although colorectal cancer is the third most common cancer in the world, with nearly 1.4 million new cases diagnosed in 2012, younger patients tend to present and be diagnosed later, when their disease is more advanced and more difficult to treat. This is most likely due to a lack of awareness of symptoms in patients as well as doctors, in addition to the tendency to attribute those symptoms to other causes.
“Changes in bowel habits may be attributed to Crohn’s disease, food allergies, or simply stress, for example, and doctors send younger patients for early colorectal cancer screening much less frequently than they do older ones,” said Dr. Cercek. “I believe that raising awareness of the increasing frequency of younger-onset colorectal cancer among clinicians is very important.”
Younger colorectal patients tend to be treated more aggressively, although currently there is no other difference in the therapies used. “That is why our findings are important,” Dr. Cercek concluded. “We hope to be able to continue research on the molecular and epigenetic characterization of tumors from patients with younger-onset colorectal cancer in order to be able to develop better therapies for them and improve their overall survival as well as their quality of life.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
