Colorectal Cancer Tumors Differ in Younger vs Older Patients
VIENNA, AUSTRIA—Colorectal cancer (CRC) is on the rise among younger patients. Although some cases of younger-onset CRC can be explained by hereditary factors, most arise spontaneously. Researchers have found that CRC tumors in younger persons may be molecularly distinct from those of older persons, and that these differences are related to the way genes are switched on and off (epigenetics) in the tumors of the younger patients. Such a discovery may lead to better treatment options tailored specifically to a younger age group, the researchers reported at the European Cancer Congress 2015 (ECC2015).
An analysis of genetic mutations in tumors from 126 patients younger than 50 years and 368 patients 50 years and older was presented by Andrea Cercek, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, and assistant professor of medicine at Weill Cornell Medical Center, both in New York, New York.
"Interestingly, we found a different frequency of mutation of genes known to be cancer-causing in the different age groups," she said.
Tumors from two groups of CRC patients were analyzed. The first included patients treated at Memorial Sloan Kettering; and the second, patients from The Cancer Genome Atlas, a project aiming to catalogue cancer-causing genetic mutations, run by the US National Cancer Institute (NCI).
"In the early onset group we found that 154 genes were under-methylated. Both under (hypo-) and over (hyper-) methylation of genes are found in cancer," Cercek explained. "We also found that an increase in methylation went hand in hand with an increase in age among the younger patients, and that this intensification was beyond that which would occur naturally in normal tissue. Finding such a distinctive molecular make-up in this group encourages us to believe that we may, in the future, be able to tailor treatments to them and attempt to prevent or slow down these processes in order to improve outcomes for them."
Younger-onset CRC has increased at a continuous rate of 1.5% per year in men and 1.6% per year in women during the period 1992 to 2011, according to data from the Surveillance, Epidemiology, and End Result (SEER) Registries, the agency that collects and collates cancer statistics on behalf of the NCI. Although CRC is the third most common cancer in the world, with nearly 1.4 million new cases in 2012, diagnoses in younger patients tend to occur later, when the disease is more advanced and hence 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 CRC screening much less frequently than they do older ones," said Cercek. "I believe that raising awareness of the increasing frequency of younger-onset CRC among clinicians is very important."
Younger patients with CRC tend to be treated more aggressively, though currently there is no other difference in the therapies used. "That is why our findings are important," Cercek said. "We hope to be able to continue research on the molecular and epigenetic characterization of tumors from younger-onset CRC patients in order to be able to develop better therapies for them, and improve their overall survival as well as their quality of life."