Tumors of younger patients with early-onset colorectal cancer (CRC) differ from the tumors of those diagnosed with CRC later in life, both genetically and epigenetically, according to a study presented at the 2015 European Cancer Congress (ECC) in Vienna (abstract 2189).
Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York, and colleagues found that 154 genes were hypomethylated among younger patients with early-onset tumors. Increased methylation was observed with increasing age among younger patients diagnosed with CRC.
An uptick in the incidence of sporadic, non-hereditary CRC in patients younger than age 50 has recently been observed. Younger-onset CRC has been increasing at a rate of 1.5% and 1.6% every year for men and women, respectively, between 1992 and 2011 according to data from the Surveillance, Epidemiology, and End Results (SEER) registries.
To understand whether the tumors that arise in younger patients are molecularly distinct from those of older patients, Cercek and colleagues performed a pilot study, analyzing the genomes of CRC tumors from 126 patients age 50 or younger and compared these with the CRC tumor genomes of 368 patients older than age 50. The authors assessed both the genomic sequences and the genome-wide DNA methylation patterns of the samples. CRC patients with tumors with high numbers of mutations or microsatellite instability were excluded from the analysis.
The study found that several cancer-causing genes—including ATRX, DIS3, RAD52, and SMO—had different mutation frequencies between the two age cohorts.
The addition of methyl groups to DNA is an epigenetic marker that can influence gene expression. Hypermethylated DNA regions suppress gene transcription, resulting in gene silencing; this is a normal feature of genomes, but certain patterns of hypermethylation can be associated with tumors. Widespread hypomethylation can also be a marker of an abnormality of cancer genomes.
“It appears from the analysis that patients with early-onset CRC [those diagnosed at an earlier age] have hypomethylated tumor genes beyond what we would expect to see with aging,” Cercek told Cancer Network. While these results are so far descriptive, “they strongly suggest that the tumors are different and thus may have different biology,” Cercek added.
Patients diagnosed at a younger age typically have later-stage disease that is more refractory to treatment. The reason for the later diagnosis in younger patients may be because symptoms of the disease are typically attributed to other causes.
According to Cercek, better awareness among clinicians and younger individuals may result in earlier diagnosis and better treatment of CRC. The authors are currently expanding their dataset to further explore these molecular differences in CRC tumors based on age of diagnosis.