Due in part to improvements in screening, the rates of new colorectal cancer diagnoses have been falling in the United States for people ages 50 and older. However, for people under 50, for whom routine screening is not recommended, rates are increasing significantly. Now, a study from researchers at the University of Colorado shows genetic differences between colorectal cancer (CRC) in young and old patients, pointing toward different treatments and strategies in combating the young form of the disease. The study was presented at the 2016 Genitourinary Cancers Symposium.
Previous studies show that most colorectal cancers are considered sporadic, meaning the genetic changes develop by chance after a person is born, so there is no risk of passing these genetic changes on to one’s children. Inherited colorectal cancers are less common (about 5%) and occur when gene mutations are passed from one generation to the next. Often, the cause of colorectal cancer is not known. However, the increasing incidence of CRC among young adults is thought to be linked to rapidly increasing obesity rates in the United States, obesity is a major risk factor for colorectal cancer. Recent studies have also shown that CRC in patients younger than 50 years old tends to be more aggressive than CRC in older patients. Therefore, the current study seeks to investigate the genetic cause of more aggressive behaviour in the young form of the disease.
The current study compared 9 tumours from younger patients, whose median age was 31, with 9 tumours from older patients, whose median was age 73. The lab sequenced 45 million ‘reads’ from each of the tested tumours, showing 141 genes that are enriched in samples from younger patients and a largely different cohort of 42 genes enriched in samples from older patients. Results show distinct genetic differences between younger and older patients with colorectal cancer.
Results show that many of the enriched genes in samples from younger patients are involved in signaling pathways ERBB2, NOTCH3 and CAV1, which are known to spur cell proliferation commonly associated with cancer. In contrast, data findings show that pathways enriched in samples from older patients included CDX2, HMGB3 and EPHB2, which are primarily involved in cell differentiation, which is the ability or inability of cells to move from stem-like cells to more specialized tissues. The group note that the enrichment of ERBB2 (Her2/neu) in samples from younger patients is an especially interesting target given that there are FDA-approved therapies that target this particular gene.
The team surmise that they have gathered the important resource of tumour samples grown from the tissues of young CRC patients, allowing further preclinical genetic and drug testing. For the future, the researchers plan to validate the findings of these differences in a larger patient population. They go on to add that if these pathways prove to be important drivers of CRC in young patients, they hope to explore trials of drugs targeting these potential tumour drivers.