Colorectal cancer rates in patients younger than 50 are climbing, leaving researchers scrambling to understand why. To this end, two research centers have launched that are devoted to studying early-onset disease: The centers will treat younger patients—and advance research efforts by gathering comprehensive data on every aspect of their disease.

Although the overall incidence of colorectal cancer in the United States has been steadily declining over the past few decades, it has been climbing by 1% to 3% a year in patients younger than age 50. “The question is, why is this happening?” says Andrea Cercek, MD, co-leader of the Center for Young Onset Colorectal Cancer at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY.

Aiming to answer that question, Jonathan Loree, MD, of BC Cancer in British Columbia, Canada, and colleagues set out to characterize the clinical and molecular differences between early- and average-onset colorectal cancers. They analyzed data from 36,371 patients that included clinical presentation and molecular and genomic information. They found that patients younger than age 50 were more likely to have microsatellite instability, to be diagnosed with metastatic disease, and to develop primary tumors in the distal colon or rectum; they were less likely to have BRAF V600 mutations. Moreover, early-onset patients also had different prevalence of previously established consensus molecular subtypes of disease based on age.

The results, says Loree, emphasize the heterogeneity of early-onset disease and broadly outline the molecular differences between early-onset and average-onset colorectal cancer.

Although the study does not definitively explain how the disease differs in younger patients, “it does propose a few interesting findings that warrant further investigation,” says Cercek, who was not involved in the study.

Such investigation is ongoing at the MSKCC center, the first to specialize in early-onset disease when it opened in 2018. A second center for patients with the disease opened in March 2019 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) in Boston, MA.

“We just felt like we needed to do a better job taking care of these patients—as well as do a better job trying to research why this is happening and whether these cancers that develop in young people are different biologically than the cancers that develop in older patients,” explains Kimmie Ng, MD, MPH, director of the DF/BWCC practice.

Patients treated at the DF/BWCC center will join a prospective study in which researchers will gather comprehensive clinical, treatment, and survival data, along with tumor, blood, and stool samples and information about diet and lifestyle. Patients will receive personalized care based on genomic sequencing, and can consult with experts on issues such as fertility preservation. The center will also work to increase awareness and education about early-onset disease, which is often overlooked by clinicians, leading to delays in diagnosis.

Both Ng and Cercek are especially interested in sporadic disease, which lacks a known cause, such as family history, a genetic driver, or a predisposing condition, and accounts for most early-onset cases; patients with sporadic disease often don't have other typical risk factors, such as a sedentary lifestyle or poor diet, either. “That's really the population that needs a very good, deeper look at their tumor genomics, and their genetics as well,” Cercek says.

Characterizing the molecular and biological underpinnings of early-onset colorectal cancer would likely help oncologists understand why it is becoming more common—an important step in improving prevention, screening, early detection, and treatment. “If we just knew why this is happening, we could address it from so many different angles,” Ng says. –Catherine Caruso

©2019 American Association for Cancer Research.
2019
American Association for Cancer Research.