Clinical Pearls & Morning Reports

By Carla Rothaus

Published April 20, 2022


What are some of the proposed risk factors for early-onset colorectal cancer?

Patients with early-onset colorectal cancers are often unaware of this disease and its symptoms, which are frequently attributed to common, benign conditions. Read the NEJM Review Article here.

Clinical Pearls

Q: How common is early-onset colorectal cancer?

A: An alarming increase in cases of early-onset colorectal cancer, defined as diagnosis in patients younger than 50 years of age, has occurred in the United States and other high-income countries over the past few decades. The incidence of early-onset colorectal cancer is projected to steadily increase and more than double by 2030. Early-onset colorectal cancer now accounts for approximately 10% of all new diagnoses of this cancer, and an accompanying increase in colorectal cancer–related mortality during the past decade has also been observed among younger patients. Early-onset colorectal cancers are more likely than later-onset cancers to display high-frequency microsatellite instability, which is strongly associated with poor tumor differentiation.

Q: Do clinical features of early-onset colorectal cancer differ from those of later-onset disease?

A: Clinical features of early-onset colorectal cancer differ from those of later-onset disease. Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation. By comparison, later-onset colorectal cancers (those diagnosed in patients ≥50 years of age) occur at similar frequencies in the proximal colon and distal colorectum. A more advanced tumor–node–metastasis stage of disease (i.e., stage III or IV) at diagnosis is more likely in patients with early-onset colorectal cancer than in patients who have later-onset disease, as shown in studies that included large, population-based cohorts.

Morning Report Questions

Q: What are some of the proposed risk factors for early-onset colorectal cancer?

A: Although a primary or predominant risk factor accounting for the worldwide increase in early-onset colorectal cancer has not been found, a multifactorial risk profile is probably responsible, including lifestyle and environmental exposures over several decades that can alter the gut microbiome. Data suggest a considerable overlap with risk factors for later-onset colorectal cancer, including a Western-style diet, which can alter the gut microbial composition, resulting in dysbiosis and chronic inflammation. Data from an observational study and a prospective cohort study showed that obesity in adolescence was associated with an increased incidence of early-onset colorectal cancer and related mortality. Antibiotics are known to substantially alter the gut microbiome, and prolonged use of these agents may be a risk factor for early-onset colorectal cancer. Somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment.

Q: What can be done to combat the rising incidence of early-onset colorectal cancer?

A: The challenges and barriers to compliance with guidelines for colorectal cancer screening must be addressed for younger adults, as well as for persons at average risk who are 50 years of age or older. The most important factor for improving adherence to screening guidelines is a physician’s recommendation. Primary care physicians should tailor screening recommendations, including noninvasive, stool-based tests, on the basis of patients’ preferences. Obtaining and updating family history data are important in the identification of patients at high risk, for whom individualized screening guidelines can be implemented. Universal testing of colorectal cancers for the Lynch syndrome is an important step forward, as is the recommendation of germline multigene panel testing for all early-onset colorectal cancers. A new screening approach is the assessment of circulating tumor DNA in blood plasma for the detection of early-stage colorectal cancer. If this approach is found to be successful in clinical trials, it has the potential to increase screening rates.

Browse more Clinical Pearls & Morning Reports »

NEJM Knowledge+