June 2023 | George M. Pikler, M.D., Ph.D., FACP
There is a global epidemic of cancer in young people, and no one knows what’s behind it. Although around 90% of tumors still occur in people aged over 50, young people are increasingly being diagnosed with a range of cancers in many countries.
Higher rates of cancer screening can explain some, but not all, of this increase. Unhealthy diets, obesity, sedentary lifestyles, environmental pollutants and antibiotics are also on the list of likely causes. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity.
The incidence of early-onset colorectal cancer (EO-CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. This surge in young adults is particularly alarming as the overall CRC frequency has been decreasing. EO-CRC is characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left colon-sided location of the primary tumor. Among EO-CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have familial CRC. Most notably, the remaining 50% of EO-CRC patients have neither hereditary syndromes nor familial CRC, thus representing a formidable challenge for research.
In response to increasing incidence rates of EO-CRC, the US Preventive Services Task Force recommends to start average-risk screening at age 45 (vs 50) years. The National Comprehensive Cancer Network [NCCN] recommends that individuals aged <45 years who present with alarming symptoms of CRC (i.e. iron deficiency, rectal bleeding) also undergo screening colonoscopy.
For an individual with ≥1 first-degree relatives with CRC at any age, the recommendation to initiate screening colonoscopy remains at age 40 or 10 years before the earliest diagnosis of CRC in the family. Surveillance in this circumstance should be repeated every 5 years or, if positive, per the findings on colonoscopy. The age for initiation of screening for individuals with second- and third-degree family members with CRC was also lowered from age 50 years to 45 years.
