Clinicopathological Characteristics of Early Onset Colorectal Cancer

Fanny E. R. Vuik; Stella A. V. Nieuwenburg; Iris D. Nagtegaal; Ernst J. Kuipers; Manon C. W. Spaander


Aliment Pharmacol Ther. 2021;54(44512):1463-1471. 

In This Article

Abstract and Introduction


Background: The rising incidence of early onset colorectal cancer (EOCRC) might reflect a novel tumour entity.

Aims: To evaluate clinicopathological characteristics of sporadic EOCRC (in patients < 50 years old) and investigate changes over time

Methods: All patients with sporadic EOCRC between 1989 and 2016 were included and divided by age: 20–29 years (group I), 30–39 years (group II) and 40–49 years (group III).

Results: We included 6400 patients. The presence of signet-ring cells and more poorly differentiated tumours were more common in the younger age groups: 5.4% and 3.7% for signet-ring cells in group I and II vs 1.4% in group III (P < 0.01), and 28.5% and 20.3% for poorly differentiated in group I and II vs 16.6% in group III, (P < 0.01 group I; P = 0.07 group II). Positive lymph nodes were more frequently observed in the younger age groups: 16.2% in group I vs 9.3% in group II (P = 0.01) and 7.9% (P < 0.01) in group III. Over time, a greater proportion of CRCs were diagnosed in women in group I (34.5% < 2004 vs 54.9%>2005, P = 0.09), and a higher percentage of rectal cancer was found in age group III (34.3% < 2004 vs 40.7% > 2005, P < 0.01). Mean overall survival was 6.3 years and improved over time.

Conclusions: EOCRC is not only characterised by age of onset but also by the more frequent presence of signet-ring cells, more poorly differentiated tumours, and higher risk of lymph node metastases. In the most recent years, a higher proportion of rectal cancer was found from the age of 30 years, and a higher proportion of CRCs were diagnosed in females below the age of 30 years.


Colorectal cancer (CRC) incidence and mortality are decreasing in adults older than 50 years due to screening and improvements in CRC treatment in both the US and Europe.[1,2] Conversely, CRC incidence in young adults, early-onset CRC (EOCRC), is rising in several parts of the world.[2,3] It is known that individuals with Lynch syndrome (LS) or familial adenomatous polyposis (FAP) are more likely to develop CRC at a relatively young age. However, this group accounts for only 2%-3% of all CRC cases.[4] Most of EOCRCs are sporadic cases. The underlying factors contributing to the increasing incidence of sporadic CRC in young adults are still incompletely understood but seem to include obesity, lack of physical activity, alcohol intake and cigarette smoking.[5–7] Also, several drugs have been reported to be associated with CRC risk. The use of oral antibiotics is associated with an increased CRC risk, while the use of statin and aspirin might decrease this risk.[8–10] Association studies on sporadic EOCRC show that male gender, being black or Asian, having inflammatory bowel disease (IBD) or a family history of CRC might be associated with an increased EOCRC risk.[11] To fully elucidate causes and mechanisms of EOCRC, it is important to have more insight into both patient and tumour characteristics of these CRCs. Data on location, histology, and tumour stages of sporadic EOCRC compared to late-onset CRC are scarce and conflicting. Some studies indicate a higher prevalence of right-sided CRC in EOCRC while other studies showed a higher prevalence of a more distal location.[12,13] Signet-ring cells were described to be more prominent in EOCRC, while conflicting studies were published on KRAS, NRAS and BRAF mutations among EOCRC patients.[14,15] These conflicting data might be a result of differences between and within EOCRC cohorts. For example, the very young patients (below the age of 30 years) might have a different type of CRC than the slightly older EOCRC patients (30–50 years of age). The latter might resemble more the sporadic CRC in adults above the age of 50 years of age. Furthermore, it is questioned whether the rising incidence of sporadic EOCRC might reflect the rise of a novel tumour entity. Therefore, the aim of this study was to assess the clinicopathological characteristics of sporadic EOCRCs within different age categories (20–29 years vs 30–39 years vs 40–49 years) and investigate changes over time.