Hereditary and Inflammatory Bowel Disease-Related Early Onset Colorectal Cancer Have Unique Characteristics and Clinical Course Compared with Sporadic Disease

Abstract

Background: Early onset colorectal cancer (EoCRC), diagnosed in those <50 years old, is increasing in incidence. We sought to differentiate characteristics and outcomes of EoCRC in patients with sporadic disease or preexisting conditions. Methods: We evaluated 2,135 patients with EoCRC in a population-based cohort from the Canadian province of British Columbia. Patients were identified on the basis of presence of hereditary syndromes (n = 146) or inflammatory bowel disease (IBD; n = 87) and compared with patients with sporadic EoCRC (n = 1,902). Results: Proportions of patients with preexisting conditions were highest in the youngest decile of 18–29 (34.3%, P < 0.0001). Patients with sporadic EoCRC were older, more likely female, and had increased BMI (P < 0.05). IBD-related EoCRC had the highest rates of metastatic disease, poor differentiation, adverse histology, lymphovascular, and perineural invasion (P < 0.05). Survival was lower in patients with IBD (HR, 1.80; 95% CI, 1.54–3.13; P < 0.0001) and higher in hereditary EoCRC (HR, 0.47; 95% CI, 0.45–0.73; P < 0.0001) compared with sporadic. Prognosis did not differ between ulcerative colitis or Crohn's disease but was lower in those with undifferentiated-IBD (HR, 1.87; 95% CI, 1.01–4.05; P = 0.049). Lynch syndrome EoCRC had improved survival over familial adenomatous polyposis (HR, 0.31; 95% CI, 0.054–0.57; P = 0.0037) and other syndromes (HR, 0.43; 95% CI, 0.11–0.99; P = 0.049). In multivariate analysis controlling for prognostic factors, hereditary EoCRC was unchanged from sporadic; however, IBD-related EoCRC had worse overall survival (HR, 2.21; 95% CI, 1.55–3.16; P < 0.0001). Conclusions: EoCRC is heterogenous and patients with preexisting conditions have different characteristics and outcomes compared with sporadic disease. Impact: Prognostic differences identified here for young patients with colorectal cancer and predisposing conditions may help facilitate treatment planning and patient counseling. See related commentary by Hayes, p. 1775

A novel anoikis-related gene prognostic signature and its correlation with the immune microenvironment in colorectal cancer

“…Currently, anoikis resistance correlates with a variety of characteristic tumor processes. Du et al revealed biological interactions between critical elements of anoikis resistance and angiogenesis, which promoted peritoneal metastasis in gastric cancer and showed promise as a potential prognostic biomarker and therapeutic target ( Arif et al, 2021 ). Bárbara et al demonstrated that metabolic remodeling and antioxidant processes in breast cancer can promote anoikis resistance, thus promoting the survival of breast cancer cells at circulating and metastatic sites ( Sousa et al, 2020 ).…”

Colorectal Cancer: From Risk Factors to Oncogenesis

“…A study that tracked individuals diagnosed with early onset colorectal cancer found that patients with a history of inflammatory bowel diseases exhibited higher occurrences of metastatic disease, a reduced degree of histological differentiation, and increased presence of lymphovascular and perineural invasion, in comparison to those with sporadic cancer [ 36 ]. Additionally, these patients experienced lower rates of survival, with statistical significance at a p -value of less than 0.0001 [ 36 ]. The prognosis did not differ between ulcerative colitis and Crohn’s disease, but it was worse for individuals with undifferentiated inflammatory bowel disease ( p = 0.049) [ 36 ].…”

Colorectal Cancer: From Risk Factors to Oncogenesis

“…These authors hypothesized that the chronic inflammation associated with inflammatory bowel diseases could result in a specific genetic profile, which could explain the poor prognosis of this malignant condition [36]. They also noted a higher prevalence of mucinous and signet ring histology (negative prognostic factors) in the inflammatory bowel disease population, as well as higher rates of positive surgical margins [36].…”