Colonic neoplasia and celiac disease: A systematic review

Celiac disease (CD) is a chronic inflammatory disease that affects multiple systems in genetically predisposed individuals. The only known treatment for CD is adherence to a gluten-free diet. Gluten has been found to exert deleterious immune-inflammatory effects beyond the small bowel, involving several genetic, cellular, and paracellular mechanisms in the context of chronic inflammation, leading to colorectal carcinoma (CRC) in CD patients. Several neoplasms, including adenocarcinoma and lymphoma, are associated with CD. Despite strong evidence of an association between CD and small intestinal malignancies, CRC is less common and underdiagnosed in patients with CD. In practice, most CD patients are only monitored for small bowel complications despite mild lower gastrointestinal symptoms; thus, colonoscopy is underused, with a greater focus on upper endoscopy and small bowel biopsy, a major hindrance in early diagnosis. Delayed diagnosis and poor prognosis have also been linked to nonspecific symptoms and late presentations. The lack of screening guidelines appears to be a critical gap due to disconnection between CD and heterogeneous expression of the disease complications add further diagnostic delay.

To critically evaluate and synthesize existing evidence on the association between CD and CRC to encourage early-stage detection through lower gastrointestinal screening in CD patients and suggest individual-specific management strategies.

The Scopus, Web of Science, and PubMed databases were searched via Medical Subject Headings words related to the criteria pertinent to CD and colon cancer/neoplasm, with a focus on pathophysiological mechanisms, clinical presentations, and outcomes reviewed.

A total of 3028 citations related to CD and neoplasia were initially identified. Following a critical review and exclusions, 136 citations were suitable for inclusion in this study. Despite its low incidence, a clinically significant association was found between CRC and CD that could impact the overall patient survival rate, suggesting early screening investigations, individual-specific interventions, and further longitudinal studies.

A low incidence of colon lymphoma and adenocarcinoma has been revealed. The clinical presentation of colon lymphoma and adenocarcinoma is indolent and nonspecific, with late presentation in the form of adhesions and perforation. A modest but statistically significant increase in CRC risk among CD patients was noted. Several overlapping factors, including individual variability, genetic and environmental factors, diagnostic delays and duration of gluten exposure, compliance with a gluten-free diet, lack of educational awareness, and complex immune-inflammatory interactions, were found to contribute to the overall incidence of CRC in CD patients. However, the true incidence may be underestimated due to the iceberg phenomenon, where limited clinical suspicion, poor screening, and underreporting may mask the underlying burden. This study highlights the need for increased clinical awareness and early screening, especially in noncompliant patients.