Enhanced mRNA Expression of Colonic IL-6 in Cronkhite-Canada Syndrome Bearing Colorectal Cancer

Immunosuppressive and nutritional treatments have improved the prognosis of Cronkhite-Canada syndrome (CCS). CCS-associated polyps are benign and categorized into hamartomatous, inflammatory, hyperplastic, and adenomatous polyps; however, the development of gastrointestinal cancer is considered the most significant prognostic factor for CCS. Although the adenoma-carcinoma sequence and inflammation-associated carcinogenesis are two major pathways for the development of colorectal cancers (CRCs), it remains largely unknown which pathway plays critical roles in the development of CRCs in CCS. Inflammation-associated carcinogenesis might be involved in the development of CRCs associated with CCS because CCS-associated polyps are characterized by submucosal infiltration of immune cells. Given the fact that proinflammatory cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α underlie the pathogenesis of inflammation-associated carcinogenesis, we examined the involvement of proinflammatory cytokines in the transformation of CCS-associated polyps into CRCs.

Three cases of CCS were enrolled: two cases with concurrent CRCs and a single case without CRC. mRNA was isolated from non-cancerous CCS-associated polyps and subjected to reverse transcription quantitative polymerase chain reaction to determine expression of proinflammatory cytokines. Colonic biopsy samples were isolated from non-tumor portions of patients with colonic adenoma to determine mRNA expression of proinflammatory cytokines in healthy colonic mucosa.

Higher mRNA expression of IL-6, but not IL-1β or TNF-α, in non-cancerous CCS-associated polyps was observed in two patients with CCS and concurrent CRCs as compared with four healthy colonic mucosal samples and a patient with CCS without CRC.

IL-6-mediated inflammation-associated carcinogenesis might be involved in the transformation of CCS-associated polyps into CRC.