Characteristics and Prognosis of Colorectal Cancer Associated With Rheumatic Disease

It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression.Key words: Colorectal cancer, Rheumatic disease, Host immunity, PrognosisIt is well known that host immunity plays an important role in defenses against the development and progression of cancer. The degree of lymphocyte infiltration into tumors has been reported to correlate with improvements of patient survival.¹ In carcinogen-induced mouse models of cancer, primary tumor susceptibility has been found to be enhanced in immunocompromised mice; conversely, the capacity for such tumors to grow after transplantation into wild-type mice is reduced.^2,3 Although cancer cells originate from autologous normal tissue, the immune system can recognize even minimal cellular alterations, distinguish cancerous from normal cells, and elicit an immune response.In autoimmune diseases represented by rheumatic disease (RD), the immune system loses the ability to distinguish nonself from self, eliciting an immune response against self-antigens; in this process, there is a possibility that immune defenses against non-normal cells are lost or impaired, facilitating the development and progression of cancer. In addition, the development of RD associated with cancer has been reported, and as its development is dependent on the production of substances such as hormones, peptides, autocrine and paracrine mediators, and antibodies or the stimulation of cytotoxic lymphocytes, the condition is known as paraneoplastic rheumatic syndrome. In such cases, RD tends to be less responsive to therapy than its nonparaneoplastic equivalents, and instead, treatment of the underlying cancer usually results in regression of RD.^4,5 Thus, it is postulated that RD and cancer are closely associated. However, only a few reports on the incidence and risk of cancer among patients with RD exist,^6,7 and the characteristics and prognosis of colorectal cancer (CRC) in these patients remain to be elucidated.In the present study, we investigated the development of CRC in the background of an immunologic disorder caused by RD, with the hypothesis that patients with CRC and autoimmune diseases such as RD will have a poorer prognosis than those without RD, as a result of depressed antitumor immunity caused by immune system incompetence. Thus, we aimed to clarify the features and prognosis of CRC-associated RD, and for this purpose, we compared the clinicopathologic features of patients with CRC with or without underlying RD.