Abstract

BACKGROUNDIndividuals with Lynch syndrome (LS) and hereditary non-polyposis colorectal cancer (HNPCC) are at increased risk of both colorectal cancer and other cancers. The interplay between immunosuppression, a comorbid inflammatory condition (CID), and HNPCC on cancer risk is unclear. AIMTo evaluate the impact of CIDs, and exposure to monoclonal antibodies and immunomodulators, on cancer risk in individuals with HNPCC.METHODSIndividuals prospectively followed in a hereditary cancer registry with LS/HNPCC with the diagnosis of inflammatory bowel disease or rheumatic disease were identified. We compared the proportion of patients with cancer in LS/HNPCC group with and without a CID. We also compared the proportion of patients who developed cancer following a CID diagnosis based upon exposure to immunosuppressive medications. RESULTSA total of 21 patients with LS/HNPCC and a CID were compared to 43 patients with LS/HNPCC but no CID. Cancer occurred in 84.2% with a CID compared to 76.7% without a CID (P = 0.74) with no difference in age at first cancer diagnosis 45.5 ± 14.6 vs 43.8 ± 7.1 years (P = 0.67). LS specific cancers were diagnosed in 52.4% with a CID vs 44.2% without a CID (P = 0.54). Nine of 21 (42.9%) patients were exposed to biologics or immunomodulators for the treatment of their CID. Cancer after diagnosis of CID was seen in 7 (77.8%) of exposed individuals vs 5 (41.7%) individuals unexposed to biologics/immunomodulators (P = 0.18). All 7 exposed compared to 3/5 unexposed developed a LS specific cancer. The exposed and unexposed groups were followed for a median 10 years and 8.5 years, respectively. The hazard ratio for cancer with medication exposure was 1.59 (P = 0.43, 95%CI: 0.5-5.1). CONCLUSIONIn patients with LS/HNPCC, the presence of a concurrent inflammatory condition, or use of immunosuppressive medication to treat the inflammatory condition, might not increase the rate of cancer occurrence in this limited study.

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