Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome

Muhammad S Faisal; Carol A Burke; David Liska; Amy L Lightner; Brandie Leach; Margaret O'Malley; Lisa LaGuardia; Benjamin Click; J P Achkar; Matthew Kalady; J M Church; Gautam Mankaney

doi:10.5306/wjco.v13.i1.49

Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome

World J Clin Oncol. 2022 Jan 24;13(1):49-61. doi: 10.5306/wjco.v13.i1.49.

Authors

Affiliations

¹ Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States.
² Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
³ Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States.
⁴ Center for Personalized Genetic Healthcare, Genomic Medicine Institute, Cleveland, OH 44195, United States.
⁵ Department of Gastroenterology, Hepatology, & Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States.
⁶ Center for Inflammatory Bowel Disease, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States.
⁷ Department of Colorectal Surgery, Ohio State University, Columbus, OH 43210, United States.
⁸ Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, Seattle, WA 98101, United States. mankaneg@gmail.com.

Abstract

Background: Individuals 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.

Aim: To evaluate the impact of CIDs, and exposure to monoclonal antibodies and immunomodulators, on cancer risk in individuals with HNPCC.

Methods: Individuals 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.

Results: A 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).

Conclusion: In 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.

Keywords: Biologics; Hereditary non-polyposis colorectal cancer; Immunosuppression; Inflammatory bowel disease; Lynch syndrome.