Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2022; 13(1): 49-61
Published online Jan 24, 2022. doi: 10.5306/wjco.v13.i1.49
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, JP Achkar, Matthew Kalady, JM Church, Gautam Mankaney
Muhammad S Faisal, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Carol A Burke, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
David Liska, Amy L Lightner, Margaret O’Malley, Lisa LaGuardia, JM Church, Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States
Brandie Leach, Center for Personalized Genetic Healthcare, Genomic Medicine Institute, Cleveland, OH 44195, United States
Benjamin Click, Department of Gastroenterology, Hepatology, & Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
JP Achkar, Center for Inflammatory Bowel Disease, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
Matthew Kalady, Department of Colorectal Surgery, Ohio State University, Columbus, OH 43210, United States
Gautam Mankaney, Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
Author contributions: Burke CA, Liska D, Lightner A, Kalady M and Church J provided original data as well as reviewed and edited the manuscript; Faisal MS collected variables and analyzed data; Leach B, O'Malley M and LaGuardia L provided technical support, data variables, and reviewed the manuscript; Click B, Achkar JP, Burke CA and Mnakaney G designed the study, supervised and edited the final version; Faisal MS and Mankaney G envisioned the study, wrote the final manuscript.
Institutional review board statement: This study was approved by Cleveland Clinic Institutional Review Board (IRB 2884).
Informed consent statement: This study was exempt from signed consent form requirements.
Conflict-of-interest statement: Authors have no conflicts of interest to disclose.
Data sharing statement: Consent was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Gautam Mankaney, MD, Doctor, Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, 1100 Ninth Avenue C3-GAS, Seattle, WA 98101, United States. mankaneg@gmail.com
Received: April 9, 2021
Peer-review started: April 9, 2021
First decision: July 27, 2021
Revised: August 11, 2021
Accepted: December 22, 2021
Article in press: December 22, 2021
Published online: January 24, 2022
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: Lynch syndrome, Hereditary non-polyposis colorectal cancer, Inflammatory bowel disease, Immunosuppression, Biologics

Core Tip: Individuals with hereditary non-polyposis colorectal cancer (HNPCC) are at increased risk of both colorectal cancer and other cancers. When they have a comorbid inflammatory condition (CID) that requires immunosuppression, clinicians may be hesitant to prescribe these medications due to concern of an elevated cancer risk. We show that individuals with HNPCC and CID have a similar cancer risk to those with HNPCC alone, and that the addition of immunosuppression does not increase overall cancer risk, but may increase the risk of LS-specific cancers.