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Investigating the Association Between Lynch Syndrome and the Prevalence of Autoimmune Disorders

Miikeda, Aika (2022) Investigating the Association Between Lynch Syndrome and the Prevalence of Autoimmune Disorders. Master's Thesis, University of Pittsburgh. (Unpublished)

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Background: Lynch syndrome is caused by germline pathogenic variants in one of the mismatch repair (MMR) genes. It contributes to a significant portion of MMR deficient tumors, which are more susceptible to immune checkpoint inhibitors compared to MMR proficient tumors. MMR deficiency leads to high levels of microsatellite instability as insertion/deletion mutations are accumulated in microsatellites, leading to neoantigen production, which triggers immune responses. T-cell responses towards these neoantigens have been observed in the peripheral blood of individuals with Lynch syndrome without tumor development. These data suggest that having a germline MMR mutation may elicit an immune response, raising the question of whether patients with Lynch syndrome may be at a higher risk of developing autoimmune disorders.
Methods: The study included 312 patients diagnosed with Lynch syndrome who are enrolled in the UPMC Hereditary Colorectal and Associated Tumor Registry. A retrospective chart review investigated the presence of 30 autoimmune disorders in these patients. The prevalence of each autoimmune disorder was compared to that of the general population. Chi-square tests were performed on demographic/cancer data and two-sided exact binomial tests were used to assess the significance of prevalence data.
Results: Out of 312 patients, 35 individuals were identified to have autoimmune disorders, including 10 out of 30 autoimmune conditions assessed. Most of the identified autoimmune disorders did not show significant differences in their prevalence compared to the general population. The prevalence of inflammatory bowel disease (IBD), however, was 1.92% in this study compared to 0.48% in the general population (p=0.004237).
Conclusion: This study suggests that patients with Lynch syndrome may have higher rates of IBD, but do not seem to have significantly higher frequencies of other autoimmune disorders. Future studies should involve larger sample sizes to conduct further statistical analyses on the cancer risks in patients with Lynch syndrome with autoimmune disorders and explore potential mechanisms of an IBD overrepresentation in patients with Lynch syndrome.
Public Health Significance: Our investigation may contribute to the scientific community by providing knowledge that is yet to be explored and will potentially inform care and management for patients with Lynch syndrome and their providers.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Miikeda, Aikaaim33@pitt.eduaim33
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairYurkovich,
Committee MemberDurst, Andreaadurst@pitt.eduadurst
Committee MemberBrand,
Committee MemberDomsic, Robynrtd4@pitt.edurtd4
Date: 1 July 2022
Date Type: Publication
Defense Date: 10 June 2022
Approval Date: 1 July 2022
Submission Date: 24 June 2022
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 68
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Lynch Syndrome Autoimmune disorders Inflammatory Bowel Disease
Date Deposited: 01 Jul 2022 18:56
Last Modified: 01 Jul 2023 05:15


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