S0205 Association of Cancer With Comorbid Inflammatory Diseases in Lynch Syndrome and Lynch-Like Syndrome Individuals

Abstract

INTRODUCTION: Individuals with Lynch syndrome (LS) and Lynch-Like Syndrome (LLS) develop microsatellite unstable colorectal tumors that produce neo-antigens. Neo-antigens are highly immunogenic, resulting in enhanced immune surveillance of tumors. The impact of inflammatory, auto-immune conditions on cancer in these patients is not known. We compared the cancer incidence in patients with and without comorbid inflammatory diseases (CID). METHODS: Patients with LS (pathogenic variant in a mismatch repair gene), or LLS (Amsterdam positive family history with MSI-H tumor) from a hereditary cancer registry undergoing surveillance were identified. Those with a CID disease (IBD/rheumatic disease) based on ICD-10 criteria were selected and considered “cases”. LS and LLS patients without a comorbid inflammatory disease were matched for age, gender, and genetic mutation in a 2:1 ratio and considered “controls”. We compared proportion of patients with cancer at the time of last follow up visit between the two groups. RESULTS: 21 patients with LS/LLS and CID were compared to 43 controls. Mean age for cases was 53.9 ± 15.7 yrs compared to controls 53.8 ± 7.8 yrs. There was no major difference in race, sex, smoking and family history between the two groups (Table 1). Colonoscopies per yr following LS/LLS diagnosis was 0.89 in cases compared to 0.86 in controls (P = 0.86). 76.2% cases vs 53.5% controls had a history of complete or partial colectomy. 83% of female cases compared to 76% of female controls had a TAH-BSO prophylactically or for endometrial cancer. Mean age at CID diagnosis was 38.9 ± 13.4 yrs. Diseases included: Crohn’s 5 (23.8%), ulcerative colitis 2 (9.5%), inflammatory/rheumatoid arthritis 7(33.3%), psoriatic arthritis 1(4.8), psoriasis 3(14.3%), and one case each of dermatomyositis, ankylosing spondylitis, and sarcoidosis. 84.2% cases developed any cancer compared to 76.7% in controls (P = 0.74). Age at 1st cancer diagnosis was 45.5 ± 14.6 yrs in cases and 43.8 ± 7.1 yrs in controls (P = 0.67). Cancer incidence after CID diagnosis was 57.1% in cases with median 10(6.0-16.5) yr follow-up versus 46.5% in controls (P = 0.42) when followed for 10 yrs prior to their last follow up or death. Most of these were LS specific cancers: 52.4% of cases vs 44.2% of controls (P = 0.54).Table 1Table 2Figure 3CONCLUSION: Our data does not demonstrate substantially different incidence rates of cancer between LS/LLS patients with and without comorbid inflammatory disease.