Use of aspirin for chemoprevention in Lynch syndrome: A systematic review and meta-analysis.

Document Type

Abstract

Publication Date

6-1-2025

Abstract

Background: Lynch syndrome is the most common hereditary colorectal cancer (CRC) that is caused by germline mutations in mismatch repair genes. Previous studies have reported variable results regarding the role of aspirin as a chemopreventive agent in patients with hereditary colon cancer like Lynch syndrome. With this meta-analysis, we aimed to identify whether aspirin reduces the incidence of CRC in patients with Lynch syndrome. Methods: Following PRISMA guidelines, a systematic literature search was conducted in Pubmed, Embase and Clinicaltrials.gov from the date of inception to December 31, 2024 focusing on the use of aspirin in Lynch sydrome. After removing duplicates, 911 studies were primarily screened and the secondary screening yielded 4 studies, including one randomized controlled trial(RCT) and three cohort studies. Meta-analysis was performed for the calculation of Risk Ratio with 95% Confidence Interval utilizing Inverse Variance Random Effects model using Review Manager (version 5.4.1). Results: A total of 3437 patients with Lynch syndrome were included from all four studies with the mean age being 44 years and female gender being 56.4% (n = 1938). The most common mutations identified were MLH1 (39.4%) and MSH2 (39.3%). Former or current smoking was reported in 45% patients (n = 1157/2576). Patients who had aspirin exposure were 736 and patients without aspirin use were 2701. Out of 3437 patients, the total CRC cases reported were 1124 (32.7%). CRC was reported in 201 patients (27.3%) who used aspirin, compared to 923 patients(34%) who did not use aspirin. The risk ratio for CRC development in patients with use of aspirin, irrespective of duration, compared to patients without aspirin use was 1.16 [95% CI 0.79-1.70, Chi2= 26.38, p< 0.00001, I2 = 89%], which shows no significant reduction in CRC with aspirin use. In addition, the risk ratio when aspirin use of at least 2 years was compared with non-aspirin users was 0.97 [95%CI 0.73-1.28, Chi2= 4.44, p = 0.11, I2= 55%], which shows no significant statistical difference between the two groups. Conclusions: Current National Comprehensive Cancer Network guidelines suggest considering the use of aspirin in Lynch syndrome based on evidence from the RCT that was included in our review. However, real-world application of aspirin remains limited due to a variety of factors, including uncertainty of its effectiveness and concern for potential side effects. Our study did not show a statistically significant benefit of aspirin use on development of CRC in Lynch syndrome patients possibly due to short duration of follow up and presence of confounding factors between CRC and non-CRC groups. Further well-designed RCTs are needed to address this gap.

Publication Title

Journal of Clinical Oncology

Volume

43

Issue

16 Supplement

First Page

e15725

Last Page

e15725

Comments

2025 ASCO Annual Meeting I held 2025-05-30 to 2025-06-03 in Chicago, IL

Link to Full Text

Open Access

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