The overall goal of this study is to develop a platform for both large-scale chemoprevention trials and real-world chemoprevention studies for colorectal cancer (CRC) prevention. The specific objectives of this proof of concept study are to:

1. Evaluate the feasibility of a real-world chemoprevention agent (CPA) intervention (3-months of daily low-dose acetylsalicylic (ASA)) in participants at increased risk for CRC (one or more high-risk adenomas removed during colonoscopy) based on participant uptake, adherence (days taking CPA), and adverse events;
2. Evaluate factors related to uptake and adherence of ASA using validated surveys and interviews.

Study Design and Duration:

This is a single arm (non-randomized), open-label prospective cohort pilot study.

Screening Phase: up to 2 weeks Treatment Phase: 90 days Follow-up Phase: 90 days

Screening Phase: up to 14 days. Participants will consent to being enrolled in the study and to the use of ASA for a 90 day period. Regardless of agreement to use ASA for the entire study period, all participants will complete 6 baseline questionnaires.

Active Treatment Phase: up to 90 days. Participants that agree to the use of ASAs will be instructed to take daily ASAs for 90 days. Participants will be contacted by telephone at 1, 2, and 3 months to determine adverse events, adherence, and discontinuation. At 3 months participants will fill out a chemoprevention questionnaire and the Adherence Barriers Questionnaire (ABQ).

Follow-up Phase: 90 days. During the follow-up phase, participants will not be provided with ASA through the study nor will a specific recommendation be made to continue ASA. All participants will be contacted via telephone at the end of this period to determine the prevalence of continued use of ASA on their own.

Total study commitment will be up to 194 days. After consent, participants complete a 90 day active treatment phase followed by a 90 day follow-up phase. The trial is expected to be completed within one year.

Inclusion Criteria:

1. Men or women aged 50-59 at time of signing the informed consent

2. Documented history of high-risk adenomatous polyps diagnosed within the previous 12 months:

   1. At least one villous or tubulovillous polyp of any size
   2. At least one polyp with high-grade dysplasia of any size
   3. At least one adenomatous polyp ≥1 cm in size
   4. Three or more tubular adenomas <1 cm in size

3. Not currently using ASA for another condition

Exclusion Criteria:

1. Age < 50 or >= 60
2. Known allergy or hypersensitivity to ASA, salicylates or non-steroidal anti- inflammatory drugs.
3. Daily alcohol use > 3 units
4. Regular use of aspirin or non-steroidal anti-inflammatory drugs (> 2 dose/week)
5. Current use of corticosteroid (any dose) orally
6. Current use of methotrexate, valproic acid or digoxin
7. Currently taking any anti-cancer drug
8. Current use of anti-platelet agents or anticoagulants
9. Anticipated surgical procedure in the next 3 months
10. Current or past history of gastrointestinal ulcers
11. History of gastrointestinal bleeding (except hemorrhoidal or minor outlet type bleeding)
12. Known cirrhosis or hepatic impairment (for example, total bilirubin >1.25 Upper Limit of Normal, International Normalized Ratio >1.25)
13. Known bleeding disorder (hemorrhagic diathesis)
14. History of asthma or nasal polyps
15. History of colorectal cancer
16. Platelet count < 120 or > 450 (within previous 3 months)
17. Renal insufficiency (eGFR < 90 within previous 3 months)
18. History of congestive heart failure or left ventricular ejection fraction < 50 percent

Individual participant data will not be shared with researchers other than the Principal and Co-investigators. The results of this study will be published in a scientific peer reviewed journal. Both the chemoprevention intervention results and the feasibility results for scaling a chemoprevention program to all individuals attending a screening center will be presented. The qualified investigator holds the primary responsibility for publication of study results.