Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers

Inclusion Criteria:

1. Male or female patients ≥ 18 years.
2. Confirmed germline pathological variant in one of the mismatch repair genes; MSH2, MLH1, PMS2 or MSH6 or a 3' EPCAM deletion associated with MSH2 silencing or be a carriers of a constitutional epimutation manifesting a classic Lynch syndrome phenotype.
3. Able to swallow tablets.
4. Provision of voluntary written informed consent.

Exclusion Criteria:

1. Regular use of a non-steroidal anti-inflammatory agent (except aspirin\*) on a prescription and/or long-term basis. Regular is defined as \> 3 doses per week.
2. Regular use of aspirin (\> 3 doses per week or on a prescription basis) that cannot be replaced with any one of the randomised arms of the study followed by 100mg dose.
3. Current methotrexate use at a weekly dose of ≥ 15mg.
4. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
5. Existing clinically significant liver impairment.
6. Existing renal failure.
7. Confirmed active peptic ulcer disease within the previous three months.
8. Known bleeding diathesis or concomitant warfarin therapy.
9. Inability to comply with study procedures and agents.
10. Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years.
11. Women who are breastfeeding.
12. Any significant medical illness that would interfere with study participation.

    * Previous use of aspirin for medicinal purposes does not exclude enrolment but duration and quantity need to be documented in detail