To learn about the effects of naproxen and aspirin on the normal colon in people with Lynch Syndrome.
"Mutation-Positive Lynch syndrome": carriers or obligate carriers (by pedigree) of a pathogenic mutation in one of the DNA mismatch repair (MMR) genes (i.e., MLH1, MSH2/EPCAM, MSH6, or PMS2).
"Mutation-Negative Lynch syndrome": patients with a personal history of a non-sporadic MMR deficient premalignant lesion (i.e., polyp) or a non-sporadic MMR deficient malignant tumor (where "non-sporadic MMR deficient" is defined by: microsatellite-instability high by either immunohistochemistry or MSI testing or both, but no evidence of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, and/or no evidence of BRAF mutation in cases with loss of both MLH1 and PMS2) but germline MMR genetic testing showed either a variant of unknown significance or mutation negative result or had declined germline MMR genetic test-ing.
Participants must not have evidence of active/recurrent malignant disease for 6 months.
Participants must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation).
Individuals with presence of two somatic mutations/loss of heterozygosity (LOH) in one of the four MMR genes (MLH1, MSH2, MSH6, and PMS2) in MMR-deficient neoplasm (defined as a tumor with MSI-H by PCR analysis or loss of staining in one of the four MMR proteins).
Individuals who received scheduled NSAIDs or COX-inhibitors of any kind for >3 days during anytime within the 2 weeks prior to baseline eligibility screening visit. By exception, individuals receiving cardio-protective aspirin (e.g., 81 mg PO daily) will be eligible provided they are will-ing to stop no less than 7 days prior to starting on naproxen or aspirin in this study.
Individuals who are status post total proctocolectomy (i.e., removal of all colon and rectum).
Individuals with active gastroduodenal ulcer disease in the preceding 5 years.
M.D. Anderson Cancer Center
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Cancer Institute (NCI)
Collaborator