Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

Inclusion Criteria: * Participants with LS defined as one of the following: * Mutation positive: MLH1, MSH2/EPCAM and MSH6 genotypes with prior history of ≥1 colorectal neoplasms\*\* (tubular or tubulovillous adenoma\[s\] or sessile serrated polyps/adenomas/lesion\[s\] or traditional serrated adenoma\[s\]), and/or colorectal cancer\[s\] (but no active cancer for 6 months) OR * PMS2 genotype with prior history of colon cancer(s) (but no active cancer for 6 months) * Note: Should be confirmed by pathology report or letter from endoscopist to participant * Participants must have at least part of the descending/sigmoid colon and/or rectum intact * Participants must be at least 6 months from any cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy or radiation). Ongoing adjuvant endocrine therapy is allowed * Participants \>= 18 years will be enrolled. Because the risk of LS related cancers is very low in participants \< 18 years of age, children and adolescents are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Leukocytes \>= 3,000/microliter * Absolute neutrophil count \>= 1,500/microliter * Platelets \>= 100,000/microliter * Total bilirubin =\< institutional upper limit of normal * Note: Higher bilirubin levels (\<= 3 mg/dL) can be allowed if due to a known benign liver condition, i.e. Gilbert's * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transamin…