Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

Inclusion Criteria:

* Participants must have ulcerative colitis with \> 8 years history and clinical remission (including the clinical remission for an extraintestinal manifestation/complication) confirmed by yearly surveillance endoscopy examination (Mayo grading \< 3)
* They must be stable on maintenance therapy with mesalamine, thiopurines or biologics for over 3 months (Ulcerative Colitis Disease Activity Index \[UCDAI\] =\< 1)
* A history of segmental colon resection is allowed
* UC in clinical remission, but with dysplasia-associated lesion or mass (DALM) at entry endoscope examination and DALM was completely resected by endoscopic mucosa resection, is allowed
* Participants 18-70 years old (both men and women). This is the standard age range for routine ulcerative colitis surveillance in adults
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* White blood cell count within normal institutional limits or absolute neutrophil count \>= 1,500/uL
* Platelets \>= 100,000/uL
* Total bilirubin within normal institutional limits, unless known to have Gilberts syndrome
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (SGPT) =\< 1.5 X institutional upper limit of normal (ULN)
* Creatinine =\< 1.5 X institutional ULN
* Plasma level of cholesterol \< 240 mg/dl or LDL-C \< 190 mg/dl (since cholesterol \> 240 mg/dl and LDL-C \> 190 mg/dl need high dose (40 - 80 mg) atorvastatin per day to control hypercholesterolemia)
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
* Atorvastatin is contraindicated in pregnancy since it affects cholesterol synthesis pathway. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of baseline pregnancy test, throughout the duration of the study, and for 1 month following cessation of study drug. Females must begin adequate contraception immediately following screening pregnancy test. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If she is pregnant, she will be immediately withdrawn from the study and followed until the birth of the child
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Ulcerative proctitis (since patients with ulcerative proctitis have a significantly lower risk of developing colorectal cancer \[CRC\] than those with pancolitis or localized UC in left colon)
* Participants with medical conditions that, in the opinion of the investigator, would preclude the treatment intervention and colonoscopy, or limit ability to comply with therapy
* Participants with pancolitis or localized UC with total Mayo score \>= 3 including Mayo endoscopic sub-score \< 3 are excluded
* Use of corticosteroid therapy in the past 3 months due to high potential of relapse of active disease
* Use of statins in the last 12 months
* Use of any investigational drugs within the past 3 months
* A history of high-grade dysplasia or CRC or pan/severe colitis with total proctocolectomy
* History of chemotherapy within 2 years of screening
* History of allergic reactions attributed to atorvastatin
* Concomitant primary sclerosing cholangitis (PSC) with stage 4 liver fibrosis (biliary cirrhosis) and severe liver functional alteration
* Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or breastfeeding participants are excluded
* Human immunodeficiency virus (HIV)-positive participants are excluded due to anti-retroviral therapy that affect atorvastatin effect
* Children are excluded from this study since disease duration is usually \< 8 years and there is no data about p53 mutation in this patient population
* Current use of cyclosporine, fibrates (e.g., gemfibrozil, fenofibrate), strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, human immunodeficiency virus (HIV) protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, or cobicistat-containing products), or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort, bosentan, efavirenz, etravirine, modafinil, nafcillin)