title: Case-control study of candidate gene methylation and adenomatous polyp formation.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70-90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation.
  
  
  METHODS
  Patients recruited from a local endoscopy clinic provided informed consent and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios (ORs) and 95 % confidence intervals (95% CIs) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders.
  
  
  RESULTS
  Complete data were available for 107 participants; 36 % had adenomas (men 40 %, women 31 %). Hypomethylation of the MINT1 locus (OR 5.3, 95% CI 1.0-28.2) and the PER1 (OR 2.9, 95% CI 1.1-7.7) and PER3 (OR 11.6, 95% CI 1.6-78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71-97 %), sensitivity was relatively low (18-45 %).
  
  
  CONCLUSIONS
  Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance.
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.
authors: M
authors: http://orcid.org/0000-0003-4261-6543
authors: M
authors: Alexander
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA. burch@mailbox.sc.edu.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA. burch@mailbox.sc.edu.|William Jennings Bryant Dorn Department of Veterans Affairs Medical Center, Columbia, SC, USA. burch@mailbox.sc.edu.
authors: J B
authors: JB
authors: Burch
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.
authors: S E
authors: SE
authors: Steck
authors: Center for Molecular Studies, Greenwood Genetic Center, Greenwood, SC, USA.
authors: C-F
authors: CF
authors: Chen
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors: T G
authors: TG
authors: Hurley
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.|Division of Community Health Promotion, Florida Department of Health, Tallahassee, FL, USA.
authors: P
authors: P
authors: Cavicchia
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.
authors: N
authors: N
authors: Shivappa
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.
authors: J
authors: J
authors: Guess
authors: Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA.
authors: H
authors: H
authors: Zhang
authors: College of Nursing and Health Innovation, College of Health Solutions, Arizona State University and Phoenix VA Health Care System, Phoenix, AZ, USA.
authors: S D
authors: SD
authors: Youngstedt
authors: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors: K E
authors: KE
authors: Creek
authors: South Carolina Medical Endoscopy Center, and Department of Family Medicine, University of South Carolina School of Medicine, Columbia, SC, USA.
authors: S
authors: S
authors: Lloyd
authors: Center for Molecular Studies, Greenwood Genetic Center, Greenwood, SC, USA.
authors: K
authors: K
authors: Jones
authors: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.|Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.|Department of Family and Preventive Medicine, School of Medicine, University of South Carolin, Columbia, SC, USA.
authors: J R
authors: JR
authors: Hébert
mesh_terms: D018256:Adenomatous Polyps / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011401:Promoter Regions, Genetic / Q000235:genetics
keywords: Adenomatous polyp; Circadian rhythm; Colorectal cancer; Screening tests