title: Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation.
abstract: Clock genes are expressed in a self-perpetuating, circadian pattern in virtually every tissue including the human gastrointestinal tract. They coordinate cellular processes critical for tumor development, including cell proliferation, DNA damage response and apoptosis. Circadian rhythm disturbances have been associated with an increased risk for colon cancer and other cancers. This mechanism has not been elucidated, yet may involve dysregulation of the 'period' (PER) clock genes, which have tumor suppressor properties. A variable number tandem repeat (VNTR) in the PERIOD3 (PER3) gene has been associated with sleep disorders, differences in diurnal hormone secretion, and increased premenopausal breast cancer risk. Susceptibility related to PER3 has not been examined in conjunction with adenomatous polyps. This exploratory case-control study was the first to test the hypothesis that the 5-repeat PER3 VNTR sequence is associated with increased odds of adenoma formation. Information on demographics, medical history, occupation and lifestyle was collected prior to colonoscopy. Cases (n=49) were individuals with at least one histopathologically confirmed adenoma. Controls (n=97) included patients with normal findings or hyperplastic polyps not requiring enhanced surveillance. Unconditional multiple logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), after adjusting for potential confounding. Adenomas were detected in 34% of participants. Cases were more likely to possess the 5-repeat PER3 genotype relative to controls (4/5 OR, 2.1; 95% CI, 0.9-4.8; 5/5 OR, 5.1; 95% CI, 1.4-18.1; 4/5+5/5 OR, 2.5; 95% CI, 1.7-5.4). Examination of the Oncomine microarray database indicated lower PERIOD gene expression in adenomas relative to adjacent normal tissue. Results suggest a need for follow-up in a larger sample.
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Melannie
authors.initials: M
authors.lastname: Alexander
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Burch
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.affiliation: Center for Molecular Studies, Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Chen
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hurley
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Cavicchia
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Ray
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Shivappa
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Guess
authors.affiliation: Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Nursing and Health Innovation, and College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Youngstedt
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Creek
authors.affiliation: South Carolina Medical Endoscopy Center, and Department of Family Medicine, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lloyd
authors.affiliation: Medical Chronobiology Laboratory, Dorn Department of Veterans Affairs Medical Center, Columbia, SC, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Hébert
mesh_terms: D000236:Adenoma / Q000235:genetics*; D018256:Adenomatous Polyps / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics*; D004724:Endoscopy; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins