Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation

Melanie Alexander, James B. Burch, Susan E. Steck, Chin Fu Chen, Thomas G. Hurley, Philip Cavicchia, Meredith Ray, Nitin Shivappa, Jaclyn Gues, Hongmei Zhang, Shawn Youngstedt, Kim E. Crek, Stephen Lloyd, Xiaoming Yang, James R. Hébert

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)935-941
Number of pages7
JournalOncology Reports
Volume33
Issue number2
DOIs
StatePublished - Dec 1 2015

Fingerprint

Adenoma
Case-Control Studies
Odds Ratio
Confidence Intervals
Minisatellite Repeats
Genes
Adenomatous Polyps
Neoplasms
Tandem Repeat Sequences
Colonoscopy
Circadian Rhythm
Polyps
Occupations
Colonic Neoplasms
DNA Damage
Gastrointestinal Tract
Life Style
Logistic Models
Genotype
Cell Proliferation

Keywords

  • Adenoma
  • Circadian rhythm
  • Clock gene
  • Colorectal cancer
  • Variable number tandem repeat

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Alexander, M., Burch, J. B., Steck, S. E., Chen, C. F., Hurley, T. G., Cavicchia, P., ... Hébert, J. R. (2015). Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation. Oncology Reports, 33(2), 935-941. https://doi.org/10.3892/or.2014.3667

Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation. / Alexander, Melanie; Burch, James B.; Steck, Susan E.; Chen, Chin Fu; Hurley, Thomas G.; Cavicchia, Philip; Ray, Meredith; Shivappa, Nitin; Gues, Jaclyn; Zhang, Hongmei; Youngstedt, Shawn; Crek, Kim E.; Lloyd, Stephen; Yang, Xiaoming; Hébert, James R.

In: Oncology Reports, Vol. 33, No. 2, 01.12.2015, p. 935-941.

Research output: Contribution to journalArticle

Alexander, M, Burch, JB, Steck, SE, Chen, CF, Hurley, TG, Cavicchia, P, Ray, M, Shivappa, N, Gues, J, Zhang, H, Youngstedt, S, Crek, KE, Lloyd, S, Yang, X & Hébert, JR 2015, 'Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation', Oncology Reports, vol. 33, no. 2, pp. 935-941. https://doi.org/10.3892/or.2014.3667
Alexander M, Burch JB, Steck SE, Chen CF, Hurley TG, Cavicchia P et al. Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation. Oncology Reports. 2015 Dec 1;33(2):935-941. https://doi.org/10.3892/or.2014.3667
Alexander, Melanie ; Burch, James B. ; Steck, Susan E. ; Chen, Chin Fu ; Hurley, Thomas G. ; Cavicchia, Philip ; Ray, Meredith ; Shivappa, Nitin ; Gues, Jaclyn ; Zhang, Hongmei ; Youngstedt, Shawn ; Crek, Kim E. ; Lloyd, Stephen ; Yang, Xiaoming ; Hébert, James R. / Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation. In: Oncology Reports. 2015 ; Vol. 33, No. 2. pp. 935-941.
@article{c95d5cf012434cdba8d5ca215c840a4c,
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.",
keywords = "Adenoma, Circadian rhythm, Clock gene, Colorectal cancer, Variable number tandem repeat",
author = "Melanie Alexander and Burch, {James B.} and Steck, {Susan E.} and Chen, {Chin Fu} and Hurley, {Thomas G.} and Philip Cavicchia and Meredith Ray and Nitin Shivappa and Jaclyn Gues and Hongmei Zhang and Shawn Youngstedt and Crek, {Kim E.} and Stephen Lloyd and Xiaoming Yang and H{\'e}bert, {James R.}",
year = "2015",
month = "12",
day = "1",
doi = "10.3892/or.2014.3667",
language = "English (US)",
volume = "33",
pages = "935--941",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "2",

}

TY - JOUR

T1 - Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation

AU - Alexander, Melanie

AU - Burch, James B.

AU - Steck, Susan E.

AU - Chen, Chin Fu

AU - Hurley, Thomas G.

AU - Cavicchia, Philip

AU - Ray, Meredith

AU - Shivappa, Nitin

AU - Gues, Jaclyn

AU - Zhang, Hongmei

AU - Youngstedt, Shawn

AU - Crek, Kim E.

AU - Lloyd, Stephen

AU - Yang, Xiaoming

AU - Hébert, James R.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Adenoma

KW - Circadian rhythm

KW - Clock gene

KW - Colorectal cancer

KW - Variable number tandem repeat

UR - http://www.scopus.com/inward/record.url?scp=84919459650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919459650&partnerID=8YFLogxK

U2 - 10.3892/or.2014.3667

DO - 10.3892/or.2014.3667

M3 - Article

C2 - 25501848

AN - SCOPUS:84919459650

VL - 33

SP - 935

EP - 941

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 2

ER -