title: Association of the clock genes polymorphisms with colorectal cancer susceptibility.
abstract: OBJECTIVE
  The circadian rhythm regulates the cell cycle progression and DNA damage response. The aim of our study was to investigate the association between polymorphisms in the CLOCK1, PER2, and PER3 genes with the colorectal cancer (CRC) susceptibility and clinicopathological variables.
  
  
  METHODS
  Four hundred two CRC patients and 480 healthy controls were included in a case-control study. Genotype and allelic frequencies of 311T>C (rs1801260) in CLOCK1 gene, G3853A (rs934945) in PER2 gene and 4/5 repeats polymorphisms in PER3 gene were evaluated by the polymerase chain reaction (PCR) restriction fragment length polymorphism method in the DNA extracted from the peripheral blood of patients and controls.
  
  
  RESULTS
  The frequencies of the 311T>C CLOCK1 gene, CC genotype and C allele were significantly higher among CRC patients compared to controls (P < 0.0001) elevating the CRC risk by 2.78- and 1.78-fold respectively. No correlation was found between G3853A and 4/5 repeats polymorphisms and CRC risk. The C/G/5 and C/G/4 repeats haplotypes were higher in CRC patients (P = 0.0009 and P = 0.038) elevating the CRC risk by 60% and 89% respectively. No correlation was found between any polymorphism and clinicopathological characteristics of CRC patients.
  
  
  CONCLUSIONS
  The 311T>C polymorphism in the CLOCK1 gene significantly increases the risk for CRC development while it does not affect the outcome of CRC patients.
authors.affiliation: First Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Karantanos
authors.forename: George
authors.initials: G
authors.lastname: Theodoropoulos
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.forename: Anna
authors.initials: A
authors.lastname: Vaiopoulou
authors.forename: Christina
authors.initials: C
authors.lastname: Karantanou
authors.forename: Dimitrios J
authors.initials: DJ
authors.lastname: Stravopodis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Bramis
authors.forename: Maria
authors.initials: M
authors.lastname: Lymperi
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pektasidis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056926:CLOCK Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D056950:Period Circadian Proteins / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: C421902:PER2 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: circadian genes; colorectal cancer; polymorphisms