title: Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility.
abstract: BACKGROUND
  CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.
  
  
  METHODS
  We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls.
  
  
  RESULTS
  The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect.
  
  
  CONCLUSIONS
  Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trubicka
authors.forename: Ewa
authors.initials: E
authors.lastname: Grabowska-Kłujszo
authors.forename: Janina
authors.initials: J
authors.lastname: Suchy
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Masojć
authors.forename: Pablo
authors.initials: P
authors.lastname: Serrano-Fernandez
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Złowocka
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Banaszkiewicz
authors.forename: Rafał
authors.initials: R
authors.lastname: Wiśniowski
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kowalska
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1