Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility.
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.
Trubicka
Joanna
J
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Grabowska-Kłujszo
Ewa
E
Suchy
Janina
J
Masojć
Bartłomiej
B
Serrano-Fernandez
Pablo
P
Kurzawski
Grzegorz
G
Cybulski
Cezary
C
Górski
Bohdan
B
Huzarski
Tomasz
T
Byrski
Tomasz
T
Gronwald
Jacek
J
Złowocka
Elzbieta
E
Kładny
Józef
J
Banaszkiewicz
Zbigniew
Z
Wiśniowski
Rafał
R
Kowalska
Elzbieta
E
Lubinski
Jan
J
Scott
Rodney J
RJ
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
D004273:DNA, Neoplasm; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1