Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk.
BACKGROUND
Cytochrome P450 (CYP) enzymes have the potential to affect colorectal cancer (CRC) risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones.


METHODS
To investigate if common variants of CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1 and CYP19A1 influence CRC risk we genotyped 2,575 CRC cases and 2,707 controls for 20 single nucleotide polymorphisms (SNPs) that have not previously been shown to have functional consequence within these genes.


RESULTS
There was a suggestion of increased risk, albeit insignificant after correction for multiple testing, of CRC for individuals homozygous for CYP1B1 rs162558 and heterozygous for CYP1A2 rs2069522 (odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.03-1.80 and OR = 1.34, 95% CI: 1.00-1.79 respectively).


CONCLUSIONS
This study provides some support for polymorphic variation in CYP1A2 and CYP1B1 playing a role in CRC susceptibility.
Bethke
Lara
L
Section of Cancer Genetics, Institute of Cancer Research, Surrey, UK. lara.bethke@icr.ac.uk <lara.bethke@icr.ac.uk>
Webb
Emily
E
Sellick
Gabrielle
G
Rudd
Matthew
M
Penegar
Stephen
S
Withey
Laura
L
Qureshi
Mobshra
M
Houlston
Richard
R
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D003577:Cytochrome P-450 Enzyme System