Polymorphisms in the CYP1A1 gene are associated with prostate cancer risk.
CYP1A1 is likely to play an important role in the etiology of CaP through its function in activating environmental procarcinogens and catalyzing the oxidative metabolites of estrogens. To test the hypothesis that genetic polymorphisms in the CYP1A1 gene may be associated with the risk for CaP, we compared the allele, genotype and haplotype frequencies of 3 SNPs (3801T>C, 2455A>G and 2453C>A) of CYP1A1 among 159 HPC probands, 245 sporadic CaP cases and 222 unaffected men. Two SNPs (3801T>C and 2455A>G) were each individually associated with CaP risk when the allele and genotype frequencies were compared between CaP patients and unaffected controls. Furthermore, a combined SNP analysis using a haplotype approach revealed an even stronger association in Caucasians. Specifically, 4 major haplotypes (T-A-C, C-A-C, C-G-C and T-A-A) accounted for 99.8% of all observed haplotypes. These 4 haplotypes correspond to the previously described nomenclature (CYP1A1*1A, CYP1A1*2A, CYP1A1*2B and CYP1A1*4). The frequencies of these 4 haplotypes were significantly different among CaP patients and controls. The haplotype T-A-C (CYP1A1*1A) was significantly associated with increased risk for CaP, and the haplotype C-A-C (CYP1A1*2A) was significantly associated with decreased risk for CaP. These findings suggest that genetic polymorphisms in CYP1A1 may modify the risk for CaP.
Chang
Bao-li
BL
Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
Zheng
Siqun L
SL
Isaacs
Sarah D
SD
Turner
Aubrey
A
Hawkins
Gregory A
GA
Wiley
Kathy E
KE
Bleecker
Eugene R
ER
Walsh
Patrick C
PC
Meyers
Deborah A
DA
Isaacs
William B
WB
Xu
Jianfeng
J
D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D004247:DNA; D019363:Cytochrome P-450 CYP1A1