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School of Public Health and South Carolina Cancer Center, University of South Carolina [W. Z., D-W. X., Q. D., X-O. S.], University of South Carolina School of Medicine and South Carolina Cancer Center [W-Q. W., X-O. S.], Columbia, South Carolina 29203, and Shanghai Cancer Institute, Shanghai 200032, China [F. J., J-R. C., Q. D., Y-T. G.]
Cytochrome P450–1B1 (CYP1B1) is a major enzyme catalyzing the formation
of genotoxic 4-hydroxyestradiol. This enzyme is also involved in the
activation of polycyclic aromatic hydrocarbons and heterocyclic
aromatic amines, mammary carcinogens in experimental animals. CYP1B1 is
genetically polymorphic, and the variations in the
CYP1B1 gene may be related to the risk of breast cancer.
We evaluated this hypothesis among 186 breast cancer cases and 200
age-matched controls as part of a large population-based case-control
study conducted in urban Shanghai during 1996 to 1998. Genomic DNA from
cases and controls was analyzed for genetic polymorphism in codon 432
(Val
Leu) of the CYP1B1 gene using a
PCR-RFLP-based assay. The frequency of the Leu allele
was 53% in cases and 46% in controls (P = 0.06).
Compared with those with the Val/Val genotype, women
with the Leu/Leu genotype had a 2.3-fold [95%
confidence interval (CI), 1.2–4.5] elevated risk of breast cancer
after adjusting for potential confounding variables. This positive
association was more pronounced among postmenopausal women (Odds ratio,
3.1; 95% CI, 1.0–9.1) than premenopausal women (OR, 1.9; 95% CI,
0.8–4.3). Elevated risks of breast cancer associated with homozygosity
for the Leu allele were observed in virtually all
subgroups of women defined by major risk factors for breast cancer. The
results from this study were consistent with recent findings from
in vitro and animal experiments implicating a
potentially important role of CYP1B1 in the etiology of human breast
cancer.
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