Cytochrome P450 1B1 Val432Leu polymorphism and breast cancer risk in Nigerian women: a case control study.
BACKGROUND
Cytochrome P450 1B1 (CYP1B1) is active in the metabolism of estrogens to reactive catechols and of different procarcinogens. Several studies have investigated the relationship between genetic polymorphisms of CYP1B1 and breast cancer risk with inconsistent results. A G --> C transversion polymorphism in the heme-binding region in codon 432 of the gene results in amino acid change (Val --> Leu); the Leu allele display increased catalytic efficiency for 4-hydroxylation of estradiol in some experimental systems.


METHODS
In this study, we utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to assess the relationship between this polymorphism and breast cancer risk in a case control study including 250 women with breast cancer and 250 controls from four University Teaching Hospitals in Southern Nigeria.


RESULTS
Heterozygosity for the CYP1B1 M1 genotype (CYP1B1 M1 [Val/Leu]) was associated with a significant 59% increased risk of breast cancer (OR = 1.59, 95% CI 1.01-2.58) while homozygosity for the genotype (CYP1B1 M1 [Leu/Leu]) conferred a non-significant 51% increased risk of breast cancer. These risk profiles were modified in subgroup analysis. In premenopausal women, harboring at least one CYP1B1 (Leu) allele conferred a significant two-fold increased risk of breast cancer (OR = 2.04, 95% CI 1.10-3.78). No significant association was observed in postmenopausal women (OR = 1.08, 95% CI 0.57-2.04).


CONCLUSIONS
Our results suggest that the codon 432 polymorphism of the CYP1B1 gene is associated with increased risk of breast cancer and is particularly involved in breast cancer risk in premenopausal women of African descent.
Okobia
Michael N
MN
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. michaelokobia@yahoo.com
Bunker
Clareann H
CH
Garte
Seymour J
SJ
Zmuda
Joseph M
JM
Ezeome
Emmanuel R
ER
Anyanwu
Stanley Nc
SN
Uche
Emmanuel Eo
EE
Osime
Usifo
U
Ojukwu
Joseph
J
Kuller
Lewis H
LH
Ferrell
Robert E
RE
Taioli
Emanuela
E