TY - JOUR
T1 - Cytochrome P450 1B1 Val432Leu polymorphism and breast cancer risk in Nigerian women
T2 - A case control study
AU - Okobia, Michael N.
AU - Bunker, Clareann H.
AU - Garte, Seymour J.
AU - Zmuda, Joseph M.
AU - Ezeome, Emmanuel R.
AU - Anyanwu, Stanley N.C.
AU - Uche, Emmanuel E.O.
AU - Osime, Usifo
AU - Ojukwu, Joseph
AU - Kuller, Lewis H.
AU - Ferrell, Robert E.
AU - Taioli, Emanuela
N1 - Funding Information:
Please address correspondence to: Barbara Russo, Centre Médical Universitaire (CMU), Rue Michel-Servet, Genève 1206, Switzerland. E-mail: [email protected] Competing interests: M. Matucci Cerinic has received fees from the boards of MSD, Biogen, Lilly, Pfizer, BMS, Janssen and Actelion; consultation fees from Chemomab and grants from MSD. C. Bruni has received consultancy fees from Actelion, Eli Lilly; grants from Gruppo Italiano Lotta alla Sclerodermia (GILS), Fondazione Italiana Ricerca sull’Artrite (FIRA), European Scleroderma Trial and Research (EUSTAR), Foundation for Research in Rheumatology (FOREUM), Italian Society for Rheumatology (SIR), outside the submitted work. The other co-authors have declared no competing interests.
PY - 2009
Y1 - 2009
N2 - 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). Conclusion. 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.
AB - 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). Conclusion. 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.
UR - http://www.scopus.com/inward/record.url?scp=60349095031&partnerID=8YFLogxK
U2 - 10.1186/1750-9378-4-S1-S12
DO - 10.1186/1750-9378-4-S1-S12
M3 - Article
AN - SCOPUS:60349095031
SN - 1750-9378
VL - 4
JO - Infectious Agents and Cancer
JF - Infectious Agents and Cancer
IS - SUPPL. 1
M1 - S12
ER -