title: The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer.
abstract: Cytochrome P450 1B1 (CYP1B1) is a major enzyme in the initial catabolic step of estradiol (E2) metabolism and belongs to the multitude of genes regulated by the estrogen receptor alpha (ERalpha). The common non-synonymous polymorphisms CYP1B1_1358_A>G and CYP1B1_1294_C>G increase CYP1B1 enzymatic activity. Given a relationship between CYP1B1 and breast tumor E2 level as well as E2 level and breast tumor ERalpha expression it is of interest to know whether CYP1B1 polymorphisms have an impact on the ERalpha status of breast cancer. We genotyped the GENICA population-based breast cancer case-control collection (1,021 cases, 1,015 controls) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and investigated in cases the association between genotypes and tumor ERalpha status (739 ERalpha positive cases; 212 ERalpha negative cases) by logistic regression. We observed a significant association between the homozygous variant CYP1B1_1358_GG genotype and negative ERalpha status (P = 0.005; OR 2.82, 95% CI: 1.37-5.82) with a highly significant Ptrend for CYP1B1_1358_A>G and negative ERalpha status (P = 0.003). We also observed an association of CYP1B1_1358_GG and negative PR status (P = 0.015; OR 2.36, 95% CI: 1.18-4.70) and a Ptrend of 0.111 for CYP1B1_1358_A>G and negative progesterone receptor (PR) status. We conclude that the CYP1B1_1358_A>G polymorphism has an impact on ERalpha status in breast cancer in that the CYP1B1_1358_GG genotype known to encode higher CYP1B1 activity is associated with ERalpha negativity.
authors.affiliation: Molecular Mechanisms of Origin and Treatment of Breast Cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376, Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Christiane B
authors.initials: CB
authors.lastname: Pierl
authors.forename: Susanne
authors.initials: S
authors.lastname: Haas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Caren
authors.initials: C
authors.lastname: Vollmert
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dippon
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1